Transplantation Proceedings

Editorial Board

2010-01-01

Long-Term Outcomes of Short Bowel Syndrome Requiring Long-Term/Home Intravenous Nutrition Compared in Children With Gastroschisis and Those With Volvulus

D. Sala, S. Chomto, S. Hill — 2010-01-01

Abstract: Introduction: Short bowel syndrome (SBS) is a malabsorptive state that occurs following extensive small intestinal resection. The most severely affected children require intravenous feeding/parenteral nutrition (PN). Two common causes in infancy/early childhood are intestinal resection for volvulus and resection of necrotic small intestine in infants with gastroschisis. The aim of this study was to review the long-term outcomes of children with severe intestinal failure who remained dependent on PN for many months or years. We evaluated the outcomes among gastroschisis cases versus those following resection of mid-gut volvulus or congenital short gut.Methods: We reviewed the case records over a 10-year period from 1997 of children presenting by 5 years of age with volvulus and/or congenital short gut or gastroschisis and who were dependent on long-term/home PN. We obtained data regarding the diagnosis, the small intestinal length, the presence of the ileo-cecal valve, the survivals, and the incidences of weaning from PN.Results: Six children underwent resection following volvulus or congenital short gut syndromes and 7 had gastroschisis. Ten of the 13 children underwent surgery as neonates and 3 from 2–5 years of age. The residual small intestinal length was <10 cm in 1, 10–25 cm in 4, 25–50 cm in 5, 50–100 cm in 2, and >100 cm in 1 case. The ileo-cecal valve was removed in 8 children. All children were treated with PN after surgery for at least 7 months. All 7 children with gastroschisis and 1 with <10 cm small intestine after intestinal resection for volvulus still required PN after 14–120 months. Three with gastroschisis died. All 5 children with volvulus and >10 cm small intestine were weaned from PN, thriving at our review 7 months–7 years later.Conclusions: Infants and young children with short gut and >10 cm small intestine gain intestinal autonomy. In contrast, those with gastroschisis have poor outcomes and should be referred for intestinal transplantation assessment more readily than those with after intestinal resection for volvulus short gut.

Chronic Intestinal Pseudo-Obstruction Related to Viral Infections

2010-01-01

Abstract: Chronic intestinal pseudo-obstruction (CIPO), one of the most severe gastrointestinal motility disorders, is a condition characterized by a clinical picture mimicking small bowel occlusion with related symptoms and signs in the absence of demonstrable mechanical obstruction. Analysis of full-thickness biopsy samples may unravel structural changes of the neuromuscular layer involving the whole gut, although the midgut is usually worst affected. Intestinal pseudo-obstruction can occur in association with systemic neurological, endocrine, and connective tissue diseases or malignancy but, when no recognizable etiology is found, CIPO is referred to as idiopathic (CIIPO). The latter form can be diagnosed early in life due to a genetic etiology or in adulthood when a viral origin may be considered. This review addresses the hypothesis that some systemic neurotrophic viral infections can affect the enteric nervous system thereby altering normal peristaltic activity. Available data are reviewed, focusing specifically on herpesviruses or polyomaviruses (JC virus). These suggest that in comparison to a proportion of CIIPO patients, healthy controls rarely harbor viral DNA in the myenteric plexus, leaving open the possibility that a viral infection might have an etiologic role in the development of CIIPO. The review thus provides some new perspectives in the pathophysiology and perhaps targeted treatment of CIIPO.

Natural History of Intestinal Failure Induced by Chronic Idiopathic Intestinal Pseudo-Obstruction

2010-01-01

Abstract: Chronic intestinal pseudo-obstruction is a severe, often unrecognized disease characterized by disabling and potentially life-threatening complications over time. The diagnosis is based on the evidence of typical clinical manifestations, radiological evidence of distended bowel loops with air-fluid levels, and the exclusion of any organic obstruction of the gut lumen. The radiological sign of intestinal occlusion allows the distinction from enteric dysmotility, which is characterized by better outcomes. Manometry can play a supportive role in defining the diagnosis, and differences in the manometric pattern of chronic intestinal pseudo-obstruction and enteric dysmotility have been shown. The disease is often unrecognized, and the diagnosis, therefore, delayed by several years. Thus, the majority of patients undergo useless and potentially dangerous surgeries. Long-term outcomes are generally poor despite surgical and medical therapies characterized by disabling and potentially life-threatening complications over time. A substantial percentage of patients requires parenteral nutrition. Failure of this nutritional support represents an indication for small bowel transplantation.

Cambridge-Miami Score for Intestinal Transplantation Preoperative Risk Assessment: Initial Development and Validation

2010-01-01

Abstract: Introduction: Preoperative quantification of survival after transplantation would assist in assessing patients. We have developed a preliminary preoperative scoring system, called the Cambridge-Miami (CaMi) score, for transplantation of the small intestine either alone or as a composite graft.Methods: The score combines putative risk factors for early-, medium-, and long-term survival. Factors included were loss of venous access and impairment of organs or systems not corrected by transplantation. Each factor was scored 0–3. A score of 3 indicated comorbidity approaching a contraindication for transplantation, that which might lead to but was not currently an adverse risk factor scored 1, and that presenting a definite but moderate increase in risk scored 2. The preoperative scores of 20 patients who had received intestinal transplants either isolated or as part of a cluster graft, who had either been followed up postoperatively for at least 10 years, or died within 10 years were compared with their survivals.Results: Postoperative survival and CaMi score inversely correlated when analysed using Spearman test (rs = −0.82; P = .0001). A score of <3 associated with survival ≥3 years (12/12 patients) and >3 with survival of <6 months (4/4). Patient Kaplan-Meier (KM) survival curves for patients grouped according to CaMi score became significantly different from group 0 to group 3. Using this as a threshold score patients grouped as either >2 or <3 had significantly different survival rates (log-rank; P = .0001), KM median survival hazard ratio (HR) = 6, and rate of death KM HR = 5. Receiver-operator characteristics indicate a high degree of accuracy for prediction of death with an area under the curve (C statistic) at 3 years of 0.98, at 5 years of 0.82, and at 10 years of 0.65.Conclusion: This initial validation suggested that the preoperative CaMi score predicted postoperative survival.

Review of the Diagnoses Predisposing Infants to Intestinal Failure on Hospitalized Parenteral Nutrition

J. Pichler, V. Horn, S. MacDonald, S. Hill — 2010-01-01

Abstract: During the last 3 decades the use of parenteral nutrition (PN) and the aggressive introduction of enteral feeding in daily practice have transformed the outcome for even the sickest of these infants. More than 90% of infants and children now survive after extensive small bowel resection in the neonatal period. During the last 3 decades the use of parenteral nutrition (PN) and the aggressive introduction of enteral feeding in daily practice have transformed the outcome for even the sickest of these children. The aim of this study was to review the diagnoses (other than infants purely premature) that predispose infants to intestinal failure (IF) and dependency on PN as well as their outcomes. A total of 63 children less than 1 year old received PN for more than 28 days including 35 (56%) boys; 29% of cases were preterm infants with a median gestational age of 26.5 weeks (range, 24–33 weeks). The median age at the start of PN was 0.25 years or 3 months. Median duration of PN treatment was 62 days and median duration of hospitalization was 128 days. Twenty-three (36.5%) children had a primary nondigestive disorder (PNDD) and 40 (63.5%), a primary digestive disorder (PDD). Forty (63.5%) children with severe intestinal failure were successfully weaned off PN; whereas 8 (13%) infants with severe gastrointestinal diseases remained dependent on IV nutrition. Fourteen (22%) patients died. Infants less than 1 year of age with severe intestinal failure have up to a 75% survival rate, with a 65% chance of achieving intestinal autonomy. For children presenting with PDD in infancy, there is a high risk of needing long-term PN.

Sepsis and Its Etiology Among Hospitalized Children Less Than 1 Year of Age With Intestinal Failure on Parenteral Nutrition

J. Pichler, V. Horn, S. MacDonald, S. Hill — 2010-01-01

Abstract: Infections accompany intestinal failure (IF) more commonly in children than in adults, with reported incidences of 2% to 29%. Appropriate care of the central venous catheter is the most important factor preventing infections; but in addition, bacteria translocate from the dysmotile gut as a possible source of septicemia. The aim of this retrospective analysis was to investigate the rate and the epidemiologic profile of septicemia in the patient group at greatest risk, namely, children less than 1 year of age with IF on parenteral nutrition (PN). Among 63 children less than 1 year of age who were included over a 2-year period, 55% were boys. The overall median age at the start of PN was 0.3 years, with a mean duration of 80 days. Some 68% of patients had at least one episode of septicemia, experiencing a mean of 1.5 episodes (range, 1–12). Also, 19% of children displayed polymicrobial bloodstream infections. The most common Gram-positive pathogens were Staphylococcus spp and Enterococcus spp; the Gram-negative pathogens were Klebsiella spp followed by Enterobacter spp and E. coli.Infants less than 1 year of age with IF >28 days experienced a high (68%) rate of sepsis. There was no difference in the incidence of catheter-related blood stream infection according to the primary underlying diagnosis. The most common pathogens were Staphylococcus spp and Enterococcus spp, similar to etiologies of sepsis among children in intensive care units.

Preliminary Experience With Alemtuzumab Induction Therapy Combined With Maintenance Low-Dose Tacrolimus Monotherapy in Small-Bowel Transplantation in China

L. Yuan-Xin, L. Ning, L. You-Sheng, N. Xiao-Dong, L. Ming, W. Jian, L. Jie-Shou — 2010-01-01

Abstract: Introduction: The goal of combining alemtuzumab induction therapy with low-dose tacrolimus monotherapy in small-bowel transplantation (SBTx) is to enable improved graft acceptance without immunologic unresponsiveness caused by stronger immunosuppression regimens. Herein, we report preliminary experience using this protocol in 5 patients who underwent SBTx in China.Methods: Patients received methylprednisolone sodium succinate (Solu-Medrol), 1 g, followed by alemtuzumab infusion, 30 mg, during SBTx and another gram of prednisolone before reperfusion. Tacrolimus monotherapy without steroid was used for maintenance immunosuppression. Tacrolimus trough levels were 10 to 15 ng/dL during the first 3 months, and weaned to 5 to 10 ng/mL after 3 months.Results: Three recipients have survived for longer than 1 year; 1 patient is currently alive at 9 months, and another at 5 months post-SBTx. Grafts in these 5 recipients achieved excellent function, and in all patients, total parenteral nutrition was discontinued at 2 to 3 weeks postoperatively and normal oral intake was resumed. One recipient died at 13 months post-SBTx of severe rejection; the condition of the other 4 recipients who were still alive was good. Pathologic analysis of ileoscopic biopsy specimens revealed 4 episodes of indeterminate to mild acute cellular rejection (ACR) at 1 to 3 months, 3 episodes of indeterminate to mild ACR at 4 to 6 months, 3 episodes of moderate ACR at 7 to 12 months, and 1 episode of severe ACR at 13 months. All episodes of indeterminate to moderate ACR were totally resolved; only treatment of severe ACR failed. One patient experienced an episode of invasive fungal infection and another episode of cytomegaloviral infection, with total recovery after treatment.Conclusions: Our preliminary experience in these 5 cases showed that the protocol combining alemtuzumab induction therapy with low-dose tacrolimus monotherapy without maintenance steroid therapy past-SBTx can effectively control rejection with excellent graft function. Nevertheless, close surveillance of ACR should be still performed after 6 months.

Daclizumab and Alemtuzumab as Induction Agents in Adult Intestinal and Multivisceral Transplantation: Rejection and Infection Rates in 40 Recipients During the Early Postoperative Period

2010-01-01

Abstract: Background: Allograft rejection in intestinal transplantation occurs frequently, and bacterial, fungal, and viral infections related to strong immunosuppression regimens remain an important complication posttransplantation. Induction therapy has enabled improvement in graft and patient survival rates.Objectives: In analyze the effects of daclizumab and alemtuzumab as induction therapies on inflections complications and incidence of acute cellular rejection (ACR) during the early posttransplantation period.Patients and Methods: Between December 2000 and August 2009, we performed 43 intestinal transplantation procedures in 42 adult recipients (median [SD] age, 34.8 [9.5] years; male-female ratio, 22:20; isolated or multivisceral graft, 32/11), and compared findings during the first 30 days posttransplantation in 40 recipients. Patients were divided into 2 groups: 12 treated with daclizumab (Zenapax; Hoffman-La Roche Ltd, Basel, Switzerland): 8 isolated intestinal grafts and 4 multivisceral grafts) and 28 treated with alemtuzumab (Campath-1H: 22 isolated intestinal grafts and 6 multivisceral grafts). Maintenance immunosuppression was based on tacrolimus and steroids in the first group and low-dose tacrolimus in the second group.Results: During the first month posttransplantation, 8 daclizumab recipients (66.6%) experienced 9 episodes of mild ACR, which were successfully treated with steroid therapy, and 8 patients (66.6%) developed a bacterial infection requiring treatment. Fourteen episodes of ACR occurred in 12 alemtuzumab recipients (42.8%): 11 mild, 1 mild to moderate, and 2 moderate; 16 patients (57.1%) required treatment for infections. Five-year patient cumulative survival was 66% in daclizumab recipients and 43% in alemtuzumab recipients. Five-year graft survivals was 66% in daclizumab recipients and 41% in alemtuzumab recipients. In both groups, P was not statistically significative.Conclusions: The infection rate is considerably high with both protocols. Alemtuzumab seems to offer better immunosuppression against ACRs during the first month posttransplantation.

Comprehensive Surgical Intestinal Rescue and Transplantation Program in Adult Patients: Bologna Experience

2010-01-01

Abstract: Introduction: Surgical approaches to complicated benign intestinal failure are accepted worldwide, especially in the pediatric population. Intestinal transplant surgery is thought to rescue patients in whom complications of total parenteral nutrition (TPN) develop.Objective: To report our experience with surgical intestinal rescue in an adult population with intestinal failure.Patients and Methods: An intestinal rehabilitation program initiated at our institution included comprehensive medical rehabilitation, surgical bowel rescue, and transplantation. From 2000 to 2009, of 81 adult patients referred by our gastroenterologists for bowel rehabilitation, 42 (51,8%) underwent 43 transplantations (32 isolated intestinal grafts and 11 multivisceral grafts). Underlying diseases were primarily short-bowel syndrome, Gardner syndrome, and intestinal pseudo-obstruction. Thirty-nine patients (48,2%) underwent surgical rescue (40 cases) consisting of bowel resection, adhesiolysis, stricturoplasty, liver transplantation with portocaval hemitransposition (6 cases in 5 patients). Underlying diseases were primarily intestinal fistulas, stenosis, or perforations, short-bowel syndrome, cocoon syndrome, and complete portal thrombosis.Results: After a mean (SD) follow-up of 1043 (1016) days, in the transplantation population, 21 patients (50%) are alive, with a 1-, 3-, 5-year patient survival of 76%, 59%, and 52%, respectively, and graft survival of 66%, 54%, and 48%, respectively. After 901 (404) days in the rescue population, 32 patients (82%) are alive (2 died, and 5 were lost to follow-up); in 75%, TPN 25% was discontinued, and are receiving oral feeding with TPN support. The 1- and 3-year survival rate was 100% and 83%, respectively.Conclusions: Deaths occurred primarily in the transplantation population. Intestinal surgical rescue, when possible, is optimal.

Psychological Adaptation and Quality of Life of Adult Intestinal Transplant Recipients: University of Bologna Experience

2010-01-01

Abstract: Introduction: Intestinal transplantation has become an accepted therapy for individuals permanently dependent on total parenteral nutrition (TPN) with life-threatening complications. Quality of life and psychological well-being can be seen as important outcome measures of transplantation surgery.Methods: We evaluated 24 adult intestinal transplant recipients and 24 healthy subjects (a control group). All subjects were administered the Italian Version of the Psychological Well-Being Scales (PWB) by C. Ryff, the World Health Organization Quality of Life-Brief (WHOQOL), and the Symptom Questionnaire (SQ) by R. Kellner and G.A. Fava, a symptomatology scale. Quality of life and psychological well-being were assessed in transplant recipients in relationship to the number of rejections, the number of admissions, and the immunosuppressive protocol.Results: Intestinal transplant recipients reported significantly higher scores in the “personal growth” category (P = .036) and lower scores in the “positive relation with others” (P = .013) and “autonomy” (P = .007) dimensions of PWB, compared with the controls. In the WHOQOL, the scores of transplant recipients were lower only in the psychological domain (P = .011). Transplant recipients reported significantly higher scores in the “somatic symptom” (P = .027) and “hostility” (P = .018) dimensions of the SQ, compared with the controls. Transplant recipients with number of admissions >8 reported higher scores in “anxiety” (P = .019) and “depression” (P = .021) scales of the SQ, and the patients with a Daclizumab protocol reported higher scores in “depression” (P = .000) and “somatic symptom” (P = .008) of the SQ. There were no significant differences regarding number of rejections and socio-demographic variables.Conclusion: Improvement of psychological well-being in the transplant population may be related to the achievement of the goal of transplantation: recovery of bowel function. But the data confirmed that the transplant experience required a long and difficult adaptation trial to the new condition of “transplant recipient.”

International Grading Scheme for Acute Cellular Rejection in Small-Bowel Transplantation: Single-Center Experience

2010-01-01

Abstract: A standardized grading scheme for the assessment of acute cellular rejection (ACR) in small-intestine transplantation was proposed in 2003 at the Eighth International Small Intestinal Transplantation Symposium. We have implemented the current grading scheme for ACR in small-bowel transplantation since October 2003. The pathologic diagnoses of those small-intestine biopsy samples, including ACR grade and other supplementary findings were evaluated. A total of 3484 small intestine biopsy samples from 155 patients were available for evaluation in this study. Frequency of grades 0, indeterminate, 1, 2, and 3 acute cellular rejection was 33.9%, 49.1%, 12.6%, 3.7%, and 0.8%, respectively. Duration of ACR episode strongly correlated with grade of ACR episode (P < .001). Other supplementary findings included acute vascular rejection component, 2.2%; increase in lymphoplasmacytic infiltrate in lamina propria, 15.7%; mucosal fibrosis, 0.4%; and regenerative changes, 0.3%. Our data substantiate that this grading system is reliable and useful for clinical decision making in bowel transplantation. We suggest that an assessment and quantification of supplementary findings be considered a component of the International Pathology Grading Scheme.

Citrulline Evaluation in Bowel Transplantation

2010-01-01

Abstract: Introduction: The purpose of this study was to evaluate the correlation of plasma citrulline and rejection episodes in intestinal transplantation.Methods: From January 2007 until present, we performed citrulline assays on our small bowel patients. We investigated the correlation of these assays with the rejection status of the patients. The rejection status of the graft was defined based on graft biopsies.Results: Of 5195 citrulline samples, average serum citrulline levels decreased significantly when the patients presented a rejection episode. We found the following: no rejection, 17.38 μm/L; mild rejection, 13.05 μm/L; moderate rejection, 7.98 μm/L; and severe rejection, 6.05 μm/L. Our current emphasis is to determine the predictive power of citrulline with other biomarkers versus as a separate and isolated measurement.Conclusions: In our study, citrulline levels correlated significantly with the rejection status of the graft. Serial follow-up of the patients using this assay may alert us to the possibility of increased alloreactivity and rejection episodes.

Evaluation of Calprotectin Level in Intestinal Content as an Early Marker for Graft Rejection

2010-01-01

Abstract: Introduction: The diagnosis of rejection after intestinal transplantation is still performed by endoscopic biopsy monitoring. Less invasive diagnostic procedures are desirable, although they are not available so far. Calprotectin, a stable cytosolic granulocyte protein, which previously was used as a marker of inflammatory processes, has been proposed to be a biochemical marker for rejection. The aim of the present work was to analyze the concordance between calprotectin levels in intestinal content and the presence of graft rejection after small bowel transplantation.Methods: Calprotectin level was measured using a commercial ELISA kit on 137 samples of intestinal content randomly collected during endoscopies performed on 11 intestinal transplantation patients during 2 years' follow-up. Calprotectin determinations were correlated with histological and clinical findings. The cut-off level was determined retrospectively by receiver-operator curve analysis.Results: Based on histological findings and clinical records, samples were discerned as rejection positive (37 of 137), versus negative (35 of 137) samples or those with no clinical, endoscopic, or histological findings (65 of 137 samples). A cut-off value of 65 μg of calprotectin/g of intestinal content provided the best assay parameter according to the clinical findings: a 76% sensitivity and a 47% specificity. False positive results corresponded to patients with gastrointestinal infections (13%), systemic infections (13%), ulcers (10%), or nonspecific histological alterations of the mucosa (15%). The other false positive cases corresponded to postsurgical samples (4%), or patients with concomitant gastrointestinal symptoms (2%). Most false negative results (78%) were observed during recovery from severe acute rejection episodes, among successfully treated patients. In these cases, epithelial reconstitution and no mucosal infiltration was observed. If the latter group were discarded, sensitivity rose to 93%, and specificity, to 50% with a 96% negative predictive value. Furthermore, a weak correlation was observed between calprotectin levels and the severity of rejection.Conclusions: This study confirmed the results obtained by other groups: fecal calprotectin dosage showed a good sensitivity but low specificity for the diagnosis of intestinal rejection because high calprotectin levels can also be observed in other clinical conditions. Nevertheless, it might be used as a first line for continuous evaluation of intestinal transplantation status, like other biochemical parameters that are used in kidney or liver transplantation, before considering the need for a biopsy.

Gene Expression Profiling of MicroRNAs in Small-Bowel Transplantation Paraffin-Embedded Mucosal Biopsy Tissue

2010-01-01

Abstract: Background: The molecular mechanisms and regulation of immune-mediated rejection of organ allografts remains unclear. Recent studies have reported that small non-coding RNAs, microRNAs (miRNAs) play a critical role in the immune system via modulation of transcription and translation.Purpose: We hypothesized that particular miRNAs provide regulation of an ensuing intragraft immune effector response. The aim of our study was to detect miRNAs involved in acute cellular rejection (AR) in human small intestinal allografts.Materials: We examined 12 small intestinal mucosal biopsies (AR, 7 cases, all grade 2 or 3) and non-rejecting (NR) allografts (5 cases, all grade 0) obtained from recipients after small bowel or multivisceral transplantation. RNA was isolated from the formalin-fixed paraffin-embedded (FFPE) biopsy samples and transcribed to cDNA. After preamplification we utilized a PCR based TaqMan Low Density Array (TLDA) containing 365 mature human miRNAs. Relative quantification was done based on pooled normal intestine using a comparative Ct method.Results: We identified 62 miRNA upregulated genes in small bowels with ACR, and 35 were downregulated. Forty-two miRNA genes were upregulated in non-ACR small bowel biopsy samples (grade IND), and 45 were downregulated. The relative fold change ratio of ACR to non-ACR was calculated, and 50 upregulated and 8 downregulated miRNAs were detected as significant. Several interesting miRNAs will be evaluated further from this preliminary study. Our data suggests that intragraft miRNAs are potentially involved in the activation of a host alloimmune response to donor. These miRNAs may serve as targets for appropriate intervention and may be useful to monitor the allograft status.

Monitoring Cytomegalovirus T-Cell Immunity in Small Bowel/Multivisceral Transplant Recipients

2010-01-01

Abstract: Background: Cytomegalovirus (CMV) is a major cause of graft failure and posttransplantation mortality in intestinal/multivisceral transplantation. CMV infection exhibits a wide range of clinical manifestations from asymptomatic infection to severe CMV disease.Study's Purpose: The purposes of this study were to assess the utility of measuring CMV-specific cellular immunity in bowel/multivisceral transplant recipients and to provide additional information on the risk of infection and development of CMV disease.Methods: We studied 10 bowel/multivisceral transplant recipients to investigate the kinetics of CMV infection using real-time polymerase chain reaction (on blood and biopsy tissue samples) and CMV-specific T-cell reconstitution by Enzyme-linked ImmunoSPOT Assay (ELISPOT) that enumerates Interferon-γ–secreting CMV-specific T cells upon in vitro stimulation with viral antigens (pp65 and IE-1).Results: All patients were seropositive for CMV. According to the pattern of T-cell reconstitution occurring either within the first month after transplantation or later, patients were classified as early (n = 7) or late responders (n = 3). Clinically, early responder patients (3/7; 43%) experienced asymptomatic or mild CMV infections, whereas all late responders (3/3; 100%) developed moderate or severe CMV disease. A reduction in mean and peak CMV viral load was observed in early responders, whereas the onset time of infection did not differ significantly between early and late CMV responders.Conclusions: A good and early reconstitution of CMV-specific T-cell immune responses after transplantation is a critical determinant in controlling CMV infections. Simultaneous monitoring of CMV infection and CMV-specific T-cell immunity predicts T-cell–mediated control of CMV infection.

Early and Late Virological Monitoring of Cytomegalovirus, Epstein-Barr Virus, and Human Herpes Virus 6 Infections in Small Bowel/Multivisceral Transplant Recipients

2010-01-01

Abstract: Background: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the major causes of graft failure and posttransplantation mortality among small bowel and multivisceral transplantations (SB/MVT). Little is known about human herpes virus 6 (HHV-6) infections in transplant recipients.Study Purpose: The purposes of this study were to analyze the clinical relevance of CMV, EBV, and HHV-6 infections after small bowel transplantation and to establish whether routine monitoring for HHV-6 infection should be recommended for the prevention of severe complications in this population.Methods: Ten adult patients were monitored based on CMV, EBV, and HHV6 DNA quantifications in blood and biopsy tissue samples. Three patients were monitored for at least 5 months (early period) and 7 patients were monitored for 1 to 5 years after transplantation (late period).Results: In the early period, despite prophylaxis all 3 patients developed symptomatic CMV infections: 1 fever/diarrhea, 1 enteritis and rejection, as well as 1 fever and pneumonia. Only 1 patient developed EBV and HHV-6 infections. The average time of onset of CMV infection was 3 months after transplantation and only 24 days for HHV6 infection. In the late period, of the 7 SB/MVT recipients only 1 developed an EBV infection at 2 years after transplantation. No CMV or HHV-6 infections were identified in any patient.Conclusions: CMV infection is a major cause of organ disease and rejection in the early period after transplantation. EBV infection in adult recipients must be considered also in the late period, particularly in association with severe immunosuppression. Because HHV-6 infection occurs earlier than CMV/EBV, it may serve as an indicator for more intense virological surveillance.

Thrombotic Microangiopathy Following Intestinal Transplantation: A Single Center Experience

2010-01-01

Abstract: Background: Transplant-related thrombotic microangiopathy (TMA) is a well-recognized complication of all types of transplantations. Despite its known relationship with immunosuppressive therapy, only a few cases have been reported following intestinal transplantation.Methods: We retrospectively reviewed the medical files of nine consecutive intestinal transplant patients between 2000 and 2008.Results: The diagnosis of TMA was established in 3 patients (33%). At diagnosis the immunosuppressive therapy consisted of tacrolimus (n = 3), combined with azathioprine (n = 1) or sirolimus (n = 2) and steroids (n = 2). The median time between transplantation and TMA was 104 days (range, 55–167 days). Levels of ADAMTS13, a von Willebrand protease, were within normal ranges in all 3 patients. Treatment consisted of stopping/tapering of tacrolimus, together with initiation of plasma therapy, leading to complete remission in all 3 patients. During further follow-up, all 3 patients showed severe graft rejection necessitating more profound immunosuppressive therapy, leading to graft loss in 1 patient and infection-related death in the 2 others. At a median follow-up of 52 months (range, 9–100 months) all remaining TMA-free patients (n = 6) were alive with functioning grafts under minimal immunosuppression.Conclusion: Herein we have described 3 intestinal transplant patients who were diagnosed with transplantation-related TMA. Despite excellent disease control the final outcomes were dismal, which clearly contrasts with the outcome among TMA-free patients, who were all well with functioning grafts at last follow-up.

Mycophenolate Mofetil–Related Gastrointestinal Mucosal Injury in Multivisceral Transplantation

2010-01-01

Abstract: Mycophenolate mofetil (MMF) has become an important and commonly used drug for maintenance immunosuppression therapy in recipients of all types of organ transplants. The drug is an antimetabolite that blocks the de novo pathway of purine synthesis. Although it selectively inhibits B- and T-lymphocyte proliferation, enterocytes are partially susceptible to MMF. One of the main limitations of this drug is gastrointestinal toxicity, with diarrhea the most frequently reported adverse effect. Most studies of MMF-associated gastrointestinal toxicity have been performed in patients with solid-organ transplants, although no data on changes related to MMF toxicity in bowel allografts have been published in the English literature. We evaluated mucosal intestinal biopsy tissue from patients with multivisceral transplants receiving MMF therapy. Our objective was to find morphologic changes that might be attributed to MMF toxicity, as well as changes that could differentiate MMF toxicity from acute rejection. Examination of the surface epithelium, lamina propria, and crypts in this small group of patients showed no specific changes that could be associated with MMF toxicity. Changes such as graft-vs-host disease or inflammatory bowel disease described in previous studies of solid-organ transplantation were not observed. Larger studies and the use of special stains and new markers might be necessary to characterize possible patterns of MMF toxicity and their differences from acute rejection.

Evaluation of Hemodynamic, Metabolic, and Electrolytic Changes After Graft Reperfusion in a Porcine Model of Intestinal Transplantation

R.M. de Oliveira Clark, A. Bakonyi Neto, E.H. Bianchi, L.R. de Carvalho — 2010-01-01

Abstract: Background: We sought to establish an anesthetic protocol to evaluate the hemodynamic, metabolic, and electrolytic changes after graft reperfusion in pigs undergoing orthotopic intestinal transplant (ITx).Methods: Fifteen pigs were distributed into two groups: GI (n = 6), without immunosuppression, and GII (n = 9), immunosuppressed before surgery with tacrolimus (0.3 mg/kg). The animals were premedicated at 1 hour before surgery with IM acepromazine (0.1 mg/kg), morphine (0.4 mg/kg), ketamine (10 mg/kg), and atropine (0.044 mg/kg IM). Anesthesia induction used equal proportions of diazepam and ketamine (0.1–0.15 mL/kg/IV) and for maintenance in IV infusion of xylazine (1 mg/mL), ketamine (2 mg/mL), and guaiacol glyceryl ether 5% (50 mg/mL), diluted in 250 mL of 5% glucose solution. In addition, recipient pigs were treated with isofluorane inhalation. Heart rate (HR), systolic (SAP), mean (MAP), and diastolic (DAP) arterial pressure, pulse oximetry, respiratory frequency (f), capnography, body temperature (T), blood gas analysis (pH, Paco2, Pao2, base excess, BE; Hco3−, Sato2), serum potassium (K), calcium (Ca), sodium, hematocrit (Hct), and glucose (Glu) were measured at four times; M0: after incision (basal value); M1: 10 minutes before reperfusion; and M2 and M3: 10 and 20 minutes after graft reperfusion.Results: All groups behaved in a similar pattern. There was significant hypotension after graft reperfusion in GI and GII (M2 = 56.2 ± 6.4 and M3 = 57.2 ± 8.3 mm Hg and M2 = 65.7 ± 10.2 and M3 = 67.8 ± 16.8 mm Hg, respectively), accompanied by elevated HR. The ETco2 was elevated at M2 (42 mm Hg) and M3 (40 mm Hg). Metabolic acidosis was observed after reperfusion, with significant increase in K levels.Conclusion: The anesthetic protocol for donors and recipients was safe to perform the procedure, allowing control of hemodynamic and metabolic changes after reperfusion without differences regarding immunosuppression.

Immediate Antibody-Mediated (Hyperacute) Rejection in Small-Bowel Transplantation and Relationship to Cross-Match Status and Donor-Specific C4d-Binding Antibodies: Case Report

2010-01-01

Abstract: Background: The role of preformed donor-specific antibodies (DSAs) as a barrier to isolated intestinal transplantation (ITx) remains ambiguous; thus, a positive cross-match has not been a contraindication to ITx.Objective: To report the case of a patient with Crohn's disease who underwent ITx and developed immediate antibody-mediated rejection on reperfusion of the allograft.Methods: Percent reactive antibody testing was performed using pretransplantation serum samples and at transplantation using bead-based assays (Luminex, Luminex Corp, Austin, Tex) and flow cytometry solid-phase assays (FlowPRA single-antigen beads (One Lambda, Inc, Canoga Park, Calif). Serologic tests, flow cytometry cross-matching, and flow cytometry assays of C4d-binding serum antibodies were also performed. Histologic and immunofluorescent analysis of biopsy specimens was performed.Results: HLA typing revealed no sharing of class I or II antigens between donor and recipient. Pretransplantation donor-specific antibodies (DSA) were present at transplantation. Cross-matching (performed during surgery) was positive for class I and II by serologic testing and flow cytometry. After reperfusion, the graft immediately developed severe ischemic injury and arteritis on mucosal biopsy specimens, with immunoglobulin deposition. The DSA C4d binding antibodies were also present. After intense immunosuppression and plasmapheresis, the graft and the biopsy histologic findings showed marked improvement (day 2). By day 7 posttransplantation, patient and graft status were stable. The patient has remained clinically stable for more than a year after transplantation.Conclusions: Pretransplant DSA in ITx can be a risk factor for immediate (hyperacute) but potentially reversible antibody-mediated rejection. Thus, pretransplantation DSA and cross-match results are critical components to be considered in patients awaiting or undergoing ITx.

Outcome of Exfoliative Rejection After Isolated Intestinal Transplantation in an Adult: Case Report

2010-01-01

Abstract: A 34-year-old-man with short-bowel syndrome received an isolated small bowel graft. On postoperative day (POD) 11, ileal biopsy specimen demonstrated mild to moderate rejection that did not respond to corticosteroid bolus therapy. On POD 14, endoscopy and histologic examination revealed exfoliative rejection that was not controlled after 14 days of therapy with thymoglobulin. On POD 95, the patient underwent surgery again because of intestinal obstruction. The graft was removed 6 months after transplantation because of continuous severe abdominal pain with weight loss. After enterectomy, the patient developed multiple-organ failure and died on POD day 8. This case underlines the severity of exfoliative rejection and suggests that early enterectomy be performed when the diagnosis is made, before deterioration of clinical status and development of infectious and nutritional complications.

Esophageal Varices in Chronic Intestinal Insufficiency in Absence of Portal Hypertension or Liver Cirrhosis: Case Report

2010-01-01

Abstract: We report the case of a 62-year-old man with short-bowel syndrome, referred for intestinal transplantation, who had esophageal varices (EV) due to superior vena cava (SVC) thrombosis. Pretransplantation work-up revealed protein S deficiency. Results of liver function tests were normal. Upper endoscopy showed grade II to III EV in the upper and middle segments of the esophagus. Computed tomography demonstrated thrombosis of the jugular, subclavian, and SVC veins and marked collateral vessels in the chest. Transient elastography yielded normal findings. A liver biopsy specimen showed a normal aspect of the liver, without fibrosis or liver cirrhosis. Presence of EV in a patient with chronic intestinal insufficiency may be related to collateral venous circulation associated with SVC thrombosis in the absence of portal hypertension. In this situation, an isolated intestinal graft is indicated.

World Day of Organ Donation and European Day of Organ Donation

2010-01-01

This years' conference of the ISODP was held in conjunction with the 5th World Day of Organ Donation and the 12th European Day of Organ Donation. Both events have been launched years ago by Professor Morel and were, for the first time, linked to the conference of the ISODP. It was the intention of the organizers to use celebrations to create public awareness to make people think about organ donation and most important to make their own decision in favor of organ donation. The event was advertised in Berlin and its surroundings. There were specifically designed posters and video screens in the public transportation system and everywhere as well as in the media. Luckily enough the organizers were able to utilize equipment which was installed in front of the Brandenburg Gate in Berlin for the German day of reunification October 3, 2009. The plan was to have a big show on the street with well-known musicians playing to attract people and to give them information about organ donation. Eighteen different patient organizations and official European national organizations distributed donor cards. The attendees could participate in discussions on stage with citizens and relatives of donors, waiting list patients and recipients. All this was supported by video statements from more than 30 important politicians from Germany and Europe, and from famous artists and actors such as Robert Redford on top of the list. The important part of the whole ceremony however was the statement of the patients being involved, telling their stories and giving an example what common solidarity means to everybody and specifically to organ donation. The combination of statements from citizens and celebrities who are in favor of organ donation created an atmosphere of allowing people to think about the subject and making their own decision. The attractions of the program were a number of music presentations from very well-known bands in Germany like Jeanette Biedermann, Karat, John Lees Barclay James Harvest. Alltogether they gave a five hour concert giving ample time for people to move around, go to the stands and booths of the patients associations and discuss with them about problems in organ donation. The format of this event turned out to be a very memorable one. Excellent media coverage was accomplished with more than 20 million people hearing about this event through TV, radio stations, or the press.

Preface

Günter Kirste — 2010-01-01

The 10th conference of the ISODP International Society Organ Donation and Procurement was held in conjunction with the 16th annual conference of the ETCO European Transplant Coordinators Organization in Berlin October 4th to 7th, 2009. More than 400 abstracts were received and evaluated by the Scientific Committee. The best ranked 96 abstracts were accepted for oral presentation in different sessions. The others were electronically displayed in a new format of electronic posters discussions only. These discussions created a lively atmosphere. It was the intention of the congress organizers to have a broad overview on all aspects of organ donation and procurement. The congress was held in conjunction with the World Day of Organ Donation and the European Day of Organ Donation—it was the biggest celebration about organ donation ever around the world bringing together more than 250.000 people in front of the Brandenburg Gate in Berlin.

The PIERDUB Project: International Project on Education and Research in Donation at University of Barcelona: Training University Students About Donation and Transplantation

M. Manyalich, D. Paredes, C. Ballesté, A. Menjívar — 2010-01-01

Abstract: Introduction: Donation and transplantation is an accepted therapeutic option when organ failure or tissue replacements are needed to save or improve the quality of life. However, in most medical schools there is no specific training for it, thus disregarding the key role of university students for the future success of the process.Objectives: Knowledge diffusion about the donation procedure to clarify doubts and stimulate positive attitudes toward donation. Training university students in the donation and transplantation process. Research about the previous donation knowledge and the impact in donation indexes.Methods: Three different phases have been designed: (1) Training the University of Barcelona Health Sciences School students; (2) Training the Health Sciences School students in other faculties of Catalonia, Spain, and International; and (3) research.Results: Since 2005, we have offered yearly an Optional Credits Course to medical students with duration of 45 hours, and two Donation days opened to health sciences students. Since 2007, promotional campaigns have been carried out in medicine and other health sciences faculties. Until now, 818 answered surveys have been collected to evaluate previous knowledge among university students.Conclusion: Training medical and other health sciences students in the donation process will improve quality of medical education and develop a trainer role for future professionals to help improve donation rates.

A National Program Toward Improving Renal Health: Advancing Organ Donation Awareness

2010-01-01

Abstract: Background: Despite the national advocacy campaign for kidney transplantation from deceased donors in the Philippines 96% of kidneys transplanted into 721 kidney transplants from 1999 to 2001 came from living donors. A national survey on the knowledge, attitudes and perceptions of Filipinos on organ donation in 2001 showed factors that disadvantaged deceased organ donation to be poor understanding of “brain death,” religion, and fear of the operation. These concerns were addressed and another survey was conducted in 2005.Objectives: To compare knowledge, attitudes, and perceptions of Filipinos on organ donation between 2001 and 2005, and compare the number of kidney transplants from deceased donors between 2001 until 2008.Methods: Two surveys in 15 regions of the Philippines were conducted using multistage sampling. Using a structured questionnaire there were 2000 respondents in 2001, and 2140 in 2005. Analysis was performed using chi-square analysis.Results: The majority of respondents knew about kidney donation. Between 2001 and 2005, there was increased awareness that transplants came from both living and deceased donors (37% to 41%) and a decline in those believing transplants came only from deceased donors (14% to 9%). Willingness to become a living (59% to 87%) or a deceased donor (35% to 49%) increased. The increase in transplantation from deceased donors from an average of 10 per year from 1999 to 2001 to 31 per year from 2006 to 2008.Conclusion: Increased awareness about kidney donation among Filipinos, improved consent to become an organ donor, and an increase in kidney transplantation from deceased donors occurred from 2001 to 2008.

Donor Compensation: An Ethical Imperative!

J.-O. Reichardt — 2010-01-01

Abstract: The number of living organ donors is increasing worldwide, but donor needs are widely neglected in support of anticommodification policies. This article argues that the warrant of donor autonomy during the decision process to donate is only one requirement of adequate donor care. Another is the donor's protection against the systematic and institutional exploitation of his altruistic dispositions. People with the disposition to support those, who are in desperate need, with a nonrenewable part of their own body, despite a small but unavoidable risk of death or health impairment, do not deserve to be additionally burdened with further disincentives, such as financial risks and uncompensated costs of donation. And although the borderline between a morally required disincentive removal and a more controversial net incentive to boost donation might be vague and open to discussion, to disadvantage living donors by design constitutes a serious barrier to the fairness of living organ donation—a barrier that should be removed.

Attitude of Health Care Professionals to Organ Donation: Two Surveys Among the Staff of a German University Hospital

2010-01-01

Abstract: The persistent shortage of organs for transplantation could be minimized by increasing the number of potential donors. The opinion of the staff of a university hospital toward organ donation is of special interest because they are directly involved in solid organ transplantation. In 2007, we conducted a first voluntary survey concerning organ donation among the staff of the university hospital of Essen. A short information campaign and further opinion poll among staff as well as visitors was performed in 2009 to compare professional and public attitudes toward organ donation. The first poll comprised 242 questionnaires showing 55% of the hospital staff carrying organ donor cards, particularly more women (60%) than men (46%). After this survey, an additional 19% of the hospital staff imagined they might carrying an organ donor card in the future. In the second survey, we analyzed 151 questionnaires, showing 66% of staff members carrying an organ donor card, an incidence significantly greater than among visitors (48%). The need for information regarding organ donation was greater among visitors (35%). However, 21% of the hospital staff still also need education concerning organ donation. More education and increased transparency of transplantation practice are necessary for hospital staff to act successfully as initiators. Hospital staff with positive attitudes toward organ donation may have a positive impact on the attitudes of the general public toward organ donation.

Organ Transplant Education: The Way to Form Altruistic Behaviors Among Secondary School Students Toward Organ Donation

I. Milaniak, P. Przybylowski, K. Wierzbicki, J. Sadowski — 2010-01-01

Abstract: Background: Organ shortage for transplantation is a crucial problem all over the world. Educational intervention may appeal to young people's altruism, increasing organ donation and decreasing the opposition.Aim: This study assessed the influence of an educational program, including organ donation and transplantation, to forming students' altruistic behaviors.Methods: A total 680 students of 25 secondary schools were asked about their attitudes, intentions, and knowledge about organ donation and transplantation from September 2008 to June 2009 during a 45-minute lesson.Results: In this study, altruistic attitudes were measured through questions about the expression of will to give organs away after death; to give one kidney to relatives; to use the bone marrow from a foreign person; and to sign a donor card. Attitudes were assessed by questions about conversations with relatives, an evaluation of the educational project. More than 1500 donor card were distributed and more than 90% of students wanted to sign them; 73.6% agreed to sign a donor card with the ID card. Before the project, only 8% of students had a signed donor card. Almost everybody is ready to agree to give their organs after death (80.6% male; 92.2% female), or to relatives (100% male; 90.38% female), or bone marrow (80% male; 55.7% female). The students talked to their family, informing them about their decision (36.9% male; 45.9% female).Conclusions: The proposed educational project successfully encouraged teenagers to make well-considered choices with regard to organ donation and created altruistic behaviors.

Health Content Analysis of Organ Donation and Transplantation News on Turkish Television Channels and in Turkish Print Media

M. Yavuz Çolak, D. Hekimoglu, K. Ersoy, F. Sozen, M. Haberal — 2010-01-01

Abstract: The media affects individuals' behaviors, especially by means of news and advertisements. In this study, we evaluated health content of organ donation and transplantation news in the printed media and on television programs for a 1-year period in Turkey. We examined 2449 news items in 230 newspapers and magazines; 1179 news programs on 45 television channels, all concerning organ donation and transplantation. The news obtained from the Media Pursuit Center were transferred to an electronic file to evaluate the format and content of the news. Nine variables were examined about the scope and the formal characteristics of the news: the publication name, its type, the province, the date, the headline, the title length, the presence of a photograph, or its kind, the news size, and the page number. In the content analysis of the news, we also examined 9 variables: the topic, the message of the headline, the property of the words in the title, the identification of photographs in the news, the age, gender of actors in the news, as well as donor or recipient. In a summary, print media and television channels, failed to show sufficient information about organ donation and transplantation. The percentage of news about organ donation and transplantation was small and mostly negative items in the media. On television channels, sufficient place was not given to organ donation and transplantation. The news in printed media and on television channels was not about motivated or altruistic behavior. The pattern of organ donation and transplantation news is important in terms of perception and comment by the public. Furthermore it directly affects the perception of the news by the reader.

The Role of an Interdisciplinary Transplant Team on Living Donation Kidney Transplantation Program

2010-01-01

Abstract: During the last decades, the disparity between the organ supply and the demand for kidney transplantation in Europe has led to consider living donors as a more acceptable option. In the last 7 years, we have established an interdisciplinary supporting transplant team to increase the rate of living donation. After 2001, the new interdisciplinary transplant team consisted of a transplant surgeon, a nephrologist, a pediatrician, a radiologist, a psychologist, a transplant coordinator, and a transplant nurse. We performed a prospective analysis to examine the effect of implementing this team on our living donation program. Demographic data, the annual number of procedures, the duration of waiting, and the cold ischemia time were evaluated among brain-dead and living donors. From January 2002 until December 2008, the number of patients who were annually on the waiting list increased 42% (from 377 to 536 patients). Consequently, the number of the total kidney transplants increased from 81 to 120 with an annual median of 98 cases. By implementing the interdisciplinary transplant team, a significant increase of living kidney donors was observed: from 18 to 42 cases; median = 27). In the last 7 years, a total number of 796 kidney transplants have been performed: 567 from brain-dead and 229 from living donors. In 2001, the waiting list times for recipients who received grafts from brain-dead versus living donors were 1356 versus 615 days respectively. Compared with 2008, the duration on the waiting list decreased significantly for patients receiving a living donor graft, whereas there was a slight increase for the patients in the brain-dead group: brain death versus living donors: 1407 versus 305 days. The interdisciplinary approach has also reduced the cold ischemia time for the living donor recipients: 3 hours and 42 minutes in 2001 versus 2 hours and 50 minutes in 2008. During the last years, by implementing an interdisciplinary transplant team, supporting living donor procedures has produce a gradual increase in the number of kidney transplants from living donors with a remarkable decrease in waiting and cold ischemia times, the latter presumably influencing graft quality.

The Rate of Organ and Tissue Donation After Brain Death: Causes of Donation Failure in a Romanian University City

I. Grigoraş, M. Blaj, G. Florin, O. Chelarescu, C. Craus, R. Neagu — 2010-01-01

Abstract: Aim: To evaluate the rate of organ donation after brain death in 2 tertiary care medical centers of a Romanian city, the reasons for donation exclusion (donors or organs), and identification of potential strategies for improvement.Material and Methods: The study retrospectively evaluated potential organ donors with brain death (BD) who were identified between January 2006 and June 2009 in an university city of Romania. The potential donors were considered patients with severe intracranial pathology and clinical signs of brain death who were reported to the regional transplant team. The BD declaration was completed according to the Law of Transplant Procurement and Management in Romania: clinical signs of brain stem death, apnea test, and flat EEG, criteria that must be fulfilled twice at a 6 hour interval. According to Romanian law, family consent is mandatory for organ harvesting.Results: The study included 35 potential donors, of whom 22 had a declaration of BD. Failure of potential donors to be declared BD was caused by positive viral serology (n = 7), improvement in clinical status (n = 2), sudden cardiac arrest (n = 2), and refusal of physician in charge (n = 2). Among the 22 with a BD declaration, organ harvesting was performed in only 12 cases due to family refusal (n = 10). In 4 cases the planned organ harvesting was aborted owing to unexpected intraoperative findings.Discussion: Factors that generate the low rate of organ procurement include local organizational particularities, a high rate of viral infections, poor education, (both of lay persons and of medical personnel), restrictive criteria for BD declaration and the mandatory need for family approval.Conclusion: The rate of donation in this university city of Romania is still low. Several strategies have been identified to improve the rate: better identification of potential donors, better management, and education of the public and of health care personnel.

Presumed Consent for Organ Donation: Is Romania Prepared for It?

I. Grigoras, C. Condac, C. Cartes, M. Blaj, G. Florin — 2010-01-01

Abstract: Introduction: In November 2007, a legislative initiative regarding the presumed consent for organ donation was proposed for parliamentary debate in Romania and was followed by public debate. The study aimed to asses public opinions expressed in the Romanian media.Materials and Methods: An Internet search was made. The pro and con reasons, the affiliation of parts involved in the debate and suggested future direction of action were identified.Results: The Internet search had 8572 results. The parts involved in the pro and con debate consisted of governmental structures, physicians, ethicists, politicians, media, religious authorities, nongovernmental associations, and lay persons. The main pros were the low rate of organ donation and the long waiting lists, enhancement of organ procurement, avoidance of wasting valuable organs, avoiding responsibility, and the stress imposed to the family in giving the donation consent, humanitarian purposes (saving lives), going along with the scientific progress, and less bureaucracy. The main cons were an unethical issue, violation of human rights, denial of brain death, unethical advantage of public ignorance, unethical use of underprivileged people, little results in terms of organ procurement, but huge negative effects on public opinion, public mistrust in transplant programs and impossibility of refusal identification due to particularities of the Romanian medical system.Conclusion: The con opinions prevailed. For the moment, Romania seems to be unprepared to accept presumed consent. A future change in public perception regarding organ transplantation may modify the terms of a public debate.

Functional Improvement Between Brain Death Declaration and Organ Harvesting

I. Grigoras, M. Blaj, O. Chelarescu, C. Craus, G. Florin — 2010-01-01

Abstract: Introduction: The quality of harvested organs is crucial for graft survival and for posttransplant evolution. This study sought to investigate the evolution of the functional status of brain death (BD) patients during the period between declaration and organ harvesting (BD duration).Materials and Methods: The study included all BD patients who underwent organ harvesting between January 2006 and June 2009. We compared the functional status regarding hemodynamics, respiration, kidney and liver function, coagulation, water, electrolytes, and acid–base balance evaluated at the moment of BD declaration (P1) and just before organ harvesting (P2). The results of the comparison were expressed as improvement, stable, or aggravation. We calculated mean values of the functional parameters in P1 and P2 and the statistical significance of the differences.Results: Twelve BD patients were included in the study. The time interval between P1 and P2 was 16.08 ± 8.54 hours (range, 6–32). The number of patients with vasopressor support was 9/12 at P1 and 0/12 at P2, oxygenation disturbances 1/12 in P1 and 0/12 in P2, renal dysfunction 9/12 in P1 and 2/12 in P2, liver dysfunction 7/12 in P1 and 1/12 in P2, coagulopathy 4/12 in P1 and 0/12 in P2, hypernatremia 8/12 in P1 and 3/12 in P2, and metabolic acidosis 9/12 in P1 and 1/12 in P2. The overall assessment showed improvement in all patients. The most statistically significant improvement was registered in the cardiovascular, respiratory, renal, liver, and acid–base status (P < .05).Conclusion: With early, aggressive, protocolized donor management, functional improvement may be achieved during BD duration.

The Donor Action Project: A Valuable Tool to Measure Quality and Efficacy of the Donation Process in Emilia-Romagna

L. Ridolfi, N. Alvaro, T. Campione, G. Zaza, M. Bonanno — 2010-01-01

Abstract: Introduction: The international project Donor Action (DA) started in Emilia-Romagna (ER) in July 1998, involving 24 main regional intensive care units (ICUs) of which 6 have neurosurgery units. Using a data-analysis computer system, we sought to measure the efficiency and quality of the donation process.Methods: Our study analyzed all data collected by the DA system from July 1998 to December 2008. In particular, we evaluated the following markers: patients with brain damage (BD)/total ICU deaths (Index I); brain death assessments/potential donors (PD, patients in the ICU for more than 6 hours; Index II); refusals/consent requests (Index III); effective donors/total encephalic deaths (PROC 1); and brain death assessments/total encephalic deaths (PROC 2). After collection, data were analyzed by the Regional Transplant Reference Center (CRT)-ER and sent to the National Transplant Centre (CNT) using Q-pido software for comparison with other Italian regions.Results: During the study period, despite a significant decrease in Index I, we observed a considerable increase in Index II, and, consequently, in donation efficacy. Additionally, we reported a slight increase in Index III. Finally, both PROC 1 and PROC 2 increased through the years, suggesting an improved efficacy of the donation/transplantation system.Conclusions: Based on our experience, the DA project to increase the level of attention of ICU medical staff about organ donation and to increase interactions between transplantation coordinators and CRT-ER seemed to ameliorate both procurement and transplantation activities.

Machine Perfusion Preservation for Kidney Grafts With a High Creatinine From Uncontrolled Donation After Cardiac Death

2010-01-01

Abstract: Background: This study evaluated the usefulness of machine perfusion preservation parameters as selection criteria for donation after cardiac arrest (DCD) with high creatinine level. The aim of this study is to evaluate to whether DCD donor >50 years old and with high creatinine are acceptable.Methods: We examined 17 kidneys from uncontrolled DCD who showed creatinine levels >3.0 mg/dL before procurement. The study included the following two groups: group 1 (n = 9), donor age <50 years old versus group 2 (n = 8), donor age >50 years old.Results: There were no significant differences in donors or preservation conditions among the 2 groups, including age, terminal creatinine, warm ischemic time, cold perfusion time, and total ischemic time. A greater resistance of 47.9 mmHg/mL per min/g was observed among group 2, compared with 42.5 mmHg/mL per min/g in group 1. A shorter ATN period (8.2 days) was noted in group 1, compared with 21.2 days for group 2. The flow rate (mL/g/min) was not significantly different between the two groups. The best-Cr level was 1.22 mg/dL in group 1 and 1.94 mg/dL in group 2.Conclusion: Machine perfusion flow was a reliable indicator of graft viability in uncontrolled DCD, particularly kidneys with high creatinine level. Even older donors were acceptable if the machine perfusion preservation parameters such as flow rate and pressure were acceptable; however, they may show severe delayed graft function.

New Insights Into Fatty Liver Preservation Using Institute Georges Lopez Preservation Solution

2010-01-01

Abstract: Institute Georges Lopez preservation solution (IGL-1) has been demonstrated to be useful for fatty liver preservation. The mechanisms responsible for this effective graft protection against ischemia-reperfusion injury are pivotal actions on generation of nitric oxide a diffusible molecule with vasodilator properties, that facilitates the up-regulation of other well-known cytoprotective genes, such as hypoxia-inducible factor-1 alpha (HIF-1α) and heme-oxygenase 1 (HO-1). During normoxic reperfusion, the presence of nitric oxide permits HIF-1α accumulation to inhibit prolyl-hydoxylases, thus promoting an additional overexpression of the HO-1 in steatotic and nonsteatotic graft livers preserved in IGL-1.

A Fast and Safe Living Donor “Finger-Assisted” Nephrectomy Technique: Results of 359 Cases

2010-01-01

Abstract: Objective: To determine operative parameters and complications, using a modified approach to mini-incision living donor nephrectomy.Methods: Three hundred fifty-nine consecutive living donor procedures were performed between October 2000 and November 2008 using the finger-assisted, mini-incision living donor nephrectomy. Patient demographics, intraoperative parameters, and postoperative complications were prospectively recorded, including operative time, blood loss, incision length, warm ischemia time, and intraoperative adverse events.Results: Mean donor age was 44.2 ± 12.3 years (range, 21–75 years), with an average body mass index of 28.2 ± 5.3 kg/m2 (range, 17.1–44.9 kg/m2). Right-sided donor nephrectomies were performed on 23 patients (6%), and 41 donors (11%) were found to have multiple renal arteries. Median incision length was 6.8 cm (range, 3.5–15 cm). Average operative time was 117 minutes (range, 50–265 minutes), with a median blood loss of 109 mL (range, 20–500 mL) and an average warm ischemia time of 4.5 minutes (range, 1.5–10 minutes). Four patients (1%) required perioperative blood transfusions. There were no other intraoperative complications, no patients required reexploration, and there were no donor deaths. Thirteen patients (4%) developed minor postoperative complications, including two incisional herniae, but no patients developed chronic wound pain, over a median follow-up period of 19 months (range, 2–97 months).Conclusion: This prospective series demonstrated that a modified approach to open mini-incision nephrectomy can result in a smaller incision length while maintaining patient safety, with few postoperative complications.

Deceased Donor Organ Transplantation With Expanded Criteria Donors: A Single-Center Experience From India

2010-01-01

Abstract: Introduction: Deceased donor organ transplantation (DDOT) accounts for <4% of renal transplants in India. Many volunteers come forth for organ donation with increasing awareness; unfortunately, the majority are marginal donors, but their rejection would hamper the DDOT program. Judicious use of marginal organs is a challenge for developing countries.Patients and Methods: We performed 29 renal transplants from 21 expanded criteria donors (ECD) out of 115 DDOT between January 2006 to April 2009—10 dual (DKT) and 19 single (SKT). Fourteen donors had hypertension, a cerebrovascular accident as the cause of death, 9 had both, and 4 had diabetes. Mean donor age was 70.3 ± 8.9 years. Decisions on the procedure were based upon frozen section biopsy in 13 of 21 donors. Mean DKT donor age was 76 ± 9.7 years versu 64 ± 5.7 years of SKT donors. The native kidney diseases were chronic glomerulonephritis (n = 14), diabetic nephropathy (n = 7), tubulointerstitial nephritis (n = 4) and polycystic kidney disease, focal segmental glomerulosclerosis, lupus nephritis and patchy cortical necrosis, (n = 1 each). Mean recipient age of DKT versus SKT was 43.5 versus 42.3 years. All recipients received rabbit anti-thymocyte globulin, followed by steroid, mycophenolate mofetil/calcinueurin inhibitor.Results: Over a mean follow-up of 341 days, the mean serum creatinine (SCr) of 25/29 patients was 1.60 mg/dL (range, 1.0–2.6). The mean SCr of SKT patients was 1.59 ± 0.63 mg/dL and of DKT, 1.62 ± 0.48 mg/dL. Ten patients had delayed graft function and 11 had biopsy proven acute tubular necrosis. Seven (24%) patients had rejection (grade 3 Banff update '05, type IA; 4, type 2A); 6 responded to antirejection; 1 graft was lost at 7 months due to chronic rejection. Three (10.3%) patients were lost, 1 each due to AMI, sepsis, and CMV disease.Conclusion: In the circumstances of organ shortage, DDOT with expanded criteria donor is a feasible option.

Liver Transplantation Utilizing Old Donor Organs: A German Single-Center Experience

F. Rauchfuss, R. Voigt, Y. Dittmar, M. Heise, U. Settmacher — 2010-01-01

Abstract: Introduction: Due to the current profound lack of suitable donor organs, transplant centers are increasingly forced to accept so-called marginal organs. One criterion for marginal donors is the donor age >65 years. We have presented herein the impact of higher donor age on graft and patient survival.Patients and Methods: Since 2004, 230 liver transplantations have been performed at our center, including 54 donor organs (23.5%) from individuals >65 years of age. We performed a retrospective analysis of recipient and graft survivals.Results: The overall 1-year mortality was 22.2% (12/54) among recipients of organs from older donors versus 19.5% among recipients whose donors were <65 years. When donor organs were grouped according to age, the 1-year mortality in patients receiving organs from donors aged 65–69 years was 30% (6/20); 70–74 years, 29.4% (5/17); and donors >75 years, 5.9% (1/17). There was no significant correlation between mortality rate and the number of additional criteria of a marginal donor organ.Discussion: The current lack of donor organs forces transplant centers to accept organs from older individuals; increasingly older patients are being recruited for the donor pool. Our results showed that older organs may be transplanted with acceptable outcomes. This observation was consistent with data from the current literature. It should be emphasized, however, that caution is advised when considering the acceptance of older organs for patients with hepatitis C–related cirrhosis.

Preprocurement Pancreas Allocation Suitability Score Does Not Correlate With Long-Term Pancreas Graft Survival

P. Schenker, O. Vonend, N. Ertas, A. Wunsch, R. Viebahn — 2010-01-01

Abstract: Backround: Within recent years, more marginal donors have been offered to Eurotransplant. To help identify suitable pancreas donors, the Eurotransplant Pancreas Advisory Committee introduced a donor score system (P-PASS). Little is known about the influence of P-PASS on long-term pancreas graft survival.Methods: From June 1994 to September 2009, we performed 405 pancreas transplantations. In a retrospective study we analyzed P-PASS in 318 cases. Pancreas grafts from donors with P-PASS < 17 (n = 146) analyzed for graft and patient survival as well as for surgical complications were compared with donors of a PASS ≥ 17 (n = 172). The mean follow-up was 7.2 ± 4.3 years.Results: Recipient characteristics were comparable in both groups. Mean P-PASS was 16.7 ± 2.7 for both groups: 14.3 ± 1.5 for P-PASS < 17 and 18.8 ± 1.6 for P-PASS ≥ 17. Pancreas graft survival rates for 1, 5, and 10 years were 85%, 77%, and 73% among P-PASS < 17 and 81%, 73%, and 64% among P-PASS ≥ 17 groups (P = .12). There were 12 (8.2%) cases of venous thrombosis in the <17 group and 22 (12.7%) in the ≥17 group (P < .05). The relaparotomy rate was significant higher (38.7% vs 28.7%) and duration of hospital treatment longer (40.2 vs 32 days) in the P-PASS ≥ 17 group (P < .05). There was no significant difference in patient or kidney graft survival between groups.Conclusions: The data demonstrated that utilization of pancreas grafts from donors with a P-PASS ≥ 17 resulted in good overall outcomes and could expand the organ donor pool. There was no correlation between P-PASS and long-term patient or graft outcome. Complications requiring relaparotomy were more frequent among patients after transplantation from donors with higher P-PASS.

European Homograft Bank: Twenty Years of Cardiovascular Tissue Banking and Collaboration With Transplant Coordination in Europe

2010-01-01

Abstract: Established in 1989 in Brussels as an international nonprofit association, the European Homograft Bank (EHB) has been collaborating closely with the transplant coordination of the different centers in Belgium and other European countries. Donor selection is made after discussion of exclusion criteria with the transplant coordinator of the procurement center. EHB collaborates with 15 Belgian, 11 German, 10 French, 10 Swiss, 3 Italian, 3 Dutch, and some other procurement and/or implantation centers. Donor ages range from newborn to 65 years. Tissue preparation, morphologic evaluation, and functional testing are performed under Class A laminar flow. After decontamination in a cocktail of 3 antibiotics (lincomycin, vancomycin, and polymixin B) during 20–48 hours, the tissues cryopreserved with liquid nitrogen to −100°C are stored in vapors of liquid nitrogen below −150°C for a maximum of 5 years. Systematic virologic examination of donor blood is performed for HIV, HTLV, hepatitis B/C, and syphilis, as well as for enteroviruses, Q fever, malaria, and West Nile virus by indication. Bacteriologic examination for anaerobic and aerobic contamination is performed at the different steps of processing. Histologic examination for malignant disease and infection is performed systematically. Indications for implantation are discussed with the requesting surgeon. Transport to the implantation center is carried out safely in a dry shipper at −150°C or in dry ice at −76°C. The EHB received 4,511 hearts and 1,169 batches of arteries from January 1989 to December 2008. The 5,133 heart valves (1,974 aortic, 3,106 pulmonary, and 53 mitral) and 2,066 arterial segments have been prepared and stored; 4,600 cryopreserved valvular (2,717 pulmonary, 1,835 aortic, and 48 mitral) and 1,937 arterial allografts have been distributed for implantation in various European Cardiovascular Centers. EHB is not always able to meet the increased demand for heart valves and arterial allografts.Collaboration between the EHB and the Transplant Coordination is satisfactory. Donor selection criteria are discussed with the transplant coordinator; whereas, implantation indication, with the implanting surgeon. Because the EHB is not always able to meet demands for the cryopreserved valves and arterial segments, there is a need to increase number of procurements. Cardiovascular surgeons need to play more active roles in the resolution of this problem.

Tissue Procurement System in Japan: The Role of a Tissue Bank in Medical Center for Translational Research, Osaka University Hospital

H. Ohkawara, N. Fukushima, T. Kitagawa, T. Ito, Y. Masutani, Y. Sawa — 2010-01-01

Abstract: Although organ procurement has been regulated by The Organ Transplantation Law (brain-dead donors since 1997, donors after cardiac death since 1979), there has been no law or governmental procurement network (except for cornea) in Japan. Since the late 1980s, some university hospitals have developed original banks. Finally, in 2001 guidelines for tissue procurement were established by The Japanese Society of Tissue Transplantation and Japan Tissue Transplant Network (JTTN) to coordinate tissue harvesting. Five tissue banks were joined to the tissue transplant network (skin in one, heart valves in two, and bone in two). As the number of tissue banks is small, each bank cooperates on procurement, but cannot cover the entire country. With regard to skin transplantation, only one skin bank—The Japan Skin Bank Network (JSBN), which is located in Tokyo—has organized skin procurement. Therefore, it has been difficult to procure skin in areas distant from Tokyo, especially around Osaka. In order to improve such a situation, a tissue bank collaborating with the JSBN was established at The Medical Center for Translational Research (MTR), Osaka University Hospital in April 2008. The bank has played a role in skin procurement center in western Japan and supported procurement and preservation at the time of the skin procurement. Between April 2008 and September 2009, the bank participated in eight tissue procurements in the western area. In the future, the bank is planning to procure and preserve pancreatic islets and bones. Moreover, there is a plan to set up an induced pluripotent stem cells center and stem cell bank in MTR. This tissue bank may play a role to increase tissue procurement in Japan, especially in the western area.

Protective Effects of N-Acetylcysteine on the Liver of Brain-Dead Ba-Ma Mini Pig

J. Li, S. Zhang, Y. Wu, W. Guo, Y. Zhang, W. Zhai — 2010-01-01

Abstract: Objective: To investigate liver injury after brain-death in BA-Ma mini pigs and the protective effects of N-acetylcysteine (NAC) on hepatic function and on nuclear factor (NF)-κB mRNA and protein expression.Methods: Fifteen Ba-Ma mini pigs were equally divided into three groups at random: brain-dead group (group B), NAC-pretreated group (group N), and control group (group C). A brain-death model was established by increasing intracranial pressure in a modified, slow, and intermittent way. At 6, 12, and 24 hours after the initial brain death, we determined the levels of serum aspartate transferase (AST), alanine transferase (ALT), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. At the same times, hepatic tissue samples were obtained to assess morphological changes in hepatic tissues and the expression of NF-κB mRNA and protein was detected by reverse transcriptase polymerase chain reaction and immunohistochemistry, respectively.Results: The levels of AST and ALT in groups B and N began to increase at 12 hours after brain death; the levels among group N were lower than those in group B (P < .05). The levels of serum IL-1β, IL-6, and TNF-α in group B and group N began to increase gradually at 6 hours after brain death; those of group B were all significantly greater than those among group N at each time (P < .05). The mRNA and protein levels of NF-κB among groups B and N began to increase at 6 hours after brain death; however, those of group B were all significantly higher than those of group N (P < .05). Light and electron microscopy showed only mild edema of liver cells in group N. At 12 hours after brain death, mitochondrial swelling and edema in liver cells were observed among group B, with more severe morphological lesions in this group than group N.Conclusions: NAC inhibited the degree of NF-κB mRNA transcription and its protein translation, decreasing the release of inflammatory factors, and thus alleviating hepatic injury during brain death.

Terlipressin as Rescue Therapy in Catecholamine-Resistant Hypotension in Solid Organ Donors: A Case Report

P. Vecchiarelli, F. Ricci, T. Riccini — 2010-01-01

Abstract: Objective: The objective of this study was to report the effects of Terlipressin treatment in 2 potential organ donors with intractable, catecholamine-resistant hypotension.Design and Setting: This study was based on case reports in the intensive care unit of a general hospital.Patients: Patients included 2 adult patients with cerebral death and catecholamine-resistant hypotension.Interventions: A low dose of Terlipressin (3.5 μg/kg) by intravenous bolus was added to the standard treatment.Measurement and Results: In both cases, Terlipressin induced a rapid improvement in arterial pressure with a consequent increase in urine output and the appearance of diabetes insipidus. In 1 patient it allowed for the withdrawal of norepinephrine infusion. No related adverse effects were detected in either patient. Organ removal was not possible in the second case due to lack of family consent.Conclusions: Terlipressin might be considered as a rescue therapy for potential organ donors with intractable, catecholamine-resistant hypotension. In spite of the positive results obtained here and by other authors in the treatment of septic shock, its judicious use is recommended, and an optimal administration schedule must still be elucidated.

Review of the Uruguayan Kidney Allocation System: The Solution to a Complex Problem, Preliminary Data

M. Bengochea, I. Álvarez, R. Toledo, E. Carretto, D. Forteza — 2010-01-01

Abstract: The National Kidney Transplant Program with cadaveric donors is based on centralized and unique waitlist, serum bank, and allocation criteria, approved by Instituto Nacional de Donación y Trasplante (INDT) in agreement with clinical teams. The median donor rates over last 3 years is 20 per million population and the median number of waitlist candidates is 450. The increased number of waiting list patients and the rapid aging of our populations demanded strategies for donor acceptance, candidate assignment, and analysis of more efficient and equitable allocation models.The objectives of the new national allocation system were to improve posttransplant patient and graft survivals, allow equal access to transplantation, and reduce waitlist times. The objective of this study was to analyze variables in our current allocation system and to create a mathematical/simulation model to evaluate a new allocation system. We compared candidates and transplanted patients for gender, age, ABO blood group, human leukocyte agents (HLA), percentage of reactive antibodies (PRA), and waiting list and dialysis times. Only 2 factors showed differences: highly sensitized and patients >65 years old (Bernoulli test).An agreement between INDT and Engineering Faculty yielded a major field of study. During 2008 the data analysis and model building began. The waiting list data of the last decade of donors and transplants were processed to develop a virtual model. We used inputs of candidates and donors, with outputs and structure of the simulation system to evaluate the proposed changes. Currently, the INDT and the Mathematics and Statistics Institute are working to develop a simulation model, that is able to analyze our new national allocation system.

Spanish and Latin American Nursing Personnel and Deceased Organ Donation: A Study of Attitude

2010-01-01

Abstract: Objective: To analyze the attitude of nursing personnel about organ donation and transplantation in hospitals in Spain and Latin America, and factors that affect this attitude.Methods: Data were selected from 12 hospitals and 32 primary care centers participating in an international study (Proyecto Donante, Murcia) in 4 countries including Spain (n = 650), Mexico (n = 428), Cuba (n = 89), and Costa Rica (n = 27). The sample was random and stratified by type of service among nursing personnel (n = 1194). Attitude was evaluated using a psychosocial questionnaire.Results: Of nursing personnel surveyed, 77% (n = 922) were in favor of organ donation. No differences were found according to whether they were directly involved in transplantation-related services (P < .05). Attitude in favor of organ donation varied between countries: 92% in Cuba, 85% in Costa Rica, 80% in Mexico, and 73% in Spain (P < .001) This attitude was also related to donation of a family member's organs (P < .001), having discussed organ donation and transplantation within the family (P < .001), the concept of brain death (P < .001), fear of body mutilation (P < .001), and manipulation of the body after death (P = .001).Conclusion: Attitude toward deceased organ donation among nurses varies between countries. There is a discrepancy between those in favor vs actual donation rates in countries and work centers. These fears may become worse when donation is seen as common in daily clinical practice.

Level of Acceptance of a Clinical Solid Organ Xenotransplantation Program Among Personnel in Organ Transplant-Related Services in Spanish, Mexican, and Cuban Hospital Centers

2010-01-01

Abstract: Introduction: Xenotransplantation is far from becoming a clinical reality. However, in vital organs it could be used as a bridge until a human organ becomes available, in an emergency situation. We analyzed the attitude toward xenotransplantation among personnel in transplant-related services in several hospitals in Spain and Latin America.Methods: A random sample stratified by type of service and job category (n = 738), in transplant-related services (procurement units, transplant units, and transplant patient follow-up units) was examined in eight hospital centers from three different countries: Spain (n = 349), Mexico (n = 269), and Cuba (n = 120). A self-administered validated questionnaire was completed anonymously.Results: Based on the assumption that all the results of xenotransplantation were similar to those achieved with human donors, most respondents [66% (n = 484)] would be in favor. The employees from Cuban centers had the most favorable attitudes (72% in favor), followed by the Spanish (64%) and the Mexicans (61%; P = .013). However, the differences were mainly determined by job category: Physicians showed the most favorable attitudes and auxiliary staff the least (67% vs 40%; P = .010). Attitudes were significantly related to beliefs about different types of human donation [deceased (P < .001) and living (P < .001)], the possibility of needing a transplant for oneself (P < .001), and a favorable attitude toward donating the organs of a deceased family member (P = .004).Conclusions: Currently, a third of health care employees working in transplant-related services are not in favor of xenotransplantation. More information should be provided about the subject, especially in centers with preclinical xenotransplantation programs.

Attitudes Toward Living Kidney Donation in Transplant Hospitals: A Spanish, Mexican, and Cuban Multicenter Study

2010-01-01

Abstract: Introduction: Living donor kidney (LKD) transplantation provides better results than deceased donor donation, involving minimum risk for the donor. However, LKD donation rates are low in most countries. We analyzed attitudes toward LKD in transplant hospitals in Spain, Mexico, and Cuba.Materials and methods: Data were obtained from five transplant hospitals through the International Collaborative Program “Proyecto Donante Vivo, Murcia” in three countries: Spain (n = 1168), Mexico (n = 903), and Cuba (n = 202). The random sample (2273 employees) was stratified according to job category. The instrument used to evaluate attitude was a validated questionnaire. Statistical analysis included Student t test, the χ2 test, and multivariate analysis.Results: Eighty eight percent (n = 2002) of Spanish, Mexican, and Cuban transplant hospital personnel were in favor of related LKD and 24% nonrelated LKD (n = 555). Attitudes were more favorable among centers in Cuba 97% (n = 195), followed by Mexico 88% (n = 793) and by Spain 87% (n = 1014; P < .001). According to job category, 91% (n = 617) of physicians were in favor, 88% (n = 543) of nurses, 85% (n = 198) of health care assistants, and 85% (n = 198) of auxiliary personnel. Attitudes were related to variables of: attitude toward deceased donation (P < .001), discussion about organ donation and transplantation (P < .001), concern about body mutilation after donation (P = .001), a possible need for a transplant in the future (P < .001), and attitude toward living liver donation (P < .001).Conclusions: Attitudes toward LKD in Hispanic/Latin Transplant Hospitals were favorable and could encourage an increase in LKD in the coming years assuming suitable sociopolitical and economic condition, as well as support from nephrologists.

Attitudes of Spanish and Mexican Resident Physicians Faced With Solid Organ Donation and Transplantation

2010-01-01

Abstract: Introduction: The attitudes of specialist physicians toward organ donation and transplantation are of great interest because promotion of this activity depends on them. Our objective was to analyze the attitudes of residents in health centers in Spain (MIR) and in Mexico (ENARM).Materials and methods: A random stratified sample was obtained in six teaching hospitals: two in Spain (n = 246) and four in Mexico (n = 139) as part of the International Collaborative Program “Proyecto Donante, Murcia.” The sample consisting of 385 trainee physicians completed a psychosocial questionnaire as the instrument to test their opinions.Results: Most residents (93%; n = 359), were in favor of deceased organ donation with 90% (n = 348) in favor of living kidney donation and 87% (n = 335) in favor of liver donation. Attitudes toward donation were similar among Spanish and Mexican residents regarding deceased donation (93% vs 94%; P > .05), living kidney donation (88% vs 94%; P > .05), and living liver donation (86% vs 89%; P > .05). None of the attitudes toward donation was associated with the classic psychosocial factors related to attitudes toward donation or job factors. Discussion within the family was associated with more positive attitudes toward deceased donation (P < .001), living donation of the kidney (P = .01), and of the liver (P = .019).Conclusion: Attitudes toward various types of donation were favorable among both Spanish and Mexican trainee physicians, so that they could potentially act as a group to promote this activity, raising hopes for increased donation rates in the future.

Organ Donation and Transplantation Training for Future Professional Nurses as a Health and Social Awareness Policy

2010-01-01

Abstract: Introduction: Training and information for university nursing students about the organ donation and transplantation process is necessary because it will influence their attitudes toward the subject. We analyzed attitudes toward organ donation among nursing students in a donation and transplantation training course and any changes in opinions as a result of the course.Materials and methods: We questioned 48 students in the third year of nursing (University of Murcia, Spain) who were attending a 32-hour training course about donation and transplantation. We used a descriptive concurrent study, through the completion of a validated opinion survey with 27 items before and after the training course.Results: Attitudes toward donation were favorable in 87% of respondents increasing to 94% after course completion. Before starting the course, 87% believed that there were not enough transplantable organs available to cover needs compared to 96% after the course. Before the course, 46% stated that they did not have complete information about the subject. Taking part in the course has encouraged family discussion about the subject (85% to 90%) and improved knowledge about family opinions (64% to 83%; P = .031). Attitudes toward living donation did not change after the course. However, there was an improvement in knowledge of the Spanish organ distribution system.Conclusions: Attitudes toward organ donation among third-year nursing students were favorable, and increased after undergoing a course about donation and transplantation. The most important part of the course was the increase in theoretical knowledge about the matter as well as the health education.

Effects of Immunosuppressive Drugs on Rat Renal Ischemia Reperfusion Injury

C. Parra, P. Salas, J. Dominguez — 2010-01-01

Abstract: Introduction: Recent evidence has demonstrated that the immune response and, more specifically, lymphocytes (T and B) and dendritic cells participate as mediators of renal ischemia reperfusion injury (IRI). The aim of this study was, therefore, to evaluate the effect of various immunosuppressive drugs with known activity to prevent IRI among rats undergoing a scheme that is potentially applicable in the clinic.Methods: Male Sprague-Dawley rats (200–300 g) underwent 60 minutes of ischemia by renal artery clamping and contralateral nephrectomy. The experimental groups (n = 6–7) were as follows: I, Sham; II, Control; III, Rapamycin (R; 1 mg/kg); IV, Methylprednisolone (M; 15 mg/kg); V, Vitamin D3 (VD3; 2 μg/kg); VI, VD3 (1 μg/kg); and VII, M (15 mg/kg) + R (1 mg/kg). Each drug was administered in 2 doses at 6 hours and 1 hour before surgery. Creatinine (Cr) was determined on days 0.1, 2, 3, 5, and 7, and Cr clearance was determined on days 3 and 7. At 7 days nephrectomy was performed to obtain samples for histology to evaluate the degree of acute tubular necrosis.Results: Mortality from renal insufficiency was between 0 and 33%, except in group V (66%; 4/6; P = .01). Kidney function was similar to controls in all groups except for creatinine at 7 days between group VI (VD3) and control (1.05 vs 0.65; P < .05) but no difference in Cr clearance. Histologically moderate to severe renal damage was greater in groups V and VI (VD3) than controls (P = .04).Conclusion: We observed that none of the drugs conferred protection against IRI in a time setting relevant to kidney transplantation. Controversy exists regarding R, because some prior studies have shown a deleterious effect on IRI injury, although we did not observe any deleterious effect.

Evaluation of the Stages Involved in Cold Ischemia Time in Renal Transplants in Chile

2010-01-01

Abstract: Introduction: Cold ischemia time (CIT) is one of the factors that determine the evolution of a renal transplant; taking measures to reduce this time requires knowledge of its stages. The objective of this study was to evaluate the times in the stages that determine CIT in renal transplants.Methods: We analyzed 108 donors and 201 kidney transplantations performed in Chile in 2008, establishing the CIT for the kidney transplanted by the center that extracted the kidneys (local kidney) and for the kidney transplanted in another center (shared kidney).Results: Average CIT was 18.8 hours: namely, 16.9 hours for local and 20.2 hours for shared kidneys (P = .0001484). CIT for cases in which samples were sent to histocompatibility laboratory prior to nephrectomy was 7.3 hours less than for those sent postnephrectomy. The mean time between the allocation of the kidney and the transplant was 7.3 hours; 5.6 hours for local kidneys and 8.4 hours for shared kidneys (P = .000007124).Conclusion: We identified the stages at which intervention is possible to reduce the CIT, mainly for shared kidneys. All involved parties should make an effort to reduce this time.

Evaluation of Late Immunologic Parameters Among Renal Transplant Recipients Induced With Campath-1H

2010-01-01

Abstract: Organ transplantation success depends principally on avoiding rejection, a purpose almost accomplished with immunosuppressant therapy. Nevertheless, drug side effects have promoted the search for other mechanisms to restrain alloresponses. T-regulatory cells (Treg) might exert that function. Campath 1H (C1H) induces Treg proliferation in the period subsequent to T-cell depletion following C1H administration. In the present study, the status of Treg and de novo HLA antibody production was determined posttransplantation when T-cell repopulation had been completed. In 14 patients, the following parameters were analyzed: renal function, rejection, Treg, panel-reactive antibody (PRA), and HLA antibodies. Patient and graft survivals were 100%. At the moment of Treg determination (20 months following transplant) the mean tacrolimus level was 8.4 ng/mL. One patient experienced an antibody-mediated rejection at 15 months after transplantation while having 3.2% Treg, with excellent treatment responses. Mean leukocyte and lymphocyte counts were 5752 and 1183 cells/mm3; the mean peripheral blood percentage of Treg of 7.1% ± 5.9% was not different from that observed in subjects without induction (mean 5.5% ± 2.5%). Three patients (21%) showed Treg greater than 8.0%. In seven patients, we compared Treg at 4 and 20 months posttransplant, observing a decline from a mean of 19.9% to 5.9% (P = .05). In seven recipients, posttransplant PRA was determined; five of them became “de novo” sensitized, three with a mean class I PRA of 16% and two with a mean class II PRA of 37%. In conclusion, patient and graft survivals were excellent, mean Treg percentage was not elevated with results lower than in the early posttransplant period. Rejection incidence was negligible. Late “de novo” sensitization occurred in 70% showing that B cell–mediated alloresponses were only partially controlled among recipients induced with C1H even when associated with sustained anticalcineurin treatment.

Pharmacogenetics of Immunosuppressant Polymorphism of CYP3A5 in Renal Transplant Recipients

J. Larriba, N. Imperiali, R. Groppa, C. Giordani, S. Algranatti, M.A. Redal — 2010-01-01

Abstract: The tacrolimus is metabolized primarily by CYP3A5, a member of the single nucleotide polymorphism family. It shows cytochrome P450 (SNP) in intron 3, which consists of a change of base, G for A, producing a stop codon. The result is a nonfunctional protein (allele *3). Allele *1 is the wild type. The patients that show the allelic variant *3 in homozygosis (G/G) are slow metabolizers of the immunosuppressant, increasing its concentration in blood. In contrast, heterozygote A/G alleles *1/*3 are intermediate metabolizers, whereas those of allele *1 in homozygosis (A/A) are normal metabolizers. The aim of this study was to determine CYP 3A5 polymorphism among adult renal transplant recipients and the general Argentinean population. We analyzed 21 recipients and 36 healthy controls. All subjects gave written informed consent approved by the local committee. To determine the polymorphism, we extracted DNA from peripheral blood and used polymerase chain reaction (PCR) to amplify intron 3 of the CYP 3A5. The presence of variant was confirmed by direct sequencing. Among the controls the CYP3A5 genotype *3/*3 (G/G) was detected in 32 individuals, 4 showed *1/*3 (A/G), and none had *1/*1 (A/A); among the recipients, the results were as follows: 18, 2, and 1, respectively. The frequencies of polymorphism in both groups were similar, although they differred from those published for other populations. These results are the basis for the development of a pharmacogenomic program applied to organ transplantation. The genetic polymorphisms can determine responses to drugs. The molecular diagnosis must be transferred to clinical practice so as to guide selection of medicine and drug doses to be optimal for each individual.

Prediction of Renal Function After Living Donor Kidney Transplantation

2010-01-01

Abstract: There is no reliable method to predict the ideal expected function after a kidney transplantation. Herein we have described our experience in the living donor kidney transplant setting, comparing donor and recipient renal function (body surface area adjusted) before the LDKT, and during six months after this procedure. We determined the expected relation between donor and recipient renal function as well as its evolution over time.

Parameters of Doppler Ultrasound at Five Days Posttransplantation as Predictors of Histology and Renal Function at One Year

2010-01-01

Abstract: Introduction: In our center, a Doppler ultrasound (DU) is performed at 5 days after transplantation. The normal upper limit of flow velocity (FV) in the renal artery is 200–250 cm/s. The resistance index (RI) is considered elevated when >0.8. Elevation of the RI can be shown in all the forms of graft dysfunction.Objective: The objective of this study was to evaluate the capacity of the DU to predict the prognosis of graft function and histological damage at 1 year.Methods: We examined a retrospective cohort of patients undergoing renal transplantation between January 2004 and May 2007. The renal function was evaluated with serum creatinine measurements and glomerular filtration rate (GFR) estimates by the quadratic Modification of Diet in Renal Disease study equation. The biopsy specimen was evaluated according to the Banff 1997 classification.Results: The overall average age was 35 years, and 58% of the subjects were men. Eight cases (25.8%) showed abnormal DU. The Delta among those with normal DU was −0.94 versus 0.27 ± 0.39 with abnormal DU (P < .005). There was no significance as far as the biopsy at 1 year.Conclusions: Renal DU allows physicians to suspect complications at the first posttransplantation year. It shows a tendency to elevated blood pressure, as well as increased deterioration of renal function over the first year.

Evaluation of HLA Matchmaker Compatibility as Predictor of Graft Survival and Presence of Anti-HLA Antibodies

2010-01-01

Abstract: Background: HLA Matchmaker is a computer algorithm developed to evaluate donor/receptor compatibility comparing sequences of polymorphic aminoacids (eplets) present in human leukocyte antigen (HLA) molecules. The aim of this study was to evaluate the predictive value of HLA Matchmaker for patient and graft survival, graft survival free of rejection, and the presence of anti HLA antibodies.Methods: Using this program, 62 of 173 kidney transplant patients, were retrospectively analyzed. HLA-I loci eplet mismatch value (EMM) was determined and correlated with graft survival, graft survival free of rejection, and the presence of anti HLA-I antibodies. EMM was compared with the traditional HLA antigen mismatch value (MM) in terms of the presence of anti HLA-I antibodies.Results: Graft survival and graft survival free of rejection showed no statistical differences (P-value .975 and .365, respectively) while comparing patients with less or more than 10 HLA-I EMM. Patients with ≥6 HLA-B EMM had an odds ratio (OR) of 5.6 (95% confidence interval [CI], 0.47–66.45) of presenting anti HLA-I antibodies, with a sensitivity of 80% and specificity of 58.3%. For ≥2 HLA-B MM, the OR was 2.58 (95% CI, 0.46–14.5), with a sensitivity of 40% and specificity of 75%.Conclusion: Even though in our study population compatibility by HLA Matchmaker did not correlate with graft survival or rejection-free graft survival, it showed a better sensitivity than traditional HLA antigen matching for the presence of anti HLA-I antibodies. HLA Matchmaker is a promising tool in predicting the appearance of anti-HLA antibodies.

Everolimus Versus Azathioprine in a Cyclosporine and Ketoconazole–Based Immunosuppressive Therapy in Kidney Transplant: 3-Year Follow-up of an Open-Label, Prospective, Cohort, Comparative Clinical Trial

2010-01-01

Abstract: In cyclosporine-based protocols, everolimus is more effective than azathioprine to reduce acute rejection. Ketoconazole may reduce cyclosporine and everolimus requirements. We compared kidney transplant patients treated with everolimus or azathioprine in a ketoconazole- and cyclosporine-based immunosuppressive regimen.This open-label, prospective trial of low immunologic risk patients. Included one group (n = 11) who received everolimus (target blood level, 3–8 ng/mL) and the other (n = 11) azathioprine (2.0–2.5 mg/kg/d). Both received steroids, ketoconazole, and cyclosporine with C0 targets (ng/mL) in the everolimus group of 200–250, 100–125, and 50–65 for months 1 and 2 and thereafter and in the azathioprine group of 250–300 in month 1, 200–250 in month 2, 180–200 until month 6, and 100–125 thereafter.Their baseline characteristics were similar. Two biopsy-proven acute rejections occurred in each group. Three-year graft and patient survival in both groups was 100%. Creatinine clearances at months 6, 12, 24, and 36 were 63.7 ± 25.4, 58.9 ± 24.9, 56.0 ± 22.9, and 57.0 ± 27.6 in the everolimus group versus 72.6 ± 20, 68.6 ± 21.3, 71.4 ± 23.2, and 68.4 ± 19.2 in the azathioprine group (NS for every comparison).Major complications were rare and similar in both groups. Five patients in the everolimus group received simvastatin versus 4 in the azathioprine cohort (P = .53). The average cyclosporine doses to achieve targets were 0.8–1.2 mg/kg in the everolimus group and 1.6–2.2 mg/kg in the azathioprine group. The average everolimus dose after month 2 was 0.75–0.9 mg/d. We concluded that with cyclosporine, ketoconazole, and steroids, everolimus was as effective and safe as azathioprine. Cyclosporine reduction with everolimus did not influence graft survival or function at 3 years.

Impact of Recipient and Donor Nonimmunologic Factors on the Outcome of Deceased Donor Kidney Transplantation

M.F. Shaheen, F.A.M. Shaheen, B. Attar, K. Elamin, H. Al Hayyan, A. Al Sayyari — 2010-01-01

Abstract: Objective: To study the influence of nonimmunologic factors on the outcome of extended criteria deceased donor (DD) kidney transplants.Method: This is a retrospective study of DD transplantation carried out from January 1, 2003 to December 31, 2007, to investigate the impact on graft survival and function of donor renal function at retrieval, cold ischemia time (CIT), delayed graft function (DGF), acute rejection episodes (ARE), age, and weight of donors and recipients, transplant center activities, cause of donor death, donor-recipient gender pairing and size of the donating intensive care unit (ICU).Results: At retrieval, the frequency of donors with a creatinine clearance <60 mL/min, using the Cockcroft–Gault formula, and age >40 years were 31.7% and 32%, respectively. CIT > 24 hours, DGF, and ARE occurred in 27.1%, 33.4%, and 16.5% of cases, respectively. The overall 1- and 5-year graft and patient survival rates were 88% and 79.8% and 96.6% and 92.3%, respectively. The graft function was inferior with occurrences of ARE (P = .0001), DGF (P = .0001), CIT > 20 hours (P = .005), nontraumatic the donor death (P = .022), and donor ICUs bed capacity <20 (P = .03). The odds ratio (OR) for graft loss with DGF, ARE, and donors right kidneys were 7.74 (95% confidence interval [CI] 6–13.4; P = .0001), 4.47 (95% CI, 2.6–7.6; P = .0001) and 1.7 (95% CI, 1–2.8; P = .045), respectively. Graft function was not influenced by donor renal function at retrieval, donor weight, or donor– recipient gender pairings.Conclusion: CIT and ARE had an impact on both graft survival and function. DGF and cerebrovascular accidents as the cause of donor death negatively affected graft function during follow-up. ICU center experience had a positive impact on graft survival. Patient survival was affected by recipient age >50 years and female to male donation versus other gender pairings. Neither donor age nor acute terminal rise in the donor serum creatinine affected graft function or survival, or patient mortality.

Results of the Conversion to Everolimus in Renal Transplant Recipients With Posttransplantation Malignancies

2010-01-01

Abstract: Management of posttransplantation malignancies should include control of the neoplasia and preservation of renal function. Conversion to everolimus (EVL) would potentially have both effects. Twenty-one patients were converted to EVL due to posttransplantation neoplasms. We have presented herein descriptive data and postconversion (PC) outcomes among subjects of mean age 53.6 ± 10.1 years (range, 36–69), 57.1% were males, undergoing conversion at 108.2 ± 74.7 (range, 5–316) months after transplantation. All patients received standard immunosuppressive therapy and 9.5% had been induced with thymoglobulin. Malignant neoplasms were as follows: skin (n = 7), gynecological (n = 3), gastrointestinal (n = 3), PTLD (n = 2), renal (n = 2), CNS (n = 1), seminoma (n = 1), Kaposi's sarcoma (n = 1), and prostate cancer (n = 1). PC to EVL, calcineurin inhibitors (CNIs) were discontinued in 18 of 19 patients, mycophenolate in 9/12, and azathioprine in 5/7; all patients continued to receive steroids. In 16 patients (79%) tumors were removed. Chemotherapy was performed in 2 patients with PTLD and radiotherapy was performed in 1 patient with prostate cancer. Mean follow-up was 505 days (range, 59–1151); baseline glomerular filtration rate (GFR) was 53.5 ± 21.6 mL/min versus 48.5 ± 25.7 mL/min (P = not significant [NS]) at the last control. One patient experienced graft loss at day 744 after conversion due to chronic rejection. Adverse events were observed in 57% of patients and 28% displayed infections; no patient discontinued EVL. There were 2 deaths: 1 due to an infection and the other due to postsurgical complication. No deaths due to cancer progression were observed. The results observed in this series suggested that conversion to EVL for a posttransplantation neoplasm is a valid therapeutic alternative to preserve graft function and control disease progression.

Risk Factors for Urinary Tract Infections During the First Year After Kidney Transplantation

2010-01-01

Abstract: Introduction: Urinary tract infections (UTI) have been reported to occur with frequencies ranging from 30% to 60% in kidney transplant recipients during the first year posttransplantation. UTI is the main cause of infectious complications in this period. The objective of this study was to evaluate the incidence of UTI, during the first year posttransplantation and to identify the risk factors associated with its development, as well as its impact on graft function.Patients and Methods: This retrospective cohort study had as a primary outcome the development of UTI, defined as the presence of more than 100,000 colony-forming units (CFU) of a pathogenic organism by mL of urine. The univariate analysis was performed with chi-square test for categorical variables and Student t test for continuous ones metrics. We performed multivariate analysis with logistic regression. P < .05 was considered statistically significant.Results: We studied 176 kidney transplant recipients, including 54.5% of male gender and with an overall average age of 37 ± 12 years. The UTI incidence was of 35.8% (n = 63). The bacterium most frequently found in urine cultures was Escherichia coli (n = 46). In this study, the risk factors that were independently associated with UTI development were age, female gender, days of bladder catheterization, genitourinary anatomic alterations, and UTI during 1 month prior to kidney transplantation.Conclusion: This type of study makes it possible to identify risk factors and to formulate strategies focused on particular risk factors.

Thrombophilic Mutations: No Association With Thrombotic Events in Renal Transplant Recipients

2010-01-01

Abstract: Factor V Leiden and mutation of prothrombin gene G20210A have been associated with poor results in the early post–kidney transplantation period. Its long-term importance in stable patients has yet to be evaluated. We studied the prevalence of these inherited mutations and their relationship to thrombotic events in 82 Argentine renal transplant recipients with adequate long-term kidney function. In aggregate, 7.2% of patients were carriers of these mutations; however, their presence did not show any association with thrombotic events or renal function alterations. The routine evaluation for these mutations does not seem to be cost-effective in renal transplant patients.

Effectiveness and Cost of Replacing a Calcineurin Inhibitor With Sirolimus to Slow the Course of Chronic Kidney Disease in Renal Allografts

2010-01-01

Abstract: Renal grafts suffer a progressive decrease in glomerular filtration rate (GFR) because of several factors including calcineurin inhibitor (CNI) nephrotoxicity. Switching CNIs to sirolimus may improve this adverse prognosis. We performed a prospective, open-label clinical trial among 18 kidney transplant patients with more than 12 months of evolution (range, 385–1826 days), showing progressive GFR decreases and biopsies with interstitial fibrosis and tubular atrophy (IFTA). Immunosuppressive treatment included cyclosporine, ketoconazole, and steroids associated with azathioprine or mycophenolate mofetil. After signing an Institutional Review Board–approved written consent, cyclosporine was switched to sirolimus seeking to achieve a trough blood sirolimus concentration of 6–15 ng/mL. Wilcoxon and Student's t-tests were used to compare the values in the annual periods before and after the switch. GFR was estimated by the Modification of Diet in Renal Disease formula. There were no acute rejection episodes. Estimated GFR on the day of the switch was 38.0 ± 12.1 mL/min. After CNI switch, the slope of the estimated GFR significantly improved from −6.5 ± 9.2 to 8.1 ± 14.0 mL/min/year (P < .01). The estimated GFR 1 year after the switch was 47.2 ± 16.9 mL/min (P = .003 vs baseline). Total expenditures increased. The ratio of post-switch versus baseline total expenditures was 1.93 (95% confidence interval, 1.54–2.31) and the ratio of sirolimus to CNI cost was 2.16 (95% confidence interval, 1.53–2.78). Switching from CNI to sirolimus for kidney transplants with decreasing GFR and a biopsy with IFTA changes, suggesting progressive graft nephropathy, almost doubled total expenses. It is necessary to conduct trials using clinical end points to definitively validate this therapeutic intervention.

National Survey of Anemia Prevalence After Kidney Transplantation in Argentina

2010-01-01

Abstract: Anemia is prevalent in kidney transplant recipients and likely contributes to morbidity and mortality. The definition of anemia as established by the World Health Organization and subsequently adopted by the American Society of Transplantation is a hemoglobin concentration of 12 g/dL or less in women and 13 g/dL or less in men. Using this definition, the prevalence of anemia is nearly 30%. The National Survey of Post Transplant Anemia (PTA) in kidney transplant recipients in Argentina was conducted to evaluate the incidence of PTA at 1 year and its relationship to variables that influence transplantation outcome. At 1 year posttransplantation, mean (SD) hemoglobin concentration was 12.43 (1.77) g/dL (n = 379), hematocrit concentration was 38.26% (5.59%) (n = 379), serum creatinine concentration was 1.51 (0.72) mg/dL (n = 380), and creatinine clearance was 60.8 (22.47) mL/min (n = 334). The prevalence of PTA in Argentina at 1 year posttransplantation was 42.25%. At univariate analysis, female sex, immunosuppression regimen (mycophenolate mofetil plus mammalian target of rapamycin), and pediatric age group were associated with anemia. At multivariate analysis, only renal function and pediatric age group were associated with anemia. The mean hemoglobin level at year of transplant was 12.43 g/dL +/−1.77 and the prevalence of PTA in Argentina at year of transplant is 42.25%. Results of our survey show a correlation between Hb levels and graft function and pediatric recipient.

Chilean Experience in Liver Transplantation for Acute Liver Failure in Children

2010-01-01

Abstract: Background: Acute liver failure (ALF) in children is a life-threatening condition, associated with high mortality, and in almost one third of the cases, with no other therapeutic option than orthotopic liver transplant (OLT). The aim of this study was to present our experience with OLT for ALF in pediatric patients in Chile. Patients fulfilling the criteria for ALF who were transplanted in our centers were prospectively included in an excel Microsoft database. We analyzed demographics, etiology, surgical techniques, complications, and long-term results.Patients and Methods: Between 1994 and 2009, we transplanted 52 pediatric patients with ALF. The most frequent known etiology was acute hepatitis A in 9 cases (18%), but in 26 cases (50%) it was impossible to determine the etiology. Thirty- one patients were males (63%). The overall mean age was 7.5 years and the mean weight, 28.1 kg. Thirty-five (67%) received a cadaveric graft. Among them in 18 cases (34%) the liver had to be reduced but 17 (33%) received whole livers. There were 17 (33%) recipients of living-related livers. Twenty-two patients needed reoperation, including 13 due to surgical complications (59%) and 9 (41%) as planned interventions. Ten patients were retransplanted.Results: Actuarial survival of patients at 1 year was 80% and at 5 and 10 years, 72%. Graft survival at 1 year was 79%, at 5 years 69%, and at 10 years 50%.Conclusion: We have reported a series of pediatric liver transplant patients due to ALF whose results were comparable to other reported series. Living donor transplantation for ALF should be considered and offers a low morbidity rate without mortality.

Bridge Therapy in Hepatocellular Carcinoma Before Liver Transplantation: The Experience of Two Chilean Centers

2010-01-01

Abstract: Background: Orthotopic liver transplantation (OLT) is currently an established therapy for small, early-stage hepatocellular carcinoma (HCC) within the Milan criteria. Long waiting times due to the shortage of donor organs can result in tumor progression and drop-out from OLT candidacy. Therefore a wide variety of procedures are necessary before OLT. The aim of this retrospective study was to review our experience in relation to bridge therapy prior to OLT for HCC.Methods: This was a retrospective database review of all of the patient who underwent transplantation in our institutions between January 1993 and June 2009. We analyzed patients with a diagnosis of HCC in the explant.Results: Among 29 patients, including 12 who were diagnosed by the explant and 17 prior to transplantation, 88% underwent bridge therapy during a mean waiting time to OLT of 12 months. Among the 23 procedures, namely 1.5 procedures per patient, included most frequently chemoembolization (48%), alcohol ablation (30%), radiofrequency ablation (13%), and surgery (9%). Thirty-three percent of the explants contained lesions within the Milan criteria. In our series the 5-year survival rate for patients transplanted for HCC was 86%; in the bridge therapy group, it was 73%.Conclusions: The incidence of patients who underwent bridge therapy (52%) was similar to other reported experiences, but the fulfillment of Milan criteria in the explants was lower. Among the bridge therapy group, the survival was slightly lower, probably because this group displayed more advanced disease.

Liver Transplantation Results for Hepatocellular Carcinoma in Chile

2010-01-01

Abstract: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Liver transplantation is the best treatment for HCC; it improves survival, cures cirrhosis, and abolishes local recurrence. We describe the outcomes of patients with HCC who underwent liver transplantation in two liver transplantation centers in Chile.Methods: This study is a clinical series elaborated from the liver transplantation database of Pontificia Universidad Católica and Clínica Alemana between 1993 and 2009. The survival of patients was calculated using the Kaplan-Meier survival analysis. The significant alpha level was defined as 80%; however, the 5-year overall survival of patients who exceeded the Milan criteria in the explants was 66%. There was no difference in overall survival between patients transplanted for HCC versus other diagnosis (P = .548).Conclusion: This series confirmed that liver transplantation is a good treatment for patients with HCC within the Milan criteria.

Importance of Introduction of a Psychological Care Unit in a Liver Transplantation Unit

2010-01-01

Abstract: Background: Psychological changes in terminally ill patients with liver disease are underestimated. Therefore, a psychological care unit was introduced in the liver transplantation unit in a transplantation hospital in Spain.Objectives: To describe the establishment of the psychological care unit in a liver transplantation unit and to review its operation, and to evaluate and diagnose psychological changes in patients on the waiting list for liver transplantation.Materials and Methods: Variables evaluated included consultations, interviews, level of care provided, appointments postponed, difficulties, and cost-effectiveness.Psychopathologic symptoms were evaluated using the Symptom Assessment-45 questionnaire (Derogatis, 1975), examining 9 psychopathologic dimensions.Results: Thirty-eight patients were given an appointment, and 28 were interviewed. Twelve postponed the appointment. The level of support provided to patients on the waiting list was 70%. The hospital structure was used to develop the care unit, which is why it was only necessary to employ 1 professional psychologist. Of patients assessed, 54% exhibited relevant clinical symptoms of depression, and 47 demonstrated anxiety. Patients with symptoms of depression reported “loss of interest”; those with anxiety reported feeling “worried and tense.” Of these patients, an increased presence of symptoms was associated with various emotional problems such as hostility (33%), somatization (60%), obsession/compulsion (73%), interpersonal sensitivity (40%), phobic anxiety (20%), paranoid ideation (20%), and psychosis (6%).Conclusions: Patients on the waiting list for liver transplantation demonstrate increased clinical symptoms of depression and anxiety. Therefore, it is of great importance to introduce a psychological care unit to detect and treat these conditions. Introduction of the liver transplant unit program has improved multidisciplinary care and is cost-effective.

Conversion to Sirolimus Allows Preservation of Renal Function in Kidney and Kidney–Pancreas Allograft Recipients

G. Laham, S. Sleiman, G. Soler Pujol, C. Diaz, M. Dávalos, A. Vilches — 2010-01-01

Abstract: The major causes of graft failure are chronic allograft nephropathy (CAN) and patient mortality. Sirolimus (SRL) is a powerful immunosuppressant with a less nephrotoxic profile as well as a lower incidence of cancer. The aim of this study was to evaluate the impact of conversion to SRL from calcineurin inhibitor (CNI)-based therapy in kidney (KT) and kidney–pancreas (SPK) allograft recipients. We analyzed renal function, allograft and patient survival, and SRL-associated adverse effects in 93 adult patients (86 KT and 7 SPK), who were converted to SRL between January 2001 and November 2008. The main reason for conversion was CAN (76; 9%) and 52 (7%) were receiving tacrolimus. Conversion occurred at a median 26.2 months. There was a significant improvement in creatinine clearance (CCr) at 6 months after conversion (CCrbaseline 51.4 vs CCr6m 60.4 mL/min; P < .0001), without changes at 12 and 24 months. However, proteinuria increased significantly at 6 months compared with the baseline: 150 mg/24 hours (0–453) versus 0 mg/24 hours (range, 0–309), respectively (P < .0001), but did not progress at 12 or 24 months. At the same time we observed more extensive use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 60/5%; 65/3% and 70/2% at 6, 12, and 24 months. There were no changes in blood pressure control. Cholesterol significantly increased at 6 months (218.2 ± 37 vs. 186.6 ± 44 mg/dL; P < .0001). Graft and patient survivals at 4 years were 88% and 95%, respectively. Our experience suggested that conversion to SRL constituted a safe alternative with excellent results in patient and graft survival.

Pancreas Transplantation: Experience at University of Texas, Houston

A. Cicero, J.A. Lappin — 2010-01-01

Abstract: Introduction: Diabetes mellitus is a spectrum of diseases characterized by the absence of glycemic control and the development of secondary complications. Type 1 diabetes (insulin-dependent) accounts for a minority of cases, but it usually presents in younger age groups. This disease significantly affects quality of life.Methods: We retrospectively reviewed the cases of pancreas transplantation performed at University of Texas, Houston, from February 2008 to August 2009. All patients received immunosuppression induction with thymoglobulin (1.5 mg/kg). We used 3 drugs for maintenance: tacrolimus, mycophenolic acid, and prednisone. All patients received cytomegalovirus prophylaxis.Results: We transplanted 54 organs in 29 patients with type 1 diabetes mellitus. The mean patient age was 42 years. Patients had diabetes mellitus type 1 for an average of 28.82 years and were on dialysis for an average of 2 years. Nineteen patients were male (65%). Complications ensued in 68% of cases (20 patients), 9 of which required surgical exploration (31%). We lost 3 pancreatic allografts.Discussion: Pancreas transplant receipients constitute a unique population with a high risk of complications in the acute setting. During the first 3 months after simultaneous pancreas-kidney transplantation the relative mortality risk is increased but after a year it has clear advantage over diabetic patients on dialysis waiting for a transplant. To date, 26 patients have functional pancreatic allografts and 29 are dialysis-free. Pancreas transplantation is a challenging procedure. Surgeons must be prepared to aggressively manage the possible complications.

Importance of Technical Aspects in the Beginnings of a Pancreas Transplantation Program

2010-01-01

Abstract: Pancreas and kidney transplantation is the treatment of choice for patients with type 1 diabetes mellitus and terminal renal insufficiency. Herein we have presented a series of 35 patients transplanted between 2002 and 2009 including periods before and after 2007 divided based on introduction of some technical aspects.In the first phase (learning period) we have noted complications related to pancreatic surgery with a morbidity among 12 of 18 patients (66.6%). In the second period (stabilization period), complications appeared in 6 out of 17 patients (35.2%; P < .028). The reoperation rate was 83.3% in the learning period and 23.5% in the stabilization period (P < .03). Seven transplantectomies were performed in the first period (P < .004). Five patients died, all of them in the learning group (P < .019).Changes in the technical aspects of the procedure were responsible for improved outcomes obtained among pancreas and kidney transplantations.

Results of Heart Transplantation: 16 Years' Experience in a Center in Argentina

2010-01-01

Abstract: Heart transplantation (HTx) is the treatment of choice for advanced heart failure refractory to other treatments.Objective: To report the outcomes of patients undergoing orthotopic HTx in a center with 16 years' experience.Methods: We retrospectively examined the outcomes from three hundred nine HTx recipients between February 1993 and March 2009. The mean recipient age was 46 ± 16 years, and 80% were male. Ischemic cardiomyopathy was present in 37%; 43% (n = 133) were elective procedures and 57% (n = 176) were urgent/emergency procedures. The mean donor age was 26 years; their main cause of death was head/brain trauma. Survival was studied using Kaplan-Meier curves.Results: The global survival rates at 1, 5, 10, and 15 years were 80%, 74%, 71%, and 65%, respectively. Excluding losses during the first year after transplantation (conditional survival), the survival rate at 5 and 10 years reached 92% and 88.5%, respectively. The median follow-up was 7.7 years. The etiology and the urgent/emergency nature of the procedures did not show significant differences regarding the mortality rate (P = .8). The main causes of death were sepsis (28%) and primary nonfunction (18%). In-hospital mortality reached 16%. No significant differences were observed between the urgent/emergency versus the elective transplant procedures (P = .06). During the follow-up, the incidence of severe acute cellular rejection episodes was <3% after 5 years. The global incidence of antibody-mediated rejection reached 4.5%. Eleven subjects (3.5%) were diagnosed with post-transplantation lymphoproliferative disorder. During long-term follow-up, the incidences of kidney failure, diabetes mellitus, hypertension, and dyslipemia were 21%, 24%, 69%, and 70%, respectively. One percent required chronic dialysis.Conclusion: In our center, post-HTx survival rates at 1, 5, 10, and 15 years were 80%, 74%, 71%, and 65%, respectively, which were similar to those reported by the International Society of Heart and Lung Transplantation (ISHLT).

South American Heart Transplantation Registry of Patients Receiving Everolimus in Their Immunosuppressive Regimens

2010-01-01

Abstract: The increasing number of heart transplant recipients receiving immunosuppression with mammalian target of rapamycin inhibitors prompted the implementation of a South American Transplant Physicians Group to register these patients in a database. Everolimus (EVL) is a signal proliferation inhibition that reduces graft vascular disease when used de novo. Recently, its administration has expanded to subjects with resistant rejection or with side effects due to other immunosuppressive drugs (calcineurin inhibitors and/or steroids), allowing for better regulation of the immunosuppressive regimen. Herein we have shown the data collected from patients receiving EVL in ten South American Heart Transplant Centers. We have concluded that the administration of EVL is a useful adjunctive therapy that allows the reduction or suspension of other immunosuppressive drugs that caused unwanted side effects, without a loss of immunosuppressive efficacy, with manageable side effects, and constituting a valuable therapeutic option.

Everolimus in Lung Transplantation in Chile

M.T. Parada, A. Alba, C. Sepúlveda — 2010-01-01

Abstract: Everolimus has shown good results in kidney and heart transplantation, achieving low rates of rejection, of infections, and of tumors compared with calcineurin inhibitors (CNI). Some publications have shown beneficial effects in bronchiolitis obliterans syndrome (BOS). We have presented herein the initial experience with everolimus among lung allograft recipients in Chile.Methods: We retrospectively evaluated, charts of lung-transplanted patients who used everolimus (Certican) based on 2 years' follow-up, evaluating the indication for therapy; blood levels, rejection episodes, lung and kidney function, and side effects.Results: Eight of 55 lung transplantation patients were switched to everolimus, targeting a (mean drug level of 4.2 ng/dL), in combination with low-dose tacrolimus (mean levels 5.5 ng/dL) and steroids. The Reasons for conversion were: CNI nephropathy (n = 3), BOS (n = 4), and lymphoma (n = 1). In patients with renal dysfunction, serum creatinine had risen from 1.1 to 1.8 mg/dl, but at 3 months after everolimus conversion, they had returned to baseline values, maintaining that level for at least 2 years' follow-up. Patients with BOS had decreased their ventricular ejection fraction (VEF1) by 50%. Using everolimus, they maintained that VEF1 with little improvement. The patient with lymphoma died 11 months after conversion. No patient experienced a rejection episode, and they suffered from fewer infections than the other lung allograft recipients. There were no adverse events related to everolimus, but one patient discontinued the drug after 1 year owing to intolerance.Conclusion: Everolimus was effective to reverse CNI renal dysfunction in lung transplantation patients, possibly retarding the progression of BOS, without side effects over a 2-year follow-up.

Bronchiolitis Obliterans Syndrome Development in Lung Transplantation Patients

M.T. Parada, A. Alba, C. Sepúlveda — 2010-01-01

Abstract: The main cause of death in lung transplantation patients is chronic rejection, known as bronchiolitis obliterans syndrome (BOS). There are many variables associated with its appearance. The aim of this study was to identify factors associated with BOS and its impact on survival among lung transplantation patients.Methods: We retrospectively analyzed charts of lung transplant patients from 1999 to 2009, evaluating survival, BOS, and associated factors.Results: Fifty-six patients have been transplanted with a 5-year survival of 55%. Eighteen (32%) developed BOS, at a mean age at diagnosis of 57 years (range 16–74). According to BOS classification, seven patients (38.8%) were type 2 and six (33.3%) type 3. Half the patients developed BOS at a mean of 8.5 months after transplantation with a mean survival of 18.5 months (range 2–61). Among the factors analyzed, 13 patients (72%) displayed acute cellular rejection and nine (50%) gastroesophageal reflux disease (GERD) diagnosed by pHmetry, both of which were significantly associated with BOS (P = .005). Among seven lung transplantation patients with invasive cytomegalovirus disease, the four who developed BOS (P = .04) showed the worst survival (P = .05). Four of the six patients with severe BOS (66.6%) died at a mean of 10.6 months after the diagnosis. The main cause of death was respiratory insufficiency.Conclusions: BOS was associated with worse survival. The presence of acute cellular rejection episodes, CMV disease, and GERD were factors associated with chronic lung rejection.

Early and Late Infections in Lung Transplantation Patients

M.T. Parada, A. Alba, C. Sepúlveda — 2010-01-01

Abstract: Infections are an important cause of morbidity and mortality among transplanted patients. Their pathophysiology is associated with anatomic factors, immunosuppression, and pretransplant viral exposure. The aim of this investigation was to characterize infections following lung transplantation. We retrospectively analyzed the charts of 51 lung transplant recipients, who were transplanted between 1999 and 2008. Infections were classified according to their origin, etiology, occurrence time, and risk factors. The patient mean age was 55 years (range 13–71), 65% were male, and pulmonary fibrosis was the lung disease etiology in 59% of cases. Seventy-one episodes of infection were reported in the 51 patients, including (75%) during the first year after transplantation and 30 within the first 3 months (42%). Between the 4th and 11th months the number of infections decreased to 23 (32%), and afterwards there were 18 additional cases. The original site of infection was pulmonary in 43 episodes (60%), and the etiology was bacterial in 34 (48%), with Pseudomonas in 12 instances (35% of bacterial infections). Viruses were involved in 25 episodes, especially cytomegalovirus (CMV) in seronegative patients. The nine infections of fungal etiology (13%) were all caused by Aspergillus and always associated with either an acute rejection episode or suture damage. Three cases of tuberculosis were diagnosed, including two in the late post-transplant period. Three patients died of early infections.Conclusions: The critical period for infections in lung transplantation patients is the first 3 months, especially for those of bacterial etiology. CMV diseases were more common in seronegative patients and fungal infections in airway injury cases.

Mobilization and Collection of Peripheral Blood Stem Cells: Guidelines for Blood Volume to Process, Based on CD34-Positive Blood Cell Count in Adults and Children

2010-01-01

Abstract: We report 189 mobilizations and 489 collections of peripheral blood stem cells (PBSC) performed in 139 autologous transplantation patients and in 28 donors for allogeneic transplantations whose ages ranged from 2–68 years. We observed a correlation (P < .001; Pearson's coefficient 0.64) between CD34-positive cells and granulocyte-macrophage colony-forming units examined to estimate PBSC. In a subset of 287 collections (97 adults and 49 children) we obtained peripheral blood (PB) CD34-positive cell counts at 2 to 4 hours before leukapheresis. We noted a correlation between PB CD34-positive cell counts before leukapheresis and the number of CD34-positive cells per kilogram of body weight collected in the whole apheresis of the day (P < .001; Pearson's coefficient 0.82). An even better correlation was obtained between PB CD34-positive cells preapheresis and the yield of each individual blood volume (BV) processed (P < .001; Pearson's coefficient 0.87). Healthy donors and patients in each age group behaved similarly. In addition, the collection yield was greater among children than adults. These findings allowed us to develop a simple predictive model to estimate the BV to process for a target dose of CD34-positive cells per kilogram, based on the level of PBSC before apheresis in children and adults.

The Next Generation of Burns Treatment: Intelligent Films and Matrix, Controlled Enzymatic Debridement, and Adult Stem Cells

2010-01-01

Abstract: We describe a novel technology based on nanoengineered multifunctional acellular biologic scaffolds combined with wound dressings and films of the same kind. This method allows selective delivery and release of shielded biomaterials and bioactive substances to a desired wound or damaged tissue while stimulating the selective anchoring and adhesion of endogenous circulating repairing cells, such as mesenchymal stem cells, to obtain a faster and more physiologic healing process. We also present a new controlled enzymatic debridement process for more effective burned tissue scarolysis. In light of our preliminary in vitro and in vivo data, we are convinced that these approaches can include the use of other kinds of adult stem cells, such as endometrial regenerative cells, to improve the vascularization of the constructs, with great potential in the entire tissue and organ regeneration field but especially for the treatment of severely burned patients, changing the way these lesions may be treated in the future.

Comparison of Dissolution Properties of 2 Enteric-Coated Formulations Containing Mycophenolate Sodium: Myfortic vs Femulan

2010-01-01

Abstract: Enteric-coated tablets containing mycophenolate sodium have been developed to reduce gastric toxicity. The objective of this study was to compare 2 enteric-coated formulations containing 360 mg of mycophenolate sodium: the innovator product, Myfortic, and an agent that recently became available in Mexico, Femulan. For both formulations, mycophenolate sodium content was within the 90% to 110% range of the label claimed dose, and no impurities were present as determined at high-performance liquid chromatography. Mycophenolate sodium release was assayed by applying the US Pharmacopeia apparatus 2 dissolution test at 2 different pH values (1.2 and 6.8) to mimic conditions in the stomach and the small intestine, respectively. At pH 1.2, mycophenolate sodium release was less than 2%, with respect to the label claimed dose, for both formulations. At pH 6.8, mean (range) mycophenolate sodium release with Myfortic was 104.9% (104.0%–105.6%), and with femulan was 62.3% (51.3%–67.7%); the difference between formulations achieved statistical significance (P = .04). Moreover, intratablet variability with the generic formulation was unacceptable. Variation between the highest and lowest drug release was 32.0% for Femulan, and 1.02% for Myfortic. Thus, it is likely that Femulan results in insufficient and irreproducible absorption of mycophenolate sodium in the small intestine, leading to inadequate immunosuppressive efficacy. It is concluded that Femulan and myfortic are not equivalent formulations. Furthermore, Femulan is not a suitable formulation for clinical use in organ transplantation because it does not meet pharmaceutical quality standards.

Individualized Neoral Doses in Pediatric Renal Transplantation

Y. García, P. Muquillaza, S. Valdebenito — 2010-01-01

Abstract: We propose a model to calculate individualized Neoral doses based on individual oral clearance (CL/F)i and AUC(0–12h) values. The equation proposed by Dr. Ke-Hua Wu (2005), was employed to calculate the CL/Fi = 28,5 − (1.24*POD) − 0.252*(TBil-11) + 0,188*(Weight o-58) −0,191*(Age-42) − 2,42*INHI − 0,212*(HCT-28), where CI/F = (L/h), POD = postoperative days, Bil.T = total bilirubin level (umol/L), CBW = in kilograms, age = in years, INHI = concurrent metabolic inhibitors present (1) or absence (0), and HCT = hematocrit percentage.The AUC(0–12h) was calculated from the C2 value using the equation AUC(0–12h) = 815,578 + 4,44696*C2, derived from the linear correlation observed in earlier work at Clinica Las Condes Hospital.The studied population were 30 kidney transplanted children at Luis Calvo Mackenna Hospital, between 2002 and 2006, who were divided into 2 similar groups according to accurate C2 sampling time collections.The control group 1 was composed of 13 patients of age 9.85 ± 4 years whose samples were collected correctly. Group 2 was composed of 17 patients of age 10.43 ± 6 years with 252 C2 samples, which were obtained at medical control.All patients were under oral treatment with prednisone, azathioprine, nifedipine, and Neoral administered twice day according the weight of the patient and the C2 level.Relating Neoral administered doses to calculated doses according to the proposed model, the control group showed a linear correlation coefficient r = 0.924; r2 = 85.4%; (P < .05), and group 2, r = 0.54; r2 = 29.1 (P < .05).The proposed model to calculate Neoral doses had a predictive value of 85.0% when C2 samples were collected correctly.

Monitoring Cyclosporine Microemulsion at Two Hours Post Dosing in Pediatric Maintenance Liver Transplant Recipients

2010-01-01

Abstract: Cyclosporine absorption has been key to obtaining adequate results in immunosuppressive regimens. Since 2005, we have used a different monitoring program for Cyclosporine among pediatric liver transplant recipients namely, two hours post dosing concentrations (O2). This study of 128 patients included 50.8% males and 64.8% recipients of cadaveric livers. Their main reasons for transplantation were as follows: 43.8% acute liver failure and 37.5% biliary atresia. Mean age at time of transplantation was 5.4 ± 4.5 years for boys and 3.4 ± 3.3 years for girls. Mean age at the beginning of C2 monitoring was 8.9 ± 4.8 years and time elapsed since transplantation was 53.6 ± 36.4 months. The initial Cyclosporine dose of 5.5 ± 5 mg/kg/d had been reduced by month 24 to 4.5 ± 1.5 mg/kg/d. Estimation of glomerular filtration rate (eGFR) was performed using the Schwartz formula. Baseline creatinine and eGFR were 0.73 ± 0.49 mg/dL and 111.99 ± 28.27 mL/min.m2 versus 24-month creatinine and eGFR of 0.69 ± 0.20 mg/dL and 122.26 ± 24.47 mL/min.m2, respectively (P < .05). Eight patients experienced acute rejection episodes, 4 had chronic rejection, 3 posttransplantation proliferative diseases (PTLD) were reported, and 2 patients died. Cyclosporine C2 monitoring allowed a trend toward long-term dose reduction. Consequently we observed significant improvement in renal function. Acute/chronic rejection rates were low, which suggested that C2 monitoring was effective to control immunosuppressive therapy.The low incidence of PTLD and patient mortality showed that there was an adequate balance between safety and efficacy profiles.

Sirolimus in Kidney Transplant Donors and Clinical and Histologic Improvement in Recipients: Rat Model

2010-01-01

Abstract: Background: Ischemia-reperfusion (I/R) injury is one of the risk factors for delayed graft function, acute rejection episodes, and impaired long-term allograft survival after kidney transplantation. This antigen-independent inflammatory process produces tissue damage. Isogeneic transplantation in a rat model is a useful method for study of nonimmunologic risk factors for kidney damage.Objective: To study the effect of sirolimus on I/R injury using only 1 dose of the drug in the donor.Materials and Methods: Eighteen rats were allocated to 3 groups of 6 rats each: sham group, control group, and rapamycin group.Results: Improved renal function and systemic inflammatory response were observed in the rapamycin group compared with the control group (Δurea, Δcreatinine, and ΔC3, all P < .01). The number of apoptotic nuclei in the renal medulla in the control group was higher than in the rapamycin group (P < .01). Tubular damage was less severe in the rapamycin group compared with the control group (P < .01). Complement 3 and tumor necrosis factor-α expression in the kidney samples were significantly decreased when rapamycin was given to the donor rats (P > .01). Bcl-2 protein was upregulated in the rapamycin group compared with the control group (P < .01).Conclusion: Administration of rapamycin in donors attenuates the I/R injury process after kidney transplantation in a rat model.

Dendritic Cells and B Cells Cooperate in the Generation of CD4+CD25+FOXP3+ Allogeneic T Cells

2010-01-01

Abstract: Background: CD4+CD25+Foxp3+ regulatory T cells (Treg) play an essential role in immune tolerance, suppressing responses against self-antigens. Additionally, Treg play an important role in maintaining immunosuppression to alloantigens as well as to other antigens. It is well known that in the gut, a subset of dendritic cells produces retinoic acid (RA), which together with transforming growth factor (TGF-β) is able to differentiate naïve T cells into Treg. The aim of this study was to establish the role of antigen-presenting cells (APC) in the differentiation of allogeneic Tregs under the effect of RA and TGF-β.Methods: Splenic CD4+CD25− naïve T cells from C57BL/6 mice were co-cultured with splenic CD11c-enriched APC from Balb/c mice in the presence of TGF-β, RA, and interleukin (IL-2). After 6 days of culture, cells were analyzed for the expression of Foxp3 by flow cytometry. Additionally, we investigated the role of B cells and dendritic cells (DCs) and their stimulatory capacity in the generation of Tregs.Results: Our results showed that co-culture of naive T cells with the appropriate level of stimulation by APC in the presence of TGF-β, RA, and IL-2 provided a new powerful approach to generate allogeneic Treg cells. We demonstrated that although B cells and DCs can generate Tregs by themselves, a mixure of both APC improved their capacity to efficiently generate Tregs. Also, we observed that although the addition of IL-2 to the cultures was not crucial to generate Tregs, it was required to optimize their expansion and cell survival.

Induction of Tolerance in Renal Transplantation Using Splenic Transplantation: Experimental Study in a Canine Model

2010-01-01

Abstract: Objective: To evaluate in a canine model the induction of tolerance to renal transplantation after splenectomy and splenosis.Materials and Methods: This prospective, experimental, comparative, longitudinal study included 4 experimental groups, each comprising 4 dogs. Group 1 (control group) underwent renal transplantation only; group 2 underwent renal transplantation and splenectomy; group 3 underwent renal transplantation and splenosis; and group 4 underwent renal transplantation, splenectomy, and splenosis. Survival and degree of rejection were compared between the 4 groups.Results: Splenosis improved renal function after transplantation, as indicated by increased serum creatinine concentration (group 3, 6.2 mg/dL vs group 1, 12.9 mg/dL). Comparison of weighted survival curves (corrected for degree of rejection) demonstrated a significant difference between group 2 (66.0 days) and group 4 (66.2 days) vs group 1 (52.7 days) and group 3 (41.2 days) (P = .05, Wilcoxon rank sum test).Conclusion: These results suggest that in this experimental model of renal transplantation, splenosis and splenectomy induce clinical tolerance, as indicated by improved renal function and prolonged recipient survival.

Isolation of Viable Porcine Islets by Selective Osmotic Shock Without Enzymatic Digestion

2010-01-01

Abstract: Islet transplantation is a potential cure for type 1 diabetes, but clinical results have been disappointing. Currently, islet isolation is by enzymatic digestion of the pancreas which has significant pitfalls: warm ischemia exposure, collagenase-induced damage to the islet mass and viability, poor reproducibility, high cost, a relatively low number of islets obtained per whole pancreas, and selection of islets for collagenase resistance rather than for glucose responsiveness. In the present study we performed a series of experiments in a porcine model to demonstrate the feasibility of a new isolation method based on selective osmotic shock (SOS) using very high glucose solutions, doubling or tripling physiological osmotic strength. The SOS method can be carried out at room temperature or in the cold eliminating warm ischemia time which damages the islets. The SOS method does not depend on the texture of the pancreas so all pancreases can be processed identically and the process can be fully automated. The SOS method isolates all the islets of the pancreas regardless of size and shape allowing a greater number of islets to be harvested. The SOS method avoids exposure to toxins in collagenase solutions, is inexpensive and selects for islets with high concentrations of Glut 2 transporters, representing the best glucose responding islets. The SOS method showed a comparable recovery of islets from young pig pancreas and the islets showed improved viability. We conclude that the selective osmotic shock (SOS) method of separating islets from the pancreatic tissue is superior to the collagenase method.

Irregular Xenoantibodies Against Human Red Blood Cells in Papio anubis, P ursinus, P hamadryas, P papio, Saimiri sciureus, and Macaca mulatta: Possible Effect on Xenotransplantation Results

2010-01-01

Abstract: Objective: To assess the presence of irregular xenoantibodies against human red blood cells (RBCs) in 6 primate species used in xenotransplantation and other experimental procedures.Materials and Methods: Serum samples from 109 baboons of 4 different species (olive, chacma, sacred, and Guinea), 38 rhesus macaques, and 30 squirrel monkeys were tested for irregular xenoantibodies using an agglutination test using human RBCs of known phenotype for Rh, Kell, Kidd, Lewis, Lutheran, P1, and Duffy antigens, commercially available as RBC I, II, and III.Results: We found hemagglutination for RBC I in 49%, 22%, 100%, 57%, 32%, and 33% of olive, chacma, sacred, and Guinea baboons, rhesus macaques, and squirrel monkey, respectively. The frequency for RBC II was 49%, 50%, 100%, 57%, 37%, and 33%, respectively, and for RBC III was 56%, 37%, 100%, 79%, 34%, and 33%, respectively. There were differences in frequency depending on the sex of the rhesus macaques; all 3 RBCs tested were higher in the females: 44% vs 0%, P = .008; 48% vs 1%, P = .02, and 44% vs 9.1%, P = .04 for RBC I, II, and III, respectively. There were differences due to age in only olive baboons, and a higher frequency in younger animals compared with juvenile, subadult, and adult animals for all 3 human RBCs.Conclusions: Assessment of irregular antibodies in the presence of primate serum should be taken into account during any experimental xenotransplantation protocol.

Prophylaxis and Treatment of Chagas Disease in Renal Transplant Donor and Recipient: Case Report

A.M. Ortiz, P. Troncoso, M. Sainz, S. Vilches — 2010-01-01

Abstract: Chagas disease is a prevalent zoonosis in Latin America, caused by the protozoa Trypanosoma cruzi and transmitted by Triatoma infestans. Part of the infectious cycle consists of chronic subclinical parasitemia, causing in the long term end-organ damage. Amastigotes have been isolated from various organs including native and allograft renal parenchyma; thus, transplantation plus immunosuppression therapy is another mode of disease transmission and reactivation. Herein, we report 2 successful kidney transplantations cases in which either infection or reactivation was averted using prophylactic nitroderivates.

Author Index

2010-01-01

Transplantation Proceedings

Editorial Board

Contents

Long-Term Outcomes of Short Bowel Syndrome Requiring Long-Term/Home Intravenous Nutrition Compared in Children With Gastroschisis and Those With Volvulus

Chronic Intestinal Pseudo-Obstruction Related to Viral Infections

Natural History of Intestinal Failure Induced by Chronic Idiopathic Intestinal Pseudo-Obstruction

Cambridge-Miami Score for Intestinal Transplantation Preoperative Risk Assessment: Initial Development and Validation

Review of the Diagnoses Predisposing Infants to Intestinal Failure on Hospitalized Parenteral Nutrition

Sepsis and Its Etiology Among Hospitalized Children Less Than 1 Year of Age With Intestinal Failure on Parenteral Nutrition

Preliminary Experience With Alemtuzumab Induction Therapy Combined With Maintenance Low-Dose Tacrolimus Monotherapy in Small-Bowel Transplantation in China

Daclizumab and Alemtuzumab as Induction Agents in Adult Intestinal and Multivisceral Transplantation: Rejection and Infection Rates in 40 Recipients During the Early Postoperative Period

Comprehensive Surgical Intestinal Rescue and Transplantation Program in Adult Patients: Bologna Experience

Psychological Adaptation and Quality of Life of Adult Intestinal Transplant Recipients: University of Bologna Experience

International Grading Scheme for Acute Cellular Rejection in Small-Bowel Transplantation: Single-Center Experience

Citrulline Evaluation in Bowel Transplantation

Evaluation of Calprotectin Level in Intestinal Content as an Early Marker for Graft Rejection

Gene Expression Profiling of MicroRNAs in Small-Bowel Transplantation Paraffin-Embedded Mucosal Biopsy Tissue

Monitoring Cytomegalovirus T-Cell Immunity in Small Bowel/Multivisceral Transplant Recipients

Early and Late Virological Monitoring of Cytomegalovirus, Epstein-Barr Virus, and Human Herpes Virus 6 Infections in Small Bowel/Multivisceral Transplant Recipients

Thrombotic Microangiopathy Following Intestinal Transplantation: A Single Center Experience

Mycophenolate Mofetil–Related Gastrointestinal Mucosal Injury in Multivisceral Transplantation

Evaluation of Hemodynamic, Metabolic, and Electrolytic Changes After Graft Reperfusion in a Porcine Model of Intestinal Transplantation

Immediate Antibody-Mediated (Hyperacute) Rejection in Small-Bowel Transplantation and Relationship to Cross-Match Status and Donor-Specific C4d-Binding Antibodies: Case Report

Outcome of Exfoliative Rejection After Isolated Intestinal Transplantation in an Adult: Case Report

Esophageal Varices in Chronic Intestinal Insufficiency in Absence of Portal Hypertension or Liver Cirrhosis: Case Report

World Day of Organ Donation and European Day of Organ Donation

Preface

The PIERDUB Project: International Project on Education and Research in Donation at University of Barcelona: Training University Students About Donation and Transplantation

A National Program Toward Improving Renal Health: Advancing Organ Donation Awareness

Donor Compensation: An Ethical Imperative!

Attitude of Health Care Professionals to Organ Donation: Two Surveys Among the Staff of a German University Hospital

Organ Transplant Education: The Way to Form Altruistic Behaviors Among Secondary School Students Toward Organ Donation

Health Content Analysis of Organ Donation and Transplantation News on Turkish Television Channels and in Turkish Print Media

The Role of an Interdisciplinary Transplant Team on Living Donation Kidney Transplantation Program

The Rate of Organ and Tissue Donation After Brain Death: Causes of Donation Failure in a Romanian University City

Presumed Consent for Organ Donation: Is Romania Prepared for It?

Functional Improvement Between Brain Death Declaration and Organ Harvesting

The Donor Action Project: A Valuable Tool to Measure Quality and Efficacy of the Donation Process in Emilia-Romagna

Machine Perfusion Preservation for Kidney Grafts With a High Creatinine From Uncontrolled Donation After Cardiac Death

New Insights Into Fatty Liver Preservation Using Institute Georges Lopez Preservation Solution

A Fast and Safe Living Donor “Finger-Assisted” Nephrectomy Technique: Results of 359 Cases

Deceased Donor Organ Transplantation With Expanded Criteria Donors: A Single-Center Experience From India

Liver Transplantation Utilizing Old Donor Organs: A German Single-Center Experience

Preprocurement Pancreas Allocation Suitability Score Does Not Correlate With Long-Term Pancreas Graft Survival

European Homograft Bank: Twenty Years of Cardiovascular Tissue Banking and Collaboration With Transplant Coordination in Europe

Tissue Procurement System in Japan: The Role of a Tissue Bank in Medical Center for Translational Research, Osaka University Hospital

Protective Effects of N-Acetylcysteine on the Liver of Brain-Dead Ba-Ma Mini Pig

Terlipressin as Rescue Therapy in Catecholamine-Resistant Hypotension in Solid Organ Donors: A Case Report

Review of the Uruguayan Kidney Allocation System: The Solution to a Complex Problem, Preliminary Data

Spanish and Latin American Nursing Personnel and Deceased Organ Donation: A Study of Attitude

Level of Acceptance of a Clinical Solid Organ Xenotransplantation Program Among Personnel in Organ Transplant-Related Services in Spanish, Mexican, and Cuban Hospital Centers

Attitudes Toward Living Kidney Donation in Transplant Hospitals: A Spanish, Mexican, and Cuban Multicenter Study

Attitudes of Spanish and Mexican Resident Physicians Faced With Solid Organ Donation and Transplantation

Organ Donation and Transplantation Training for Future Professional Nurses as a Health and Social Awareness Policy

Effects of Immunosuppressive Drugs on Rat Renal Ischemia Reperfusion Injury

Evaluation of the Stages Involved in Cold Ischemia Time in Renal Transplants in Chile

Evaluation of Late Immunologic Parameters Among Renal Transplant Recipients Induced With Campath-1H

Pharmacogenetics of Immunosuppressant Polymorphism of CYP3A5 in Renal Transplant Recipients

Prediction of Renal Function After Living Donor Kidney Transplantation

Parameters of Doppler Ultrasound at Five Days Posttransplantation as Predictors of Histology and Renal Function at One Year

Evaluation of HLA Matchmaker Compatibility as Predictor of Graft Survival and Presence of Anti-HLA Antibodies

Everolimus Versus Azathioprine in a Cyclosporine and Ketoconazole–Based Immunosuppressive Therapy in Kidney Transplant: 3-Year Follow-up of an Open-Label, Prospective, Cohort, Comparative Clinical Trial

Impact of Recipient and Donor Nonimmunologic Factors on the Outcome of Deceased Donor Kidney Transplantation

Results of the Conversion to Everolimus in Renal Transplant Recipients With Posttransplantation Malignancies

Risk Factors for Urinary Tract Infections During the First Year After Kidney Transplantation

Thrombophilic Mutations: No Association With Thrombotic Events in Renal Transplant Recipients

Effectiveness and Cost of Replacing a Calcineurin Inhibitor With Sirolimus to Slow the Course of Chronic Kidney Disease in Renal Allografts

National Survey of Anemia Prevalence After Kidney Transplantation in Argentina

Chilean Experience in Liver Transplantation for Acute Liver Failure in Children

Bridge Therapy in Hepatocellular Carcinoma Before Liver Transplantation: The Experience of Two Chilean Centers

Liver Transplantation Results for Hepatocellular Carcinoma in Chile

Importance of Introduction of a Psychological Care Unit in a Liver Transplantation Unit

Conversion to Sirolimus Allows Preservation of Renal Function in Kidney and Kidney–Pancreas Allograft Recipients

Pancreas Transplantation: Experience at University of Texas, Houston

Importance of Technical Aspects in the Beginnings of a Pancreas Transplantation Program

Results of Heart Transplantation: 16 Years' Experience in a Center in Argentina

South American Heart Transplantation Registry of Patients Receiving Everolimus in Their Immunosuppressive Regimens

Everolimus in Lung Transplantation in Chile

Bronchiolitis Obliterans Syndrome Development in Lung Transplantation Patients

Early and Late Infections in Lung Transplantation Patients