Transplantation Proceedings

Editorial Board

2011-12-01

Repairing the Chronic Damaged Kidney: The Role of Regenerative Medicine

H.C. Caldas, A.P.C. Hayashi, M. Abbud-Filho — 2011-12-01

Abstract: The increasing number of patients who suffer from chronic kidney diseases combined with the organ shortage have directed the attention of researchers to new alternatives in the fields of regenerative medicine including cell-based therapies and tissue bioengineering. This review of renal regenerative medicine addresses the mechanisms of action by stem cells to regenerate or repair chronically damaged renal tissue, alternative routes for their delivery, the role of biomaterials in tissue engineering, and the potential therapeutic effects of combining cell therapy with biomaterials. Despite the promise of ongoing work for therapy of chronic renal failure, caution is required as a large gap still exists between scientific knowledge and clinical translation for safe, effective stem cell-based therapies.

Oxidative Stress and Renal Interstitial Fibrosis in Patients After Renal Transplantation: Current State of Knowledge

K. Kędzierska, M. Domański, K. Sporniak-Tutak, B. Dołęgowska, K. Ciechanowski — 2011-12-01

Abstract: Long-term outcomes in renal transplantation has represented a major challenge for transplantologists and nephrologists for many years. The use of a new generation of immunosuppressive drugs has contributed to reducing the incidence of acute rejection episodes, but chronic allograft nephropathy is the cause of renal allograft loss in ∼50% of recipients. Organ fibrosis is the main histopathologic finding in those cases. Many researchers have focused on mechanisms leading to fibrosis. It is thought that an explanation of the pathologic mechanism of this phenomenon may improve long-term effects of therapy for kidney transplant recipients.

Living-Donor Liver Transplantation: Impact on Donor's Health-Related Quality of Life

L. Kousoulas, N. Emmanouilidis, J. Klempnauer, F. Lehner — 2011-12-01

Abstract: Objective: The aim of this study was to evaluate the health-related quality of life of living liver donors after living-donor liver transplantation (LDLT). Methods: Health-related quality of life (HRQOL) in 55 living liver donors operated on at our center between 2002 and 2009 was assessed using the German Version of the 36-Item Health Survey (SF-36). Results: Donors after full right-lobe hepatectomy (n = 18) scored similarly to and without statistically significant difference from the German reference population, whereas donors after left lateral segmentectomy (n = 37) revealed statistically significant higher average score values (P < .005) in the categories of physical functioning, bodily pain, and general health compared with the German reference population. In the analysis between donors after full right-lobe hepatectomy and donors after left lateral segmentectomy no statistically significant difference was observed in any of the SF-36 categories. Postoperative complications of the donors and postoperative recipient mortality were particularly revealing regarding HRQOL. Donors who developed postoperative complications presented a lower HRQOL, especially in the categories of role physical, bodily pain, and social functioning, where statistically significant differences (P < .005) were observed. Similarly, postoperative recipient mortality correlated with lower mean score values in all SF-36 categories, but a statistically significant difference (P < .005) was reached only in the categories of role emotional and mental health. Conclusions: Donors did not regret their decision to donate, because HRQOL was not negatively affected by the donation procedure. Living liver donors scored as well as or even better than the German reference population, but it was clearly shown that the development of postoperative donor complications and the postoperative recipient mortality had a negative effect on the HRQOL of donors.

Is Single-Shot Epidural Analgesia More Effective Than Morphine Patient-Controlled Analgesia for Donor Nephrectomy?

Z. Milan, S. Das, M. Kocarev, V. Rawari — 2011-12-01

Abstract: Objective: We compared single-shot epidural analgesia (20 mL 0.125% levobupivacaine and 3 mg diamorphine) followed by regular tramadol versus morphine patient-controlled analgesia (PCA) for postoperative pain following donor nephrectomy. Methods: We retrospectively evaluated 12 patients who received single-shot epidural analgesia (SSE group) before anesthesia induction, followed by regular tramadol, and 14 patients who received morphine PCA (PCA group) for postoperative pain after donor nephrectomy. Postoperative pain scores were recorded at 0, 1, 12, 24, and 48 hours after nephrectomy. We also collected data regarding morphine consumption, additional analgesia, nausea, antiemetic use, time to oral intake, mobilization, and discharge. Results: The 2 groups were similar for age, gender, body mass index, American Society of Anesthesiologists status, duration of surgery, laparoscopic/open nephrectomy ratio, and intra- and postoperative additional analgesia. There were no significant between-group differences in pain and nausea scores. The SSE group showed lower intra- and postoperative antiemetic use than the PCA group (25% vs 78.5% and 1 dose vs 2.5 doses, respectively; P < .05). The average time to oral fluid and solid food intake and for assisted mobilization were similar in the 2 groups. However, independent mobilization and hospital discharge were significantly sooner in the SSE group (34 hours vs. 47.4 hours; [P < .05] and 3.7 days vs 4.7 days [P < .05], respectively). Conclusions: In this small pilot study, SSE with 20 mL 0.125% levobupivacaine and 3 mg diamorphine, followed by regular tramadol, provided postoperative analgesia similar to morphine PCA. However, patients in the SSE group used less antiemetic medication, were independently mobile earlier, and were discharged from the hospital earlier than patients in the PCA group.

Laparoscopic Live-Donor Nephrectomy: A Comparison with the Open Technique and How to Reach Quality Standards: A Single-Center Experience in Thailand

2011-12-01

Abstract: Objective: We report our experience with laparoscopic donor nephrectomy (LDN) compared with open donor nephrectomy (ODN). Prognostic factors associated with adverse outcomes in LDN were identified. Methods: From January 2000 to December 2009, 243 consecutive live-donor nephrectomies were performed, including 129 LDNs and 114 ODNs. We compared patient demographics, perioperative outcomes, and recipient graft function in each group. Prognostic factors for adverse outcomes in LDN were investigated using uni- and multivariate analyses. Results: Patient demographics, except mean donor age (P = .032), were similar between groups. Mean operative time (219 vs 163 minutes; P < .001) and warm ischemia time (WIT; 3.1 vs 1.7 minutes; P < .001) were significantly longer in LDN. Conversely, mean analgesic requirement (9.2 vs 14.7 mg morphine; P < .001) and postoperative hospital stay (6.5 vs 7.1 days; P = .003) were significantly lower with LDN. Mean estimated blood loss (EBL) was slightly lower in LDN (P = .15). There were 7 conversions from LDN to ODN. Complication rates were similar between the groups (P = .38). Delayed graft function (10.9% vs 1.7%; P = .016) and mean serum creatinine level at 1 month (1.47 vs 1.3 mg/dL; P = .04) were higher for LDN. However, 5-year allograft survival was not inferior among LDN (90% vs 85%; P = .42). Mean operative time (268 to 175 minutes; P < .001), EBL (316 to 66 mL; P < .001), and complication incidence (8 to 0 cases; P < .002) gradually decreased from the initial 43 cases to the last 43 cases of LDNs. Among surgeons who had performed-30 LDNs, the mean operative time and WIT were 197 mL and 2.8 minutes, respectively. Conclusions: Based on our evidence, LDN was a feasible and safe surgical option for live-donor nephrectomy, even in a small volume center. Better results can be achieved after a learning curve of experience for both the surgeon and the institution.

Public Opinion on Renal Transplantation in Brunei Darussalam

T.T. Teo, M.M. Hossain, S. Zinna, Y.P. Liew, J. Tan — 2011-12-01

Abstract: Brunei Darussalam is a small Muslim country with a high prevalence and incidence of kidney disease. At present, there is no local transplant program for patients on the renal replacement therapy program. In order to assess feasibility of a local transplant program, we decided to conduct a survey to assess public opinion on renal transplantation. The majority of the 300 respondents (78.7%) were willing to donate their kidneys if needed. Even after learning of the small theoretical risks of kidney failure, 72.33% of all respondents were still willing to proceed with transplantation. Respondents who had relatives on dialysis and who had a higher education level were more willing to donate their kidneys. There was no significant difference between Muslims and non-Muslims. Most respondents (59.7%) preferred to have transplantation done locally. This study shows that most Bruneians are receptive of the idea of living related kidney donations, which augurs well for the sustainability of a new program. More work is needed to overcome other barriers like the availability of surgical expertise and facilities and cost-benefit considerations.

Effects of n-3 Polyunsaturated Fatty Acids on Rat Livers after Partial Hepatectomy via LKB1-AMPK Signaling Pathway

X.P. Yan, S. Wang, Y. Yang, Y.D. Qiu — 2011-12-01

Abstract: Objective: n-3 polyunsaturated fatty acid (n-3 PUFA) are considered to be associated with liver regeneration. We investigated the effects of n-3 PUFA on hepatic tight junction (TJs) and liver regeneration after 70% partial hepatectomy (PH) in rats. Methods: Male Sprague-Dawley rats were divided into four groups: sham group; control group, fish oil (FO; 1 mL/kg), and the FO (2 mL/kg) group. We examined changes in expression of hepatic TJs by at confocal microscopy in liver regeneration by routine clinical chemistry methods for hepatic function, and in activation of liver kinase B1–adenosine monophosphate–activated protein kinase (AMPK) signaling pathway. Using Western blot analysis. Results: After PH survival was higher in the FO than the control group. We observed treatment with n-3 PUFA to activated the LKB1-AMPK signaling pathway as well as to earlier, stronger and prolonged of the expression of Occludin, Claudin-3, zonula occludens-1, and proliferating cell nuclear antigen proteins. In addition, hepatic TJ structures and the level of liver function were protected after n-3 PUFA treatment. Conclusions: After PH in rats, n-3 PUFA enhanced expression and protected the structure of hepatic TJs via the LKB1-AMPK signaling pathway. Moreover, it may promote liver regeneration partly via the LKB1-AMPK signaling pathway. It protected postoperative hepatic function and may be a liver protective agent against liver failure.

Potential Protective Effect of Nuclear Factor-κB Decoy Oligodeoxynucleotides on Endotoxin-induced Liver Injury

J.D. Li, Y. Peng, Q. Li, J.W. Xiao, J.P. Gong, Z.J. Liu — 2011-12-01

Abstract: Purpose: We sought to study the protective effects of nuclear factor–κB decoy oligodeoxynucleotides (ODNs) on endotoxin-induced liver injury in a rat model. Methods: Sixty Sprague-Dawley rats were randomly divided into a control (n = 20), a lipopolysaccharide (LPS) (n = 20), and an NF-κB decoy ODN group (n = 20). Liver and blood serum samples were collected at 24 hours after the operation. NF-κB binding activity was detected by an electrophoretic mobility shift assay, liver histopathology, by light microscopy; and cell apoptosis, by a terminal-deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay. The serum of liver enzyme (aspartate transaminase [AST]) levels were measured using an automated biochemical analyzer and tumor necrosis factor (TNF)–α and interleukin (IL)-6 by enzyme-linked immunosorbent assays. Results: NF-κB was dramatically activated after endotoxin-induced liver injury. Many hepatocytes underwent degeneration and necrosis in the LPS group. The expressions of AST, TNF-α, and IL-6 were significantly increased compared with the control group (P = .0005), However, NF-κB decoy ODNs altered these undesirable changes. On the other hand, IL-6 expression was not significantly decreased by the NF-κB decoy versus the LPS group (P = .0745). Conclusions: NF-κB decoy strategy inhibited the binding activity of NF-κB, thus suppressing production of downstream cytokines which play crucial roles in protection from endotoxin-induced injury.

Erythropoietin Attenuates Apoptosis After Ischemia-Reperfusion–Induced Renal Injury in Transiently Hyperglycemic Wister Rats

2011-12-01

Abstract: Background: Hyperglycemia is associated with a decreased tolerance to ischemia and an increased severity of renal ischemia reperfusion (I/R) injury. It has been suggested that erythropoietin (EPO) attenuates this effect in normoglycemic animals. This study sought to examine the effects of EPO on treatment renal I/R injury (IRI) in transiently hyperglycemic rats. Material and Methods: Twenty-eight male Wister rats anesthetized with isoflurane received glucose (2.5 g.kg−1 intraperitoneally) before right nephrectomy. They were randomly assigned to four groups: sham operation (S); IRI (ISO); IRI+EPO, (600 UI kg−1 low-dose EPO [EL]); and IRI+EPO 5000 UI kg−1 (high-dose EPO [EH]). IRI was induced by a 25-minute period of left renal ischemia followed by reperfusion for 24 hours. Serum Creatinine and glucose levels were measure at baseline (M1), immediately after the ischemic period (M2), and at 24 hours after reperfusion (M3). After sacrificing the animals, left kidney specimens were submitted for histological analysis including flow cytometry to estimate tubular necrosis and the percentages of apoptotic, dead or intact cells. Results: Scr in the ISO group was significantly higher at M3 than among the other groups. Percentages of early apoptotic cells in ISO group were significantly higher than the other groups. Percentages of late apoptotic cells in S and ISO groups were significantly greater than EL and EH groups. However, no significant intergroup differences were observed regarding the incidence of tubular necrosis. Conclusions: Our results suggested that, although not preventing the occurrence of tubular necrosis, EPO attenuated apoptosis and glomerular functional impairment among transiently hyperglycemic rats undergoing an ischemia/reperfusion insult.

Protective Effects of Neutrophil Gelatinase–Associated Lipocalin on Hypoxia/Reoxygenation Injury of HK-2 Cells

L.Y. Cui, S. Yang, J. Zhang — 2011-12-01

Abstract: Background: Neutrophil gelatinase–associated lipocalin (NAGL) was first extracted from neutrophil granules. Our previous study showed that the expression of NGAL mRNA and protein can be induced by hypoxia/reoxygenation. This study was designed to investigate the relationship between NGAL and hypoxia/reoxygenation injury pathologies in HK-2 cells. Methods: The effect of NGAL on the proliferation of HK-2 cell lines was analyzed with a MTT colorimetric assay. Cell-cycle distribution and measurement of the percentage of apoptotic cells were performed by flow cytometry after stained with propidium iodide and annexin V–fluorescein isothiocyanate. The expression of genes for apoptotic proteins Bcl-2, Bax, and caspase-3 was analyzed with real-time reverse-transcription polymerase chain reaction (RT-PCR). The expression of NGAL mRNA and protein was analyzed with real-time RT-PCR or Western blot, respectively. Results: HK-2 cells were treated with hypoxia/reoxygenation. HK-2 cells exhibited an increase in the number of cells in the G0/G1 phase and a decrease in the number of cells in the S and G2/M phases. The proliferation index is decreased. When HK-2 cells were treated with 200 ng/mL recombinant NGAL and hypoxia/reoxygenation, there were no effects on cell-cycle distribution. The ratio of early apoptotic cells in the control and hypoxia/reoxygenation groups were 1.1% and 26.5%, respectively. After the addition of 200 ng/mL recombinant NGAL, the ratio of early apoptotic cells in the hypoxia/reoxygenation group dropped to 19.6%. The expression of Bax/Bcl-2 ratio and caspase-3 were significantly higher in the hypoxia/reoxygenation compared with the control group. After the addition of 200 ng/mL recombinant NGAL, the levels of Bax/Bcl-2 ratio and caspase-3 decreased significantly compared with the control group. Conclusions: The action of NGAL against hypoxia/reoxygenation injury was due to inhibiting the apoptosis via inhibition of the expression of the genes of proapoptotic proteins Bax, Bcl-2, and caspase-3.

Activations of Mitogen-Activated Protein Kinases and Regulation of Their Downstream Molecules After Rat Lung Transplantation from Donors After Cardiac Death

2011-12-01

Abstract: Objectives: Accepting organs donated after cardiac death (DCD) is an effective approach to the donor shortage. However, lung transplantations from DCD donors show severe rapid pulmonary graft dysfunction (PGD) followed by warm ischemia–reperfusion injury (IRI). This study sought to clarify the molecular mediators in warm IRI, including activation of mitogen-activated protein kinase (MAPK) and the downstream cascades. Methods: We performed single left lung transplantation using organs from male Sprague-Dawley rats after 0 (CIT group), 30 (30WIT group), or 180 (180WIT group) minutes of warm ischemia time. Pulmonary graft functions were estimated by blood gas analysis. At 1 hour after reperfusion, the phosphorylation status of MAPKs (ERK, p38, and JNK) and the gene expression levels of transcription factors (Egr-1 and ATF-3) and immune mediators (MCP-1, MIP-2, PAI-1, ICAM-1, TNF-α, IL-1β, IL-6, and COX-2) in the grafts were examined using Western blotting and real-time polymerase chain reaction assays. Results: Severe PGD was observed in the 180WIT group compared with transplanted lungs in the other groups, which exhibited good pulmonary graft function. ERK and JNK activations, as well as mRNA levels of transcription factors (Egr-1 and ATF3) significantly increased with greater warm ischemic times. The pattern of JNK activation correlated with the severity of PGD. MCP-1, ICAM-1, IL-1β, IL-6, and COX-2 were also up-regulated among the 180WIT group, although MIP-2 and PAI-1 showed no significant differences among the groups. Conclusions: We suggest that the ERK and JNK pathways may play important roles to induce the injury caused by prolonged warm ischemia followed by reperfusion in the setting of lung transplantation from DCD donors.

Relationship Between Ischemia/Reperfusion Injury and the Stimulus of Fibrogenesis in an Experimental Model: Comparison Among Different Preservation Solutions

2011-12-01

Abstract: Background and Aims: Orthotopic liver transplantation (OLT) has been the standard treatment for end-stage acute and chronic liver disease. Ischemia-reperfusion (I/R) injury is one of the major causes of poor graft function early after OLT, and adversely influencing graft and patient survivals. It is unknown whether I/R injury influences liver fibrogenesis. Materials and Methods: Livers from 25 adult male Wistar rats were randomly assigned into 5 experimental groups according to the preservation solution: saline solution (SS); University of Wisconsin (UW) solution; Fructose 1, 6-biphosphate (FBP); S-Nitroso-N-Acetylcysteine (SNAC): or UW + SNAC (SNAC+UW). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH) were determined in preservation solution samples at 2, 4, and 6 hours. After 6 hours of cold ischemia, ex situ reperfusion was applied to the liver for 15 minutes. Serum AST, ALT, LDH, and renin levels were determined. Fresh liver slices were processed for histological studies, determination of thiobarbituric acid reactive substances, catalase, and glutathione, and expression of TGF-β1 and angiotensin II AT1 receptor. Results: AST was significantly lower during cold storage with UW than with the older media (P = .001); ALT was lower in the FBP group (P = .023) and LDH was lower in the FBP and SNAC groups (P = .007). After reperfusion, serum AST, ALT, LDH, and TBARS showed no significant differences among the groups. Catalase was significantly lower in the SS and FBP groups (P = .008 and P = .006, respectively). Compared with UW, glutathione concentrations were significantly higher in SS, FBP, and SNAC 200 (P = .004). Renin levels were significantly lower in the FBP group (P = .022). No histological signs of preservation injury were observed in the hepatic sample. No expressions were detected of TGF-β1 or AT1 receptor. Conclusion: In this experimental model of early reperfusion injury, preservation changes related to higher levels of renin, which suggest its role in fibrogenesis. FBP was associated with lower renin levels than other solutions including UW.

Acceptable Warm Ischemia Time of Tracheal Grafts From Non–heart-beating Donors in Rats

J.-Q. Han, K. Zhang, J. Cui, C. Liu, G.-B. Zhao, Y.-Z. Xin — 2011-12-01

Abstract: Objectives: Warm ischemia (WI)-induced airway complications are common in clinical lung transplantation. However, the acceptable WI time of tracheal grafts from non–heart-beating donors (NHBDs) is unknown. The purpose of this study was to determine the acceptable WI time by observing tracheal epithelial regeneration among NHBD. Method: Forty-eight rats were randomly divided into four groups (each with 12 rats): WI-0 minutes (group A), WI-30 minutes (group B), WI-45 minutes (group C), and WI-60 minutes (group D). In each group, the tracheas from 6 rats were imbedded in the greater omentum of 6 other rats. Fourteen days later, the transplanted trachea was obtained from the recipient to evaluate epithelial thickness and regeneration. Six tracheas were obtained from living donors as a control group. Results: There were no significant differences in tracheal transplantation time (mean, 17.66 ± 1.21 minutes). There were no significant differences in epithelial thickness and regeneration between the controls and groups A, B, and C (P < .05). Group D showed no normal epithelial structure of the trachea only with monolayer cells. Conclusions: The time limits of tolerance to WI of tracheal grafts from NHBDs may be 45 minutes.

Effect of Methylene Blue on the Hemodynamic Instability Resulting From Liver Ischemia and Reperfusion in Rabbits

2011-12-01

Abstract: The experimental investigation was performed to study the effects of methylene blue (MB) on hemodynamic, biochemical, and tissue changes among rabbits undergoing liver ischemia and reperfusion (IR). Twenty-four rabbits were randomized into 5 groups: 1, SHAM, control; 2, MB infusion bolus (3 mg/kg); 3, IR, hepatic ischemia for 60 minutes followed by 120 minutes of reperfusion; 4, MB-R, undergoing ischemia that had received an MB bolus infusion (3 mg/kg) prior to reperfusion; 5, R-MB, undergoing ischemia and MB bolus infusion after hemodynamic instability caused by reperfusion. The analysis included continuous recording of vital signs. Blood samples were collected at 0, 60, and 180 minutes of IR to determine blood gases as well as biochemical markers of liver function, nitric oxide, lipid peroxidation, and neutrophil activity. At the end of each experiment, liver tissue samples were collected for histological evaluation of parenchymae markers. Statistical analysis used two-way analysis of variance (ANOVA) tests with significance set at P < .05. Vital signs significantly improved with MB infusion, irrespective of whether it was applied before or after reperfusion. Blood gas data revealed different patterns among the SHAM, MB, IR, MB-R, and R-MB groups, without statistical significance, except for favorable lactate results in the R-MB group (P < .01), which displayed greater survival. Biochemical tests did not show significant differences among the groups, whereas histological analysis revealed favorable appearances for the MB-R and R-MB groups. The MB effect lasted long after reperfusion, suggesting that improvement in the hemodynamic parameters was not based on liver integrity, but rather was possibly related to endothelial function.

Impact of Pre-Existing Left Ventricular Dysfunction on Kidney Transplantation Outcomes: Implications for Patient Selection

2011-12-01

Abstract: Background: End-stage kidney disease patients with decreased left ventricular ejection fraction (EF) are often denied kidney transplantation (KT) for fear of poor graft and patient survival. Methods: We retrospectively studied all patients who underwent KT at our center between 2001 and 2005 to determine the impact of low EF on outcomes post KT. Low EF was defined as <50% EF by noninvasive cardiac imaging. Follow-up was for 1 year post KT. Outcomes assessed included hospitalization for congestive heart failure (CHF), cardiac events, and renal allograft and patient survival. Results: Among 254 patients, 37 had low EF (study group) and 217 had normal EF (≥50%; control group). Post KT, the low EF group had a significantly higher rate of hospitalization for CHF. No significant difference was noted in the rate of cardiac events, graft loss, GFR, and all cause death at 12 months post KT. Conclusion: Patients with low EF should not be excluded from transplantation, given favorable outcomes.

Better Actual 10-Year Renal Transplant Outcomes of 80% Reduced Cyclosporine Exposure With Sirolimus Base Therapy Compared With Full Cyclosporine Exposure Without or With Concomittant Sirolimus Treatment

J. Pliszczynski, B.D. Kahan — 2011-12-01

Abstract: Objective: Retrospective analysis of 10-year outcomes of sirolimus (SRL) plus varying exposure to cyclosporine (CsA) in combination therapy for renal transplantation. Methods: Univariate, multivariate, and receiver operating characteristic (ROC) analyses of 10-year outcomes of 167 subjects treated with full exposures to CsA/SRL/steroid versus 233 with CsA/no SRL/steroid who were generally enrolled in randomized trials versus 192 patients prescribed 80% reduced CsA exposure adjunctive to SRL baseline therapy with steroid withdrawal (groups 1, 2, and 3, respectively). Results: Groups 1 and 3 showed greater 1-year graft survivals (GS) than group 2 (93% and 94% vs 86%; P = .05, particularly when mean SRL C0 ≥ 10.5; P = .02); fewer acute rejection episodes (11% and 19% vs 40%; P < .001) and more frequent success of steroid withdrawal (47% and 66% vs 27%; P < .0001). Group 3 versus 1 displayed a higher mean glomerular filtration rate using the Modification of Diet in Renal Disease (MDRD) formula: 56 versus 49 (P = .02) and 53 versus 41 mL/min per 1.73 m2 (P < .001) at 5 and 10 years, respectively. The 10-year GS among group 1 subjects was predicted by a ≥59 mL/min per 1.73m2 at 1 year using ROC. Multivariate analysis showed factors predictive of 10-year GS among group 1 to include living donor source (P = .004), younger recipient age (P = .02), and fewer HLA-mismatches (P = .02). For group 3, the adverse factors were lower MDRD (P = .01); hypercholesterolemia (P = .01), and advanced donor age (P = .02). Group 3 versus 1 subjects displayed fewer skin tumors (2.6% vs 7.1%; P = .04), sepsis bouts (3.6% vs 9%; P = .04), and herpes virus infection (10% vs. 23%; P = .002), but more urinary tract infections (64% vs 53%; P = .04) and wound problems (43.7% vs 25.1%; P < .0001). Conclusion: An 80% reduction of de novo CsA exposure in combination with SRL engendered improved renal function as well as better graft survival at 10 years compared with patients treated with full CsA exposures with or without SRL co-therapy.

Sequential Monitoring of TIM-3 Gene Expression in Peripheral Blood for Diagnostic and Prognostic Evaluation of Acute Rejection in Renal Graft Recipients

Y. Luo, B. Shi, Y. Qian, H. Bai, J. Chang — 2011-12-01

Abstract: Background: TIM-3 is expressed on primary T effector cells, including th1, ctl, and Th17, which play essential roles in acute allograft rejection (AR). In this study we monitored sequential changes of TIM-3 gene expression among peripheral blood leukocytes (PBL) from renal transplant recipients. Methods: The study consisted of an AR group (n = 24), a no AR group (n = 20), and a stable group (n = 18). Prospective serial blood samples were collected after allotransplantation and during AR episodes. The mRNA encoding for TIM-3 was quantified using real-time reverse-transcription polymerase chain reaction (RT-PCR). Statistical analyses were performed to correlate gene transcript measurements with clinical events. Results: TIM-3 mRNA in PBL showed significantly higher expression in the AR compared with the no AR and stable groups: 286.72 ± 86.28 vs 126.10 ± 28.31 vs 96.91 ± 17.88, respectively (P = .00). The receiver operating characteristic curve showed a specificity of 100% and a sensitivity of 87.5% for the utility of TIM-3 for rejection diagnosis. Antirejection therapy decreased TIM-3 mRNA expression in all AR patients. There was a positive correlation between TIM-3 mRNA expression and serum creatinine (r2 = 0.716; P = .00). Conclusions: TIM-3 mRNA quantification by RT-PCR in PBL may be a promising tool for a noninvasive diagnosis of AR. But the utility for predicting the prognosis of AR after antirejection treatment was limited, owing to the great variations of TIM-3 mRNA expression during AR episodes.

Lymphocyte ATP Immune Cell Function Assay in Pediatric Renal Transplants: Is It Useful?

S. Vyas, I. Roberti — 2011-12-01

Abstract: The ultimate goal for an allograft is a balanced immunosuppression to provide the longest graft survival with minimal side effects. In this retrospective study, we correlate the immunosuppresion level as determined using the Cylex assay (Immu know, Columbia, MD) with clinical events. Demographic data such as age at the time of transplant, gender, ethnicity, time posttransplantation, tacrolimus level, and induction therapy were correlated with Cylex levels. Cylex from children with an infection or acute rejection were compared to those from stable patients. All children received induction with basiliximab or thymoglobulin followed by a standard regimen with tacrolimus, steroids, and mycophenolate mofetil. Fifty-nine Cylex results were obtained in 44 pediatric renal transplant recipients. Cylex values ranged from 20 ng/mL to 728 ng/mL. We did not find significant correlation between any of the demographic characteristics studied (tacrolimus level, induction therapy, acute rejection, and cylex levels). Fifteen patients had severe infections requiring hospitalization: 11 of 15 (73%) had Cylex < 130 ng/mL; these levels differed significantly from those obtained in patients without infections. We concluded that clinical utility of Cylex is limited in children with kidney transplants because it did noes correlate with the prescribed dosage of medications or with rejection. However, low Cylex levels were highly correlated with serious infections.

The Utility of Cytodiagnostic Urinalysis as a Tool to Diagnose Kidney Allograft Dysfunction in the Era Lymphocyte-Depleting Induction Therapy

2011-12-01

Abstract: Cytodiagnostic urinalysis (CDU) has been used to evaluate causes of kidney allograft dysfunction, such as an acute rejection episode (ARE), calcineurin inhibitor (CNI) toxicity, or polyoma virus infection. We examined the concordance between CDU and allograft biopsy in patients with allograft dysfunction. Between 2002 and 2006, 201 patients had CDU performed within 7 days of a biopsy. The cohort was black (73%) with, male preponderance (59.2%), and an overall mean age of 48 ± 13 years with 46% having received a deceased donor kidney. The induction regimen consisted of either antithymocyte globulin or alemtuzumab. CDU results that demonstrated 5 to 10 lymphocytes per high-power field (HPF) and >20 lymphocytes/HPF had 2.5 increased odds of predicting acute rejection (AR) on biopsy (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.12–5.79; P = .025). In the era of antithymocyte globulin induction, a CDU result demonstrating >5 lymphocytes/HPF had a 4.3 increased odds of predicting AR (CI 1.76–10.50; P = .001). This association was lost with alemtuzumab induction. A positive CDU result for calcineurin inhibitor (CNI) toxicity did not predict CNI nephrotoxcity on biopsy, but a positive CDU for polyoma virus infection predicted polyoma virus nephropathy (OR 22.18; CI: 4.41–111.63; P < .001). In conclusion, CDU is an adjunctive diagnostic tool for kidney transplantation.

Outcome of Kidney Transplantation From Elderly Donors After Cardiac Death

S.R. Thornton, N. Hamilton, D. Evans, T. Fleming, E. Clarke, J. Morgan, N. Kadi — 2011-12-01

Abstract: Background: The rate of renal transplantation is limited by the number of donor organs available. A valuable source of organs is currently supplied by donation after cardiac death (DCD). At the Richard Bright Renal Unit, we have expanded our criteria for DCD, increasing the upper age limit for donation from 65 to 70. Method: We performed a retrospective analysis of all DCD recipients between 2003 and 2009. We compared outcomes for patients age <60 versus >60 as measured by delayed graft function and estimated glomerular filtration rate (eGFR) and incidence of graft failure. Results: One hundred thirty-six DCD transplantations took place. Our early data showed excellent results for non–heart-beating donation. Over the last 7 years, the average age of DCD donors has increased from 43 in 2003 to 50 in 2009. The increase in age has been correlated with a decrease in average recipient eGFR from 59 in 2003 to 32 in 2009. Recipients of kidneys from older DCD donors (>60) have significantly lower eGFRs at 1 month and 1 year compared to kidneys from donors aged <60. The incidence of delayed graft function in recipients of kidneys from donors aged >60 was 71% compared to 40% for <60 age group. Despite this, we have not found any evidence of higher graft failure rates in the recipients of grafts from the >60 donor age group. Conclusions: Expanding the age limits of our DCD donor program has led to an increased average donor age, reduced average eGFR, and increased delayed graft function. There is no evidence of reduced graft survival.

Factors of Impact on Graft Function at 2 Years After Transplantation in Living-Donor Kidney Transplantation: A Single-Center Study in China

J. Zhao, W.L. Song, C.B. Mo, Z.P. Wang, Y.X. Fu, G. Feng, J.M. Zheng, Z.Y. Shen — 2011-12-01

Abstract: Objective: The aim was to investigate the factors that affect graft function at 2 years after transplantation in living related–donor kidney transplantation. Methods: We retrospectively reviewed the clinical data of 144 patients who underwent living related–donor kidney transplantation in our hospital from December 2005 to December 2008. Recipients were divided into 2 groups according to glomerular filtration rate (GFR) at 2 years after transplantation: ≤60 mL/min/1.73 m2 (n = 51) and >60 mL/min/1.73 m2 (n = 93). Variables which affected graft function were compared between the groups. The significant factors were analyzed using logistic regression. Results: Univariate analysis showed significant differences for donor age, donor GFR, recipient weight, recipient body mass index, donor-to-recipient body weight ratio, and acute rejection episodes (P < .05). Logistic regression analysis revealed the independent factors affecting renal function at 2 years after transplantation to be donor GFR (β = 0.032; odds ratio [OR] 1.032; P = .004) and recipient body weight (β = −0.069; OR 0.934; P = .001). Receiver operating characteristic (ROC) curve analysis showed cutoff values of donor GFR and recipient body weight to be >111.25 mL/min/1.73 m2, and ≤67 kg, respectively. Areas under the ROC curve of donor GFR and recipient body weight were 0.612 and 0.665, respectively. Sensitivity and specificity of donor GFR were 43.0% and 78.4%, respectively. Sensitivity and specificity of recipient body weight were 82.8% and 45.1%, respectively. Conclusions: Donor GFR and recipient body weight were the independent factors effecting renal function at 2 years after transplantation.

Changes of Progesterone-Induced Blocking Factor in Patients After Kidney Transplantation

2011-12-01

Abstract: The prediction of graft rejection can play an important part in graft survival. Analysis of immune reactions has shown that graft rejection shares mechanisms with recurrent abortions during pregnancy. Progesterone-induced blocking factor (PIBF), a mediator of progesterone that blocks natural killer cell activity in peripheral blood, produces antiabortive effects. The aim of this study was to examine the PIBF concentration in the urine of transplanted recipients. The study included 116 white adults (70 men and 46 women) of median age 49.3 years, who had undergone kidney transplantations. The median duration after transplantation was 3.46 years. The average period between renal disease and our measurement was 12.3 years, and the median interval between graft rejection and our study was 1.75 years. Urine samples were used to measure PIBF concentrations by an enzyme-linked immunsorbent assay. PIBF urinary concentrations decreased significantly in patients who experienced ≥1 rejection episode (31.8 ± 2.2 ng/mL) compared with those without any episode (22.7 ± 1.2 ng/ml; P < .01). Moreover, the urinary PIBF level was significantly lower among patients who had increased creatinine and urea nitrogen levels in blood samples (P < .05 and P < .01, respectively). Decreased PIBF values in kidney transplant patients followed previous rejection episodes. A close negative correlation was observed between urinary PIBF concentrations and blood levels of creatinine and urea nitrogen. These findings suggested that PIBF detection may predict graft rejection in transplant recipients.

Efficacy and Safety of Changing From Cyclosporine C0 to C2 Monitoring in Stable Recipients Following Renal Transplantation: A Prospective Cohort Study

Y. Zhang, X.D. Zhang, Y. Wang — 2011-12-01

Abstract: Cyclosporine doses can be adjusted individually to decrease the occurrence of rejection and nephrotoxic episodes using concentrations at 2 hours postdosing (C2). However, some transplantation centers still use tough concentrations (C0) to adjust cyclosporine doses among stable renal transplant recipients. We analyzed the efficacy and safety of changing from monitoring C0 to C2 among stable recipients following living relative donor renal transplantation. We enrolled 65 stable renal transplant recipients whose cyclosporine (Neoral) dosages were adjusted by C0, recording their cyclosporine C2 values. They were divided into low (<500 ng/mL, n = 25), target (500–600 ng/mL, n = 23), or high (>600 ng/mL, n = 17) C2 groups. The cyclosporine dose was prospectively modified in the low and high C2 groups; all patients were followed for 12 months. We compared the incidences of complications among their transplanted kidneys and other organs. Among patients in the high C2 group, the C2 target value was achieved by reducing the cyclosporine dose by up to 575.0 mg (mean = 33.8 mg/patient); 88.2% of patients showed stable levels of creatinine (Cr) and urea nitrogen (BUN) during the follow-up with decreased blood cholesterol and uric acid levels in some patients, while two subjects suffered acute rejection episodes. Among the low C2 group, the target value was achieved by increasing the cyclosporine dose by up to 755.0 mg (mean = 30.2 mg/patient); during the follow-up with 84.0% of subjects displaying stable levels of Cr and BUN, four suffered increasing Cr and BUN values. Although most of stable recipients in this study benefited from C2 monitoring, some patients suffered rejection or nephrotoxicity episodes. One must be cautious to change from monitoring C0 to C2 in stable recipients following renal transplantation.

Impact of the Conversion of the Immunosuppressive Regimen from Prograf to Advagraf or to Sirolimus in Long-term Stable Liver Transplant Recipients: Indications, Safety, and Outcome

A. Perrakis, K. Schwarz, S. Yedibela, R.S. Croner, W. Hohenberger, V. Müller — 2011-12-01

Abstract: Background: Compliance problems have arisen due to the twice a day administration of calcineurin inhibitors (CNI). We examined the safety, indications, and efficacy in terms of graft and patient survivals after conversion from tacrolimus to Sirolimus or Advagraf. Patients and Methods: Between January 2006 and December 2009, 36 orthotopic liver transplantation patients underwent conversion of the immunosuppressive regimen from Prograf to either Sirolimus (group 1; n = 10) or Advagraf (group 2; n = 26). A group of patients taking Prograf was used as a control group (group 3; n = 15). We identified 51 patients of mean age 57 years and male:female percentages of 57%:43% from a prospective database. Renal and liver graft functions, patient survival, as well as laboratory and clinical data over at least 12 months (mean, 38) were the investigated parameters. Results: Patients converted to Sirolimus did not show significantly improved renal function at 12 months as evidenced by creatinine levels (1.31 mg/dL +/− 0.47 vs 1.34 mg/dL +/− 0.78) and glomerular filtration rate (GFR, 57+/− 16 vs 56+/− 16 mL/min). However, there were significant antiproliferative effects. Patients with a hepatocellular carcinoma in the pretransplantation phase remained without a recurrence. The side effects including ankle edema, aphthae, and tachyarrhythmia absoluta, required reconversion to the CNI. Patients prescribed Advagraf reported a better life quality because of the single administration and a slight, insignificant improvement in renal function. An acute rejection episode was evidenced under either immunosuppresant. Conclusion: Sirolimus is a safe immunosuppressive option in liver transplant recipients suffering from hepatocellular carcinoma. Advagraf showed a lower incidence of side effects than Prograf and probably is not as harmful for renal function, offering better compliance and better life quality.

Tacrolimus Pharmacokinetics in Hispanic Children After Kidney Transplantation

G. Cherala, M.Y. Munar, A. Naher, A. Al-Uzri — 2011-12-01

Abstract: Ethnic differences in drug pharmacokinetics are well recognized including that for tacrolimus (TAC) in adult subjects. However, similar knowledge among pediatric populations is missing. Our limited retrospective study compares steady-state pharmacokinetics of TAC in Hispanic versus non-Hispanic children. Serial blood samples were collected and whole blood concentrations of TAC were measured using radioimmunoassay. Compared with non-Hispanic children, Hispanic children had lower measures of drug exposure (maximum drug concentration [Cmax] and area under the drug concentration-time curve [AUC0-∞]), higher volume of distribution, and faster clearance. Interestingly, only in Hispanic children, significant correlations were found between body weight and clearance, age and volume of distribution, and Schwartz estimated glomerular filtration rate and half-life. In conclusion, our study suggests that ethnic differences exist between Hispanic and non-Hispanic children in TAC PK, and based on our preliminary findings, either a higher or more frequent TAC dosing may be required for effective immunosuppression therapy in Hispanic children.

Preemptive Kidney Transplantation in Systemic Lupus Erythematosus

A. Naveed, C. Nilubol, J.K. Melancon, R. Girlanda, L. Johnson, B. Javaid — 2011-12-01

Abstract: Preemptive kidney transplantation is associated with superior outcomes. Patients who have kidney failure due to systemic lupus erythematosus (SLE) may not receive a preemptive kidney transplant because of the concern for risk of disease recurrence with shortened graft and patient survival. We identified 8001 patients in the United Network for Organ Sharing dataset who underwent kidney transplantation between October 1987 and February 2009 with kidney failure due to SLE. Seven hundred thirty patients received a preemptive kidney transplant with 7271 patients who were on dialysis before transplantation; their mean ages were 40.0 ± 11.6 years and 36.9 ± 11.7 years, respectively, (P < .01). Women constituted 82.5% of preemptive and 81.4% of non-preemptive groups (P = .47). Preemptive transplant recipients were more likely to receive a living donor kidney transplant (odds ratio [OR] = 3.6; 95% confidence interval [CI] = 3.3–4.5; P < .01). In unadjusted analyses, preemptive transplantation was associated with lower risk of recipient death (hazard ratio [HR] = 0.52; 95% CI = 0.38–0.70; P < .01). The difference remained significant after adjustment fr covariates (HR = 0.55; 95% CI = 0.36–0.84; P < .01). Graft survival was also superior among preemptive kidney transplant recipients in both unadjusted (HR = 0.56; 95% CI = 0.49–0.68; P < .01), and adjustment analyses (HR = 0.69; 95% CI = 0.55–0.86; P < .01). We concluded that preemptive kidney transplantation among patients with SLE was associated with superior patient and graft outcomes and should be considered when feasible.

Opportunistic Posttransplantation Virus Infections in Renal Transplant Recipients

J.H. Hu, H. Zhao, Y.P. Huang, X. Zhang, H.N. Gao, M.F. Yang, J. Fan, W.H. Ma — 2011-12-01

Abstract: Background: Opportunistic virus infection is one of the most common complications in renal transplant (RT) recipients. Cytomegalovirus (CMV) and BK virus (BKV) are important pathogens and each of these infections affects the other. In contrast, there is only limited information on JC virus (JCV) infection and its relation to CMV infection in RT recipients. This prospective study investigated the rates of JCV and CMV infections and their risk factors and correlations. Methods: We studied 52 RT recipients. JCV and CMV were detected using nested qualitative polymerase chain reaction assays of urine. The clinical characteristics of JCV and CMV infection were compared and risk factors analyzed with the use of binary logistic regression. Results: JCV and CMV were detected in 40.4% and 34.6% of the RT recipients, respectively. Cyclosporine (CsA) was a risk factor for both JCV and CMV infection (odds ratio [OR] 7.187; P = .002; OR 4.182; P = .021); CMV infection was a risk factor for JCV infection (OR 3.900; P = .039). Conclusions: JCV and CMV infections are common in RT recipients. CsA is a risk factor for both JCV and CMV infection. JCV infection is related to CMV infection.

The Seroprevalence of Helicobacter pylori Infection in Renal Transplant Recipients

Z.R. Khameneh, N. Sepehrvand, S. Hatami, A.T. Afshari — 2011-12-01

Abstract: Background: Helicobacter pylori (HP), a small gram-negative spiral bacillus living in the mucus layer of the human stomach, mediates some gastrointestinal disorders. Considering the immunocompromised nature of transplant recipients due to immunosuppression, they are generally prone to viral and bacterial infectious diseases. In this study we sought to investigate the seroprevalence of HP infection among Iranian kidney transplant recipients. Methods: We selected randomly 91 kidney transplant patients who were examined for anti- HP Immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay method (Lake Success, NY, USA). Results: Forty-three subjects (47.3%) were seropositive for anti-HEV IgG. There was no difference by age (P = .49), sex (P = .22), blood transfusion history (P = .19), or hemodialysis history (P = .46) between seropositive and seronegative groups, but there was a significant difference regarding the educational status of the subjects (P = .03), The difference was not confirmed by considering diploma as the cut point to categorize subjects (P > .05). Comparing age groups, Pearson chi-square analysis revealed no significant correlation between HP seropositivity and increasing age (P = .963), even when controlled for sex, educational status, history of blood transfusion, or hemodialysis. Conclusion: The frequency of transplant recipients with anti-HP IgG antibodies in our institution (47.3%) was not higher than that in the general population (almost 60% in Urmia). This rate was lower than reports from developing countries possibly due to better health and sanitation.

Impact of Vitamin D on Proteinuria, Insulin Resistance, and Cardiovascular Parameters in Kidney Transplant Recipients

D.R. Lee, J.M. Kong, K.I. Cho, L. Chan — 2011-12-01

Abstract: Low vitamin D levels prevalent in patients with chronic kidney disease have been reported to be associated with proteinuria, insulin resistance, and cardiovascular disease. Kidney transplant recipients are also susceptible to low vitamin D levels but their clinical significance is uncertain. This study investigated the prevalence and association of vitamin D insufficiency with proteinuria, insulin resistance, and cardiovascular parameters among 95 living donor kidney transplant recipients. Levels of 25-hydroxyvitamin D [25(OH)D] were stratified into an insufficient group [25(OH)D ≤ 30 ng/mL; n = 19] versus a normal group [25(OH)D > 30 ng/mL; n = 76]. Proteinuria (urinary protein-creatinine [P/C] ≥ 0.2 mg/mg), insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) and cardiovascular parameters were compared between groups. Twenty percent of subjects showed vitamin D insufficiency. Proteinuria was higher among the vitamin D insufficient than the normal group (47.4% vs 18.7%; P = .02). 25(OH)D levels inversely correlated with urinary P/C ratio and intact parathyroid hormone (I-PTH) levels (r = −.24, P = .02 and r = −.23, P = .02, respectively). No correlations were observed between 25(OH)D levels and HOMA-IR scores or cardiovascular parameters. On univariate analysis, proteinuria and i-PTH levels were independent predictors of vitamin D insufficiency (P < .01 and P = .03, respectively). Multivariate analysis demonstrated proteinuria to be a significant predictor of vitamin D insufficiency (odds ratio = 4.526; P = .03). In conclusion, vitamin D insufficiency was common and significantly associated with proteinuria among kidney transplant recipients. Additional studies are needed to clarify the causal relationship of vitamin D insufficiency with proteinuria and to determine the role of vitamin D supplementation to attenuate the development of proteinuria.

Lipid Profile Changes During the First Year After Kidney Transplantation: Risk Factors and Influence of the Immunosuppressive Drug Regimen

2011-12-01

Abstract: Aim: This study analyzed the incidence, time course, and risk factors associated with dyslipidemia during the first year after kidney transplantation among patients receiving various immunosuppressive regimens. Methods: The analysis included 474 kidney transplant recipients receiving cyclosporine (CSA) combined with sirolimus (SRL; n = 137) or mycophenolate (MMF, n = 58) or everolimus (EVR, n = 47); or SRL combined with MMF (n = 32); or tacrolimus (TAC) combined with SRL (n = 86) or MMF (n = 114). All patients received prednisone. We evaluated the influence of demographic features, clinical outcomes, and statin use on lipid profiles during the first year after transplantation. total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (hdl-C), low-density lipoprotein cholesterol (ldl-C), non-HDL-C, TC:HDL-C, LDL-C:HDL-C, TG:HDL-C. Results: Lipid profiles were within the recommended ranges in 28% of patients pretransplantation and in 10% at 1 year; 27% of them received statins. At 1 year, LDL-C <100 mg/dL was observed in 31.8% of patients but more than 35% of these patients still showed other lipid fractions or ratios outside recommended target concentrations. Among all patients with LDL-C > 100 mg/dL, almost 70% to 80% had other lipid fractions or ratios within target ranges. A logistic regression analysis showed age, gender, time on dialysis, diabetes, type of calcineurin inhibitor (CSA vs TAC), adjunctive therapy (SRL/EVR vs MMF) and prednisone dose to be associated with dyslipidemia. Conclusion: Dyslipidemia is frequent at 1 year after transplantation. The lack of agreement among changes observed in lipid fractions and ratios suggests that more studies are necessary to guide therapy besides targeting LDL-C concentrations as recommended by current guidelines.

Urinary Metabolomics in Monitoring Acute Tubular Injury of Renal Allografts: A Preliminary Report

J. Wang, Y. Zhou, M. Xu, R. Rong, Y. Guo, T. Zhu — 2011-12-01

Abstract: Acute tubular injury (ATI) is very common in biopsy specimens from renal allografts that suffer from delayed graft function (DGF) or dysfunction. Currently there are few reports on investigating small molecule metabolites in urine samples from transplant recipients as a noninvasive method to predict the ATI of renal allografts instead of an allograft biopsy. In our study matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS) was used to analyze small molecule metabolites in urine samples from renal transplant recipients with biopsy-proven slight ATI or moderate ATI or acute tubular necrosis (ATN). To evaluate the ATI-specific value of those small molecules, we applied the Principal Component Analysis (PCA) program. Mass spectra data were imported into the PCA, where loading graphs were constructed to express the constituents of the urine samples. Slight ATI, moderate ATI, or ATN of renal allografts were separated obviously in the loading graph. The position of urine samples in the graph may reflect the tubular injury status of allografts. A farther apart point from the original site may mean the allograft suffered from more severe ATI (even ATN), and vice versa. Detection of small molecule metabolites in urine samples of recipients through MALDI-FTMS may offer a promising noninvasive, high throughput, rapid tool to predict ATI/ATN of renal allografts.

Patterns of IgG Subclass Deposits in Membranous Glomerulonephritis in Renal Allografts

N. Kearney, J. Podolak, L. Matsumura, D. Houghton, M. Troxell — 2011-12-01

Abstract: Background: Membranous glomerulonephritis (MGN) may develop in the renal allograft either de novo or as a recurrence. These 2 forms of MGN may have different pathogenic mechanisms, with different IgG subclass profiles in the immune deposits. This study examined IgG subclass distributions in recurrent and de novo MGN in allograft kidneys. Methods: We identified allograft kidneys with MGN, including 7 with recurrent MGN, 2 with de novo MGN, and 2 atypical/indeterminate, and determined the relative intensity of IgG1, IgG2, IgG3, and IgG4 staining in capillary wall deposits by immunofluorescence microscopy. Results: IgG4 was the dominant or codominant IgG subclass in capillary loop deposits in all 7 cases of recurrent MGN. IgG1 staining was dominant in 3 of 4 de novo or atypical MGN cases and codominant with IgG4 in the fourth. Conclusions: Although pretransplantation kidney biopsies were not available for comparisons, these findings suggest that all allograft recurrences represent idiopathic MGN and that de novo MGN cases had a different pathogenic mechanism.

Routine Short-Term Ureteral Stent in Living Donor Renal Transplantation: Introduction of a Simple Stent Removal Technique Without Using Anesthesia and Cystoscope

J. Dong, J. Lu, Q. Zu, S. Yang, S. Sun, W. Cai, L. Zhang, X. Zhang — 2011-12-01

Abstract: Objective: We evaluated routine short-time insertion of ureteral stent in living donor renal transplant at a single center. It was easy to remove the stent without cystoscopy and anesthesia. Materials and methods: Between October 2007 and July 2010, a single surgeon performed 76 living donor renal transplantations at one institute. All recipients underwent extravesical ureteroneocystostomy with a 2-0 silk suture passed through the venting side hole of the double-J stent into the bladder; a quadruple knot prevented the suture's slippage or distraction from the stent. After removal of the indwelling catheter at 5 days posttransplantation, the 2-0 silk passed with the urinary stream within 72 hours. The double-J stent was removed at 7 to 10 (mean 8.4) days after kidney transplantation by pulling the 2-0 silk out of the urethral orifice without anesthesia or cystoscopy. Results: There was only one case of stenosis, which was resolved by surgery. No patient developed urinary leakage. There were three episodes of urinary tract infection in 70 patients during first 6 months' follow-up. Conclusions: Routine short-term stenting is a safe and effective technique in living donor renal transplantation. Removal of the stent is feasible without cystoscopy or anesthesia.

Association Between Urothelial Carcinoma After Kidney Transplantation and Aristolochic Acid Exposure: The Potential Role of Aristolochic Acid in HRas and TP53 Gene Mutations

2011-12-01

Abstract: Objective: We sought to investigate the association between urothelial carcinoma (UC) after kidney transplantation and aristolochic acid (AA) exposure, and to explore the potential role of AA in HRas and TP53 gene mutations. Materials and Methods: UC was confirmed in 100 of 3790 patients who underwent kidney transplantation between January 1974 and May 2011. We retrospectively analyzed clinical data for these patients. Malignancies were identified in 136 patients (15 males and 85 females, of age range 27–71 years mean, 53.2 ± 6.3). UC was the most common diagnosis (100/136; 73.5%). The median time from transplantation to the first confirmed diagnosis of a tumor was 34.5 months (range, 2–273). Polymerase chain reaction–based resequencing methods were used to detect mutations in the target regions of exons 2 and 3 of the HRas gene and exons 5, 6, 7, and 8 of the TP53 gene in 90 of 100 samples. Results: UC was identified in 53 of 380 patients exposed to AA and 47 of 3410 patients not exposed to AA (P < 0.05). Pathologic examination of the UC specimens from AA-exposed patients identified heterozygous HRas changes in 3 cases, and deletion or replacement mutations in the TP53 gene in 4. No genetic mutations were observed among the control group. Conclusion: UC after kidney transplantation significantly correlated with AA exposure; however, there seemed to be no significant difference in mutations in exons 2 and 3 of the HRas gene and those in exons 5, 6, 7, and 8 of the TP53 gene in terms of tumor development, a result that is inconsistent with previous studies.

Does Ultrasonic Energy for Surgical Dissection Reduce the Incidence of Renal Transplant Lymphocele?

E.W. Nelson, M.E. Gross, M.C. Mone, H.J. Hansen, X. Sheng, K.M. Cannon, S. Alder — 2011-12-01

Abstract: Objective: To determine the difference in post–renal transplant lymphocele rate based on the surgical dissection technique for control of lymphatics by examining the historical case group under the direction of a single, university-based surgeon in a retrospective, cohort study. Patients: Five hundred thirty-two consecutive renal transplant patients from January 1994 to December 2009. Findings: Of the 532 cases studied, 259 (48.7%) had suture ligation and 273 (51.3%) employed ultrasonic dissection (UD) for control of lymphatics during renal transplantation. There was no difference found in the rate of lymphocele formation, requiring either percutaneous or surgical drainage, when surgical ties (8.9%) were compared to UD (9.2%; P = .999). Logistic regression analysis showed that the odds ratio for developing a lymphocele was independent of surgical dissection technique. Within the logistic analysis, the prediction for lymphocele was increased 3.29 times for pediatric patients (P = .002) and increased 2.97 times for those who received a living donor graft (P = .001), and there was a trend for those with a history of more than one renal transplant of 2.01 times (P = .079). Summary: Surgical dissection technique was not a factor in the development of post–renal transplant lymphocele. Younger age, living donor transplant, and repeat transplant status were found to be predictive variables for symptomatic lymphoceles requiring drainage, which may be considered when patients present for posttransplant evaluations for laboratory alterations.

Skin Cancer Following Kidney Transplantation: A Single-Center Experience

M. Karczewski, M. Stronka, J. Karczewski, K. Wiktorowicz — 2011-12-01

Abstract: One of the major problems associated with prolonged immunosuppression is a high occurrence of skin malignancies among kidney recipients. Studies have shown that nonmelanoma skin cancer is the most frequently occurring tumor after organ transplantation. The aim of this study was to determine the incidence of and identify possible risk factors for skin malignancies among a population of kidney recipients. This retrospective, single-center cohort comprised 1672 patients transplanted from 1994 to 2011. Only patients with a confirmed diagnosis of skin cancer were selected for medical records review. Among 836 kidney transplant recipients remaining under our care since 1994, skin malignancies were diagnosed in 16 patients (1.9%). The histological diagnoses included squamous cell carcinoma (n = 8; 50.0%); basal cell carcinoma (n = 6; 37.5%) or malignant melanoma (n = 2; 12.5%). The slightly lower incidence of skin malignancies noted in our study compared with other reports might result from differences in the length of follow-up. Some patients diagnosed with skin cancer were treated in local dermatology clinics. Also, a lower exposure to the sun characteristic for the latitude and differences in immunosuppressive therapies could be partially responsible for the lower skin cancer incidence. We also did not observe any association between other reported risk factors, such as age, human leukocyte antigen mismatch, duration of pretransplant hemodialysis, particular immunosuppressive therapies and the skin cancer occurrence among our kidney recipients.

Orthotopic Liver Transplantation in Critically Ill Cirrhotic Patients With Multi-Organ Failure: A Single-Center Experience

A. Umgelter, K. Lange, A. Kornberg, P. Büchler, H. Friess, R.M. Schmid — 2011-12-01

Abstract: Due to the lack of donor organs for orthotopic liver transplantation (OLT) in Germany, a larger proportion of patients advance to multi-organ failure (MOF) before OLT. Twenty-three patients on the waiting list for OLT were admitted to our intensive care unit (ICU) from January 2007 until September 2009. They consisted of 16 men and 7 women of median (25th–75th percentile) age of 60 years (54–65). Acute Physiology and Chronic Health Evaluation (APACHE II) score upon ICU admission was 26 (19–34); Model of End-Stage Liver Disease (MELD) score was 29 (22–41); Sequential Organ Failure Assessment (SOFA) score was 12 (8–16). The 90-day mortality rate was 39%. A decrease in MELD score during the first 48 hours (−2 [−5–0] vs 2 [−1–4]; P = .019) was associated with survival. Thirteen patients underwent transplantation from the ICU. By the time of the OLT, the MELD scores had deteriorated to 38 (33–39) and SOFA scores to 19 (18–19). All patients were mechanically ventilated and received hemodynamic support with catecholamines. Ten of 13 patients (77%) received renal replacement therapy and/or single pass albumin dialysis. Eight of 13 patients (62%) had a SOFA score of 3 or 4 (organ failure) in each of the respective subscores for the cardiovascular, renal, and respiratory systems at the time of OLT. The 90-day mortality rate after OLT was 38% and the 1-year-mortality rate was 54%. Patients who did not survive 90 days post OLT showed lower MELD scores on admission (33 [18–35] vs 44 [32–46]; P = .045), an increased MELD during the first 48 hours (3 [1–4] vs −2 [−8–1]; P = .002), and a longer ICU stay before OLT (32 [18–37] vs 8 [2–15]; P = .006). In conclusion, OLT may be successful treatment for cirrhotic patients with MOF. Outcomes of MOF in cirrhotic patients may improve after OLT but are generally worse than acceptable. A shorter ICU waiting time seemed to be beneficial.

Social Determinants of Orthotopic Liver Transplantation Candidacy: Role of Patient-Related Factors

N. Kemmer, A. Alsina, G.W. Neff — 2011-12-01

Abstract: Introduction: Eligibility for orthotopic liver transplantation (OLT) requires careful selection of the best possible candidate. The aim of this study was to identify factors associated with transplantation ineligibility. Method: This was a retrospective cohort study of all patients evaluated for OLT at our center (2004–2006) and deemed not eligible. We identified all patients who were evaluated using information from our transplantation database. We extracted demographic data, insurance status, laboratory data, and clinical information including psychosocial evaluations. Results: During the study period 242 evaluated candidates were not listed for transplantation. The most common reason for ineligibility for transplantation listing was early referral (n = 59; 24.4%), followed by psychosocial (18.6%), medical contraindications (17.3%), death during evaluation (n = 32; 13.2%), malignancy (n = 22; 9.1%), declined evaluation or transfer to other transplantation center (n = 21; 8.7%), and other reasons (8.7%). In contrast to whites, psychosocial factors were the most common reason among African American candidates. Conclusion: This study provides insight into factors contributing to OLT ineligibility among candidates of various ethnic backgrounds.

Right Lobe Living-Donor Liver Transplantation With or Without Middle Hepatic Vein: A Meta-Analysis

S. Zhang, Z. Dong, M. Zhang, Q. Xia, D. Liu, J.J. Zhang — 2011-12-01

Abstract: Objective: The purpose of this meta-analysis was to compare outcomes after right-lobe living-donor liver transplantation (LDLT) with or without the middle hepatic vein (MHV). Methods: Studies were identified through a computerized search of Pubmed, Embase, Ovid, the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials, the Cochrane Library database, and the Web of Science. Two reviewers independently assessed the quality of each study and abstracted outcome data. We extracted data for liver functional recovery in donors, donor hospital stay, donor complications and liver functional recovery in recipients. We synthesized published data using random-effects and fixed-effect models, expressing results as weighted mean differences (WMD) or relative risk (RR). Results: The 11 included eligible studies came from medical centers worldwide. Significant differences between “with MHV” versus “without MHV” groups were not observed for liver functional recovery (P = .08; WMD = −2.88), donor hospital stay (P = .00; WMD = 0.00), or donor complications (P = .90; RR = 1.02). However, our meta-analysis showed a significant benefit for recipients liver functional recovery favoring the MHV group (P = .02; WMD = −33.06). Conclusions: Our meta-analysis discovered that right lobes with MHV not only experienced better liver functional recovery in recipients, but also caused no greater harm or risk to donors.

Orthotopic Liver Transplantation in a Multiethnic Population: Role of Spatial Accessibility

N. Kemmer, A. Alsina, G.W. Neff — 2011-12-01

Abstract: Introduction: Access to orthotopic liver transplantation (OLT) varies among different ethnic groups. The aim of this study was to determine if distance from transplantation center (DT) impedes referral pattern and accessibility to OLT among ethnic groups. Method: This is a retrospective cohort study of all patients evaluated for OLT at our center (2002–2007). The ZipCode Basic software was used to compute distance between the candidate's residence and transplantation center. Results: Five hundred one patients were evaluated during the study period and there were 439 (87.6%) whites 43 (8.6%) African Americans (AA), and others (3.8%). The median DT was 36.8 miles (range, 0.5–231), and there was no significant correlation with the Model for End-Stage Liver Disease (MELD) at presentation (P = .87). Although AA had a higher likelihood of residing closer to a transplantation center they were more likely to have a higher MELD at presentation (20 vs 15.4; P < .001) and less likely to be referred early to initiate OLT evaluation (11.6% vs 26.4%; P = .04). Additionally, type of insurance correlated with higher MELD at presentation. Conclusion: DT was not a contributory factor to the observed access disparity in our patient population, rather the insurance type and disease severity as determined using MELD differed significantly among ethnic groups.

Cost Analysis of Liver Transplantation in Turkey

M. Akarsu, M. Matur, S. Karademir, T. Unek, I. Astarcioglu — 2011-12-01

Abstract: The study sought to determine the costs of liver transplantation in Turkey. All costs except physician charges were retrospectively investigated in the period from hospitalization to discharge. Liver transplantation was performed in 326 patients between 1999 and 2009. After exclusion of patients whose records could not be accessed (n = 5), who underwent second transplantations in the same hospitalization (n = 3) or who died before discharge (n = 39), 279 patients were eligible for the study. The mean cost of liver transplantation was 30.823 dollars. The mean cost in 2008 was significantly higher than for all other years; thereafter it decreased. Costs were shown to be higher among patients with model for end-stage liver disease (MELD) scores >15. Although there was no significant cost difference among United Network for Organ Sharing (UNOS) groups, the mean costs of subjects of the B group were significantly lower than those of the Child C subjects C (P = .01). When we evaluated the relationship between etiological groups and costs the highest expenses were noted among hepatitis B virus (HBV) and hepato cellular carcinoma (HCC) patients with 75% HBV-positivity together. There was no significant difference between age, gender, and body mass index (BMI) of recipients. The costs did not significantly change with the presence of diabetes mellitus (DM) or portal vein thrombosis before transplantation or antibiotic use after transplantation. Although there was no difference between donor age and costs, living donor transplantation showed significantly higher costs than cadaveric donor cases (P = .01). In conclusion, liver transplantation is an effective treatment in end-stage liver diseases with high cost, albeit in Turkey it is relatively lower than other countries.

Donor Age Does Not Influence 12-Month Outcome After Orthotopic Liver Transplantation

2011-12-01

Abstract: Objective: Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease to date. The discrepancy between the numbers of donor livers and recipients has become a significant problem, resulting in a high patient mortality on the waiting list. Due to this, an expansion of the donor pool is necessary, for example, by accepting donor grafts from elderly donors. The aim of this study was to investigate the outcome after OLT depending on donor age. Methods: We retrospectively evaluated the outcome of 272 full-size cadaveric initial single OLTs within 12 months after OLT. The outcome was analyzed by dividing the collective into four donor age categories: donor age under 50, between 50 and 59, between 60 and 69, and 70 years or above. The outcome after OLT in these patients was retrospectively reviewed by using a prospective database. Patients positive for hepatitis C were excluded from the analysis. Results: No increase of initial nonfunction was observed. Furthermore, no significant differences with regard to surgical complications and serum liver parameter were observed between the groups. Neither patient mortality rates nor rejection rates were different between the groups. However, ischemic-type biliary lesion rates increased significantly with donor age over 70 years (P < .05). Conclusions: The acceptance of liver grafts from older donors is a possible alternative to narrow the gap between donated and required organs. Safe use under optimal protocols is necessary to avoid a deterioration of post-OLT results.

International Collaboration of Turkey in Liver Transplantation Research: A Bibliometric Analysis

K. Bas, M. Dayangac, O. Yaprak, Y. Yuzer, Y. Tokat — 2011-11-14

Abstract: Objectives: Scientific publications are valuable markers of scientific activity for countries. We performed a bibliometric study to evaluate the number of publications written by Turkish authors. The aim of this study is to evaluate Turkey's contribution in terms of number of publications included in Science Citation Index Expanded (SCI-E) in the scientific field of liver transplantation compared with other countries. To our knowledge, this is the first bibliometric study in liver transplantation research of Turkey. Materials and methods: ISI Web of Knowledge-Science was used for the analysis. All scientific works published included in SCI-E in English from 1980 to August 10, 2011, were analyzed. A retrospective search was performed using key words “liver transplantation,” “hepatic transplantation,” “liver transplant,” and “hepatic transplant.” We further analyzed these results by the “analyze” function of the software in terms of number of papers for each country, type of documentation, number of publications per year, journal, institute, and author. The number of citations to published works was calculated by using the citation function of the same software. We also used the same function of the software to analyze publications from Turkey in the last three decades between 1980 and 1989, 1990 and 1999, and 2000 and 2009 for statistical evaluation. Collected data from the comparison periods were statistically analyzed using the chi-square test. Results: In all, 48,418 publications related to liver transplantation were included in SCI-E in English between 1980 and August 2011. Overall, 675 of those publications were from Turkey (2.05%). There was no publication from Turkey between 1980 and 1989; 37 between 1990 and 1999; and 511 between 2000 and 2009. The rank of Turkey among other countries according to the number of publications was 25th between 1990 and 1999 and improved to 14th between 2000 and 2009. The number of scientific publications in the field of liver transplantation from Turkey among other countries increased during the last three decades. Conclusions: Turkey showed a significant positive trend in publications in the scientific field of liver transplantation in the last 30 years, and the rank of Turkey among other countries improved in recent decades. Currently, Turkey is one of the top 17 countries in terms of number of scientific publications listed in SCI-E. This can be considered as another indicator for Turkey's progress in the field of liver transplantation.

Long-Term Outcomes of Calcineurin Inhibitor Withdrawal for Post–Liver Transplant Renal Dysfunction

A.J. Mackay, P.W. Angus, P.J. Gow — 2011-12-01

Abstract: Background: It has become common practice to withdraw or reduce calcineurin inhibitors (CNI) in patients with renal dysfunction after liver transplantation; however, little is known about the long-term outcome of this strategy. This study investigates the long-term results of CNI withdrawal for post–liver transplant renal dysfunction and examines for factors that predict a significant improvement in renal function. Methods: A retrospective database review was performed to examine outcomes in patients with CNI withdrawn for chronic renal impairment. Univariate analyses were used to identify predictors of an improvement in creatinine clearance (CrC). Results: Sixty patients (44 males) were included. Of these, 82% of patients were switched to mycophenolate mofetil and 18% azathioprine. Median follow-up after CNI withdrawal was 48 (range 3–72) months. Postwithdrawal, there was an initial improvement in CrCl (mean 5.5 mL), which remained above baseline levels at 6 years. Acute cellular rejection developed in six patients (10%), but there was no rejection-associated graft loss. A shorter time from transplantation to conversion was associated with greatest improvement in CrCI. Conclusions: CNI withdrawal is associated with a significant initial improvement and then arrest in long-term decline of renal function. Rejection in this setting is uncommon. The greatest benefit is seen in patients switched within the early years after transplantation.

Effects of Risk Factors and Ki-67 on Rates of Recurrence on Patients Who Have Undergone Liver Transplant for Hepatocellular Carcinoma

S. Aktas, H. Karakayali, G. Moray, H. Ozdemir, M. Haberal — 2011-12-01

Abstract: Purpose: We investigated the prognostic factors affecting recurrence including Ki-67 among patients who underwent liver transplantation for hepatocellular carcinoma. Materials and Methods: The 50 patients with a diagnosis of hepatocellular carcinoma and cirrhosis included those with expanded criteria for hepatocellular carcinoma excluding subjects with major vascular invasion and metastases but not taking into account tumor size and number of tumor nodules. Results: Twenty-eight patients had hepatocellular carcinoma characteristics outside the Milan criteria. Nineteen patients had unifocal; 31, multifocal hepatocellular carcinomas. Mean tumor size was 3.2 cm; mean tumor number was 5.06 lesions. Over a mean follow-up of 45.3 ± 22.6 months, we diagnosed, respectively 2 recurrences. Overall 1-, 3-, and 5-year patient survival rates were 95.6%, 88.4%, and 84.8% and disease-free survival rates, 92%, 78.4%, and 71%, respectively. The independent prognostic factors by multivariate analyses were the number of tumors and Ki-67 with a cutoff value of 10%. Conclusion: Ki-67 staining percentage represent a marker to select recipients and to follow posttransplant recurrence.

Rate of Tumor Growth Predicts Recurrence of Hepatocellular Carcinoma After Liver Transplantation in Patients Beyond Milan or UCSF Criteria

I.A. Hanouneh, C. Macaron, R. Lopez, F. Aucejo, N.N. Zein — 2011-12-01

Abstract: Background: It is likely that some patients whose tumor burdens exceed the current transplant criteria have favorable tumor biology, and that these patients would have low risk of tumor recurrence after liver transplantation (LT). To assess the rate of tumor growth as selection criteria for LT in patients with hepatocellular carcinoma (HCC). Methods: We identified all patients who underwent LT for HCC in our institution from 2002 to 2008. Total tumor volume (TTV) was calculated as the sum of the volumes of all tumors on pretransplantation imaging [(4/3)πr3, where r is the maximum radius of each HCC]. The rate of tumor growth was calculated as per-month change in TTV on sequential pretransplantation imaging before any locoregional therapy. A Kaplan-Meier plot was constructed and Cox regression analysis performed. Results: Ninety-two patients were included in the study. The median follow-up was 19.5 (range 10.7–30.7) months during which 12 patients (13%) experienced recurrence of HCC. Twenty-four patients (26%) had HCC beyond the Milan criteria, and the overall survival rate of the entire group was 72%. Higher pre-LT alpha-fetoprotein (hazard ratio [HR] 1.01; P = .001), poorly differentiated tumors (HR 13; P = .039), the presence of microvascular invasion (HR 7.9; P = .001), higher TTV (HR 1.03; P < .001), and faster tumor growth (HR 1.09; P < .001) were significantly associated with the risk of recurrence. A cutoff value of tumor growth of 1.61 cm3/mo was chosen on the basis of the risk of recurrence with the use of a receiver operating characteristic curve. Patients beyond the Milan criteria with tumor growth <1.61 cm3/mo experienced less recurrence (11% vs 58%; P = .023) than those beyond the Milan criteria with tumor growth >1.61 cm3/mo. Similarly, rate of tumor growth predicted HCC recurrence in those beyond the University of California of San Francisco (UCSF) criteria. Conclusions: Patients with slowly growing tumor who would be currently excluded from LT because tumor burden exceeds traditional Milan and UCSF criteria may have a favorable posttransplantation outcome.

Liver Graft Failure and Hyperbilirubinemia in Liver Transplantation Recipients After Clostridium difficile Infection

C. Rochon, A. Kardashian, B. Mahadevappa, G. Gunasekaran, J. Sharma, P. Sheiner — 2011-12-01

Abstract: Introduction: Liver transplant recipients are at high risk for Clostridium difficile infection. We have recently encountered multiple cases of CDI in our liver transplant recipients and for some of them it led to severe hyperbilirubinemia, liver failure, and even death. Our goals are to report our experience and analyze the factors that contributed to unfavorable outcomes. Material and Methods: All liver transplant recipients diagnosed with CDI between December 1, 2007, and January 30, 2009, were included and retrospectively reviewed. Results: Twenty-four patients were identified, 14 men and 10 women. Fourteen patients experienced hyperbilirubinemia after the infection and 7 progressed to liver failure. Pre-CDI biopsy-proven liver abnormality, use of extended-criteria donors (ECDs) and a donor risk index (DRI) greater than 1.9 were associated with a higher risk of graft failure (P < .05). Hepatitis C, inpatient versus outpatient diagnosis, and a donor age greater than 50 years were not associated with a higher risk of graft failure. Use of ECDs and timing of the infection at more than 1 month but less than 1.5 years posttransplant were also associated with higher chances of sustained hyperbilirubinemia (P < .05). Conclusion: CDI in liver transplant patients can be very serious and may lead to sustained hyperbilirubinemia or graft failure. Marginal grafts are more susceptible to decompensate after such an infection than standard criteria grafts; moreover, already abnormal grafts do not tolerate this infection well and decompensate to complete failure in 85% of the cases.

The Effect and Safety of the Treatment of Recurrent Hepatitis C Infection After Orthotopic Liver Transplantation With Pegylated Interferon α2b and Ribavirin

2011-12-01

Abstract: Introduction: Recurrent hepatitis C infection in the posttransplant setting is a serious problem. The aim of this study was to evaluate the efficacy, safety, indications, optimal time of administration and adequate duration of antiviral therapy with pegylated interferon alpha 2 b (PEG-IFN) and ribavirin (RIB). Patients and methods: Between 2003 and 2009, 16 patients received antiviral therapy (PEG-IFN: 0.8–1.6 μg/kg/wk, RIB 800–1200 mg/d) for at least 6 months. Patients with a biochemical without a virologicalresponse after 12 months of therapy received antiviral treatment for a further 6 months. Hepatitis C virus load was determined at 1, 3, 6, and 12 months after start of therapy. Liver biopsy was performed in all patients before the beginning and after the end of treatment. Results: The mean period of antiviral therapy was 14 months. The four patients who received the full-length treatment (12 months, 33%) showed sustained virological responses (SVR) and 8 showed virological and biochemical responses (VR, BR). Patients with SVR showed significant improvement in the grading and staging of HAI (histological activity index; P = .03). Nine patients had several side effects under antiviral treatment. Acute rejection episodes were not observed. Conclusion: The antiviral treatment combination using PEG-IFN and RIB for recurrent hepatitis C is effective procedure. The SVR of 33% after 12 months of treatment with significant improvement in HAI grading and staging and stable HAI in all treated patients favor early initiation and 12-month administration of antiviral treatment. Furthermore, all patients with BR without VR, who underwent antiviral treatment for a further 6 months, achieved a VR. However, the optimal duration of treatment needs to be investigated in large prospective studies.

Portal Vein Stenosis: A Rare Yet Clinically Important Cause of Delayed-onset Ascites after Adult Deceased Donor Liver Transplantation: Two Case Reports

N. Schneider, A. Scanga, L. Stokes, R. Perri — 2011-12-01

Abstract: Vascular complications following liver transplantation are well documented. While complications involving the portal vein are less common than the hepatic artery, portal vein complications can lead to potentially life-threatening sequelae including graft loss. Portal vein stenosis is an infrequent complication following liver transplant. The majority of these complications are seen in living donor liver transplants and pediatric liver transplants. We present 2 cases of delayed onset portal vein stenosis in adult deceased donor liver transplantation (ADDLT). The first patient presented with refractory ascites twelve months after ADDLT. He was diagnosed and successfully treated with percutaneous transhepatic portovenography and venoplasty. The second patient had a history of irradiation to his portal bed in the setting of cholangiocarcinoma. He developed refractory ascites and esophageal variceal bleeding >2 years after ADDLT. He underwent percutaneous transhepatic portovenoplasty, but eventually required placement of a portal stent due to continued problems with recurrent ascites. These 2 cases highlight the importance of considering portal vein stenosis in the differential diagnosis of late-onset ascites following liver transplantation, especially if there have been any predisposing risk factors such as portal bed irradiation or prior splenectomy.

Factors Influencing Posttransplantation Employment: Does Depression Have an Impact?

2011-12-01

Abstract: Background: Depressive disorders are the leading cause of disability in the United States. Liver transplant recipients often have significant psychiatric morbidity, including depression. One of the potential consequences of depression is the inability to work. Objective: The objective of this study was to determine if there is any relationship between depression and posttransplantation employment status in liver transplant recipients. Methods: Patients, 18 years of age or older, who had received liver transplants from January 2007 to July 2009 were identified for the retrospective analysis. Individual posttransplantation patient charts were reviewed for patient demographics, transplantation indication, employment history, depression diagnosis, and medications. The pretransplantation charts were used to obtain family psychiatric history, patient psychiatric history, past drug, alcohol, and tobacco use, and pretransplantation employment status. Results: A total of 91 patients were evaluated, of which 59.3% were males and 40.7% were females, with a mean age of 56 years. In our sample, 23% and 29% of patients were depressed pretransplantation and posttransplantation, respectively. The number of unemployed patients also increased from 10.9%–23.1%. A logistic regression was performed to identify the factors influencing employment posttransplantation, which indicated pretransplantation employment, gender (males more likely to return to work), and depression post transplantation as significant factors with odds rations of 128, 4.1, and 11.5 and corresponding P values of <.0001, .04 and .008, respectively. Conclusion: Posttransplantation depression is significantly associated with post–liver transplantation unemployment. Improved management of depression may facilitate a patient's return to work after transplantation.

Effect of Pretransplant Human Leukocyte Antigen Antibodies Detected by Solid-Phase Assay on Heart Transplant Outcomes

2011-12-01

Abstract: Introduction: The significance of pretransplant human leukocyte antigen antibodies (HLA-Abs), especially donor-specific HLA-Abs (DSA), as detected by single antigen bead assay (SAB), is not well characterized in cardiac transplantation (CTX). We analyzed the significance of DSA detected by SAB in predicting crossmatch (XM) results and post-transplant rejection. Materials and methods: We performed a retrospective study of 85 CTX with negative cytotoxicity XM. We tested pretransplant sera collected within 24 hours of transplantation by flow cytometric XM (FXM) and SAB. DSA identified by SAB were utilized to perform a virtual crossmatch (VXM). Positive VXM was defined as the presence of DSA at mean fluorescence intensity (DMFI) > 1500. Additionally, to analyze the significance of low-level DSA weakly positive VXM was DMFI 300 to 1500. We defined a negative VXM as MFI < 300. VXM results were correlated with FXM results and with posttransplant rejection. Results: Patients in the weakly positive and negative VXM had similar posttransplant rejections. DMFI > 1500 correlates well with FXM results (accuracy = 90%). Patients with DMFI > 1500 had a higher incidence of antibody-medicated rejection (AMR; P = .0052), AMR grade I (P < .0001), cell-mediated rejection (CMR) grade > 1R/1A (P = .018), and CMR grade > 2R/3A (P = .057). Similarly patients with positive FXM had a higher incidence of AMR (P = .091), AMR grade 1 (P < .0001), CMR grade > 1R/1A (P = .05), and CMR grade > 2R/3A (P = .56). Conclusions: In conclusion, SAB defined DMFI > 1500 can be used as a surrogate for FXM. Recipients with DMFI > 1500 pretransplant and positive FXM have significantly higher rates of AMR and CMR compared to recipients with DMFI < 1500 or negative FXM.

Comparison of Heart Transplantation Patients with Ischemic and Idiopathic Dilated Cardiomyopathy

2011-12-01

Abstract: Objective: We retrospectively analyzed our data to compare preoperative demographic, laboratory, echocardiographic, hemodynamic findings mortality and survival rates of heart transplantation patients with ischemic (ICM) and idiopathic dilated (IDCM) cardiomyopathy. Methods: The data of 144 patients transplanted from February 1998 to January 2011 were analyzed. 38 patients with ischemic ICM and 86 patients with IDCM were compared. Results: Recipient age, preoperative creatinine, recipient body mass index, intraoperative cross-clamp time, donor male sex ratio, recipient male sex ratio, hyperlipidemia ratio, and previous nitrate use were significantly higher and left ventricular end systolic diameter significantly lower in patients with ICM. Major causes of death after heart transplantation were infections (31.9%), right ventricle failure (14.8%), and sudden cardiac death (14.8%). Causes of death were not different between the groups. Overall mortality in the entire population was 37.9% (47/124), and it was not different between the groups (39.5% vs 37.2%; P = .48). Early mortality (<30 days) rate was 11.2% (14/124), late mortality rate was 26.6% (33/124), and no statistically significant difference was observed between the groups. Survival analysis showed that ICM patients were not associated with worse survival compared with IDCM (71.1% vs 81.1% after 1 year, 68.1% vs 73.0% at 2 years, and 54.2% vs 62.3% at 5 years; log rank = 0.57). Multivariate analysis showed that the only predictor of mortality was preoperative urea level and that heart failure etiology was not a predictor of this end point. Conclusions: Patients with ICM had similar survival and mortality rate compared with IDCM.

Heart Transplantation in Patients Aged 70 Years and Older: A Two-Decade Experience

2011-12-01

Abstract: Objective: Advanced age has been viewed as a contraindication to orthotopic heart transplantation (OHT). We analyzed the outcome of OHT in patients who were aged 70 years or older and compared the results with those in younger patients during a two-decade period. Methods: A total of 519 patients underwent first-time single-organ OHT at our institution from 1988 to 2009. Patients were divided into three groups by age: ≥ 70-years old (group 1, n = 37), 60 to 69-years old (group 2, n = 206), and ≤60-years old (group 3, n = 276). Primary endpoints were 30-days, and 1-, 5-, and 10-years survival. Secondary outcomes included re-operation for bleeding, postoperative need for dialysis, and length of postoperative intubation. Results: There was no significant difference in survival between the greater than or equal to 70-year-old group and the two younger age groups for the first 10 years after OHT. Survival rates at 30 days, and 1-, 5-, and 10-years, and median survival in group 1 recipients were 100%, 94.6%, 83.2%, 51.7%, and 10.9 years (CI 7.1–11.0), respectively; in group 2 those numbers were 97.6%, 92.7%, 73.8%, 47.7%, and 9.1 years (CI 6.7–10.9), respectively; and in group 3 those numbers were 96.4%, 92.0%, 74.7%, 57.1%, and 12.2 years (CI 10.7–15.4; P = NS), respectively. There was no significant difference in secondary outcomes of re-operation for bleeding, postoperative need for dialysis, and prolonged intubation among the three age groups. Conclusions: Patients who are aged 70 years and older can undergo heart transplantation with similar morbidity and mortality when compared with younger recipients. Advanced heart failure patients who are aged 70 years and older should not be excluded from transplant consideration based solely on an age criterion. Stringent patient selection, however, is necessary.

Exercise Performance Comparison of Bicaval and Biatrial Orthotopic Heart Transplant Recipients

2011-12-01

Abstract: Background: The standard biatrial technique for orthotopic heart transplantation uses a large atrial anastomosis to connect the donor and recipient atria. A modified technique involves bicaval and pulmonary venous anastomoses and is believed to preserve the anatomic configuration and physiological function of the atria. Bicaval heart transplantation reduces postoperative valvular regurgitation and is associated with a lower incidence of pacemaker insertion. Objective: The aim of this study was to compare postoperative functional capacity and exercise performance in patients with bicaval and biatrial orthotopic heart transplantation. Methods: Patients were selected for the study if they did not have any of the following: obstructive coronary artery disease (>50% stenosis), severe mitral or tricuspid regurgitation, signs of rejection (grade ≥1B-1R) on endomyocardial biopsy during the prior year, respiratory impairment, a permanent pacemaker, orthopedic or muscular impediments, or lived more than 150 miles from the medical center. A total of 27 patients qualified. In 15 patients who received a biatrial heart transplant and 12 patients with a bicaval heart transplant, a stationary bicycle exercise test was performed. Ventilatory gas exchange and maximum oxygen consumption measurements were measured. Results: Recipient and donor characteristics, including body surface area, donor/recipient weight mismatch, immunosuppressive regimen, and self-reported weekly exercise activity, did not differ between the biatrial and bicaval groups (P = not significant [NS]). At peak exercise, similar heart rate, workload, oxygen consumption, carbon dioxide production, ventilation, functional capacity, and exercise duration were found between the 2 groups (P = NS). Patients in the biatrial group were studied later than patients in the bicaval group (6.54 ± 0.71 vs 4.68 ± 0.28 years; P < .001). Conclusion: There were no significant differences in the exercise capacity between patients with biatrial versus bicaval techniques for orthotopic heart transplantation. Factors other than the atrial connection (such as cardiac denervation, immunosuppressive drug effect, or physical deconditioning) may be more important determinants of subnormal exercise capacity after heart transplantation. Nevertheless, the reduction in morbidity and postoperative complications and the simplicity in the bicaval technique suggest that bicaval heart transplantation offers advantages when compared with the standard biatrial technique.

Prolonged Cold Ischemic Times and Less Donor-Recipient Histocompatibility Accelerate Graft Vascular Disease

L.S.C. Czer, A.V. Wong, H. Soukiasian, S. Gallagher, M. De Robertis, A. Trento — 2011-12-01

Abstract: Introduction: The long-term success of cardiac transplantation is limited by graft atherosclerosis, also known as graft vascular disease (GVD). GVD is currently the leading cause of late allograft failure in cardiac transplant recipients. The aim of this study was to assess the effects of cold ischemic preservation time (CIPT) and degree of donor-recipient histocompatibility on GVD using a rat heterotopic cardiac transplantation model. Methods: ACI-Lewis (n = 9), Lewis-F344 (n = 9), and Lewis-Lewis (n = 9) donor-recipient rat strain combinations were subjected to variable durations of CIPT (0, 4, and 24 hours in University of Wisconsin solution at 4°C) prior to transplantation (n = 81 total). The ACI-Lewis allografts differed in both major histocompatibility complex (MHC) class I and II antigens, the Lewis-F344 allograft combination differed in multiple non-MHC antigens, and the Lewis-Lewis isograft combination was syngeneic. Grafts were harvested at 90 days. Intimal area ratio (IAR), intimal thickness score (ITS), and rejection score (RS) were determined for each specimen. Results: The Lewis-Lewis transplant group had a significantly higher mean RS (P = .036) with 24 hours than with 0 hours of CIPT in this rat heterotopic transplantation model at 90 days. The Lewis-F344 group had a significantly higher IAR (P = .035), ITS (P = .030), and RS (P = .017) with 24 hours than with 0 hours of CIPT. The ACI-Lewis group had high levels of GVD with all durations of CIPT (0, 4, and 24 hours); as a consequence, there were no significant differences in the ITS, IAR, or RS. With 0 hours of CIPT, the ACI-Lewis transplantation group yielded a significantly higher mean IAR (P = .029), ITS (P = .003), and RS (P = 5.02 × 10−5) than the Lewis-Lewis group. The Lewis-F344 group had a significantly higher mean RS (P = .003) than the Lewis-Lewis (syngeneic) group. The ACI-Lewis transplantation group had a significantly higher mean IAR (P = .035), and trended toward a higher ITS (P = .058) than the Lewis-F344 group. Conclusion: Longer cold ischemic preservation time and less donor-recipient histocompatibility were associated with more advanced GVD in a rat heterotopic transplantation model, especially when there were multiple MHC mismatches as in ACI-Lewis allografts, but also occurred when there were differences in multiple non-MHC antigens as in the Lewis-F344 allografts. There was a lesser effect of longer cold ischemic time on GVD in the Lewis-Lewis syngeneic (isograft) group, suggesting that greater histocompatibility can mitigate the adverse effects of longer ischemic times.

Survival and Allograft Rejection Rates after Combined Heart and Kidney Transplantation in Comparison with Heart Transplantation Alone

2011-12-01

Abstract: Background: The role of solid multiorgan transplantation remains to be determined. We compared our experience with combined heart-kidney transplantation (HKT) and heart transplant alone (HT), and assessed patient survival rates and freedom from allograft rejection in these two patient groups. Methods: We reviewed the clinical outcomes of patients undergoing HKT (n = 30) or HT (n = 440) between June 1992 and March 2009. Baseline patient characteristics, perioperative factors, incidence of rejection, and survival were examined. Results: There were no significant differences between the two groups for age, gender, etiology of heart disease, functional class, preoperative left ventricular ejection fraction, end-diastolic diameter, cardiac output, or transplant waitlist status. Patients with HKT had a higher serum creatinine level (P < .001) and a greater incidence of hypertension (P = .04). No differences were found in cardiac allograft ischemic times, including cardiopulmonary bypass or cross-clamp times. Kidney allograft ischemic time was 14.6 ± 9 hours (mean ± SD; range, 4 hours to 49 hours). Kaplan-Meier survival estimates were similar for the HKT and HT groups at 30 days (93% ± 4.6% versus 98% ± 0.7%), 1 year (87% ± 6.2% versus 93% ± 1.2%), 5 years (68% ± 9.0% versus 76% ± 2.1%), and 10 years (51% ± 11% versus 53% ± 3.0%; P = .54 for all comparisons). Follow-up serum creatinine levels were similar after HKT and HT at 30 days (1.6 ± 1.8 mg/dL versus 1.1 ± 0.4 mg/dL), 1 year (1.4 ± 0.6 mg/dL versus 1.5 ± 0.6 mg/dL), and 5 years (1.8 ± 1.8 mg/dL versus 1.8 ± 1.2 mg/dL; P > .05 for all comparisons). Conclusions: HKT offers excellent survival and similar renal function when compared with HT alone. Patients with end-stage cardiac and renal failure can be considered for HKT.

Noninvasive Diagnosis of Cardiac Allograft Rejection Using Echocardiography Indices of Systolic and Diastolic Function

2011-12-01

Abstract: Background: Limited and conflicting data exist on the diagnosis of cardiac allograft rejection with the use of echocardiography. The purpose of our study was to evaluate various systolic and diastolic indices, including newer tissue Doppler imaging techniques, in diagnosing cardiac allograft rejection. Methods: We prospectively performed 426 echocardiography studies at the time of endomyocardial biopsy in 54 cardiac transplant patients. We measured left ventricular (LV) systolic and diastolic dimensions, mitral inflow pattern and annular velocities, and the myocardial performance index. Biopsies were assessed for cellular rejection and antibody-mediated rejection (AMR). Results: Mild cellular rejection was diagnosed in 74 biopsy specimens and significant cellular rejection in 10 biopsy specimens. AMR was diagnosed in 30 biopsy specimens. In patients with mild or significant cellular rejection, no significant differences in echocardiographic parameters were observed. In patients with AMR, LV fractional shortening was significantly reduced compared with those with no AMR (mean ± SD 31.8 ± 8.9% vs 36.0 ± 7.1%; P = .02). Conclusions: Although 1 echocardiographic parameter was statistically different in the setting of rejection, lack of consistency and overlap between nonrejection and rejection groups does not permit definitive noninvasive diagnosis of cardiac allograft rejection using this imaging modality.

Successful Use of the TandemHeart Percutaneous Ventricular Assist Device as a Bridge to Recovery for Acute Cellular Rejection in a Cardiac Transplant Patient

2011-12-01

Abstract: In this report, we presented a patient who benefited from hemodynamic support with the TandemHeart Percutaneous Ventricular Assist Device (pVAD; Cardiac Assist, Inc) implantation in the setting of early acute graft rejection 2 months after orthotopic heart transplant. The TandemHeart initially had been used for temporary hemodynamic assistance during postcardiotomy heart failure and high-risk coronary interventions. More recently, its use in patients with cardiogenic shock from acute myocardial infarction, fulminant myocarditis, and critical aortic stenosis has been reported. To our knowledge, this is one of the first reported cases in which the TandemHeart pVAD served as a successful device for support during acute cardiac transplant rejection.

Prevalence of Iron Deficiency in Heart and Kidney Allograft Recipients

2011-12-01

Abstract: Background: Functional iron deficiency is characterized by the presence of adequate iron stores as defined by conventional criteria, but insufficient iron mobilization to adequately support erythropoiesis. The aim of this study was to assess the prevalence of functional iron deficiency in heart and kidney transplant recipients based on data from recent medical records. Methods: Using standard laboratory methods obtained during routine checkups, we assessed iron status by determinations of serum iron, total iron-binding capacity, ferritin and total saturation of transferrin (TSAT), as well as complete blood count and creatinine. Results: Iron parameters were available for 62% of heart transplant recipients, but only for 26% of kidney transplant recipients. Absolute iron deficiency was observed in 35% of the heart and 8% of the kidney transplant recipients (P < .001). Functional iron deficiency was present in 4% of the heart and 6% of the kidney transplant recipients. Functional iron deficiency was associated with significantly higher serum ferritin and lower TSAT. In addition, although their hemoglobin values did not differ significantly, heart transplant recipients with absolute iron deficiency showed lower erythrocyte blood counts, were younger, and had a shorter time after transplantation. Conclusions: Iron parameters are assessed infrequently, particularly among kidney transplant recipients. Iron deficiency was present in a considerable group of heart transplant recipients. This population should be carefully screened for possible reversible causes of iron deficiency to slow or to minimize anemia development.

Serum Renalase Depends on Kidney Function But Not on Blood Pressure in Heart Transplant Recipients

2011-12-01

Abstract: Introduction: Renalase, an enzyme that breaks down catecholamines like adrenaline and noradrenaline in the blood circulation, was discovered in 2005. The human kidney releases this protein into the bloodstream to regulate blood pressure. Heart transplant recipient show a high prevalence of hypertension. The aim of this study was to assess possible correlations between renalase, blood pressure, and kidney function among 130 prevalent heart transplant recipients. To obtain normal ranges we also studied renalase levels in 27 healthy volunteers. Methods: Complete blood counts, urea, serum lipids, fasting glucose, and creatinine were measured using standard laboratory methods in the hospital central laboratory. Renalase was assessed using commercially available kits. Results: In heart transplant recipients renalase levels correlated with age (r = 0.25; P < .05); time after transplantation (r = 0.22; P < .05); serum creatinine (r = 0.85; P < .001); estimated glomerular filtration rate (chronic kidney disease-epidemiological study formula; r = 0.59; P < .0001; Modification of Diet of Kidney Disease (r = −0.58; P < .001); Cockcroft-Gault (r = −0.59; P < .001); 24-hour creatinine clearance (r = −0.52; P < .001); NT-proBNP (r = 0.41; P < .001); erythrocyte count (r = −0.42; P < .001); hemoglobin (r = 0.44; P < .001); cystatin C (r = 0.82; P < .001); ejection fraction (r = −0.26; P < .01; and New York Heart Association class (r = 0.31; P < .001). Multiple regression analysis showed renalase concentration to be predicted in 75% by serum creatinine (beta value, 0.79; P = .0000000; SE 3.00; F statistics 15.96; P < .0000001). Serum renalase was higher among heart transplant recipients than healthy volunteers. Conclusion: Renalase, highly elevated in heart transplant recipients, is predominantly dependent on kidney function, which deteriorates with time after heart transplantation and age. Further studies are needed to establish its putative role in the pathogenesis of hypertension after transplantation and possible novel targeted therapies. However, is seems that among heart transplant recipients renalase was not related to blood pressure.

Cumulative Exposure to CD8+ Granzyme Bhi T Cells Is Associated with Reduced Lung Function Early after Lung Transplantation

2011-12-01

Abstract: Outcomes following lung transplant remain suboptimal. This is attributable to variable posttransplant recovery of lung function, and inconsistent degrees of lung function loss after peak function is reached. Granzyme B is elevated in the blood and bronchoalveolar lavage (BAL) in acute rejection. We hypothesized that persistent exposure to T cells high in granzyme B would negatively correlate with lung function. We investigated cumulative exposure measured as the area-under-the-curve (AUC) of CD8+ T cell granzyme Bhi cells in the first year posttransplant in both BAL and blood in 24 transplant recipients. We assessed the correlation between cumulative 1-year exposure and FEV1 slope. There was a negative correlation between 1-year exposure and FEV1 slope within the first year (r = −0.63; P = .001). This relationship persisted even when adjusted for transplant type, gender, age, rejection, and indication for transplantation. In contrast, no relationship was seen with the 1-year AUC and lung function after 1 year posttransplant. In contrast to the BAL granzyme Bhi levels, granzyme Bhi levels from the blood showed no relationship with lung function. These findings suggest that CD8+ T-cell–driven factors are responsible for early improvements in lung function after transplantation.

Influence of Gender Donor-Recipient Combinations on Survival After Human Lung Transplantation

D. Fessart, C. Dromer, M. Thumerel, J. Jougon, F. Delom — 2011-12-01

Abstract: Background: In the current practice of lung transplantation, donor and recipient genders are neither directly considered nor matched. However, some data have suggested a possible effect of gender combinations on survival following lung transplantation. Methods: A total of 249 adult lung transplant recipients at a single center between February 1988 and December 2008, were analyzed retrospectively for donor-recipient gender matching. We compared the mortality by calculating one-term survival rates after transplantation using the Kaplan-Meier method with comparisons using the log-rank (Mantel-Cox) test. Statistical significance of the mean effects of size matching was assessed by paired Student t tests and Wilcoxon signed rank tests. Results: Kaplan-Meier survival analysis shown that male compared to female recipients did not have an effect on outcomes after lung transplantation at 5 years (P = .5379), 10 years (P = .107), 15 years (P = .0841), 20 years (P = .0711). No effect of gender on lung transplantation outcomes was observed with donor-recipient gender mismatches at 5 years (P = .1804), 10 years (P = .1457), 15 years (P = .0731), or 20 years (P = .0629). Similarly, no differences were observed for each gender combination. The degree of size matching was defined as the ratio of donor-to-recipient predicted total lung capacity. The ratios were similar for the donor-recipient gender match and significantly different for the donor-recipient gender mismatch. Conclusions: These analyses suggested that gender was not a significant independent risk factor affecting survival after lung transplantation. Size mismatch caused by gender mismatch did not increase mortality.

Simultaneous Pancreas Kidney Transplantation in the HIV-Positive Patient

M.Z. Akhtar, N. Patel, A. Devaney, S. Sinha, S. Shankar, A. Vaidya, P.J. Friend — 2011-12-01

Abstract: HIV is no longer an absolute contraindication to solid organ transplantation. However, few reports have been published with regards to pancreas or simultaneous pancreas kidney transplantation in the HIV-positive recipient. We report, to our knowledge, the first simultaneous pancreas kidney transplantation (SPK) performed in an HIV-positive patient in the United Kingdom. We reflect on the article recently published by Miro et al in Transplantation Proceedings and highlight strategies used by our department to prevent drug interactions in these complex patients.

Gastroduodenal Arterial Reconstruction of the Pancreaticoduodenal Allograft

J.Q. Li, Z.J. He, Z.Z. Si, W. Hu, Y.N. Li, H.Z. Qi — 2011-12-01

Abstract: Simultaneous procurement of the pancreas and liver necessitates division of vessels supplying both organs. The integrity of the pancreatic arterial supply appears to be related to surgical complications after pancreas transplantation. We have described herein three cases of gastroduodenal artery (GDA) reconstruction during pancreas transplantation, and reviewed other options for GDA reconstruction. These techniques performed safely during bench reconstruction can be applied to various clinical situations.

Effects of Astragalosides on Cultured Islets After Cryopreservation in Rats

2011-12-01

Abstract: Objective: To explore the effects of AST (astragalosides) on cultured rat islet yield, purity, and function after cryopreservation in rats. Methods: Pancreatic islets were isolated from 30 Sprague-Dawley rats using the standard technique of collagenase P digestion and discontinuous Ficoll gradient purification. After thaw, the islets were randomly divided into AST group and control group (n = 15). Next, the islet cells were cultured in AST-containing medium or standard medium for 7, 14, and 21 days after cryopreservation and thaw. The quantity, purity, and survival rate were calculated in the two groups before and after culture. Then the in vitro and in vivo function was observed in diabetic rats after islet transplantation. Results: The quantity and purity of islets had no difference between the two groups before culture (P > .05) while the difference after culture was significantly (P < .05). The survival rate of islets was 48% in AST group and 32% in the control group 21 days after thaw (P < .05). After 3 days, there was significantly a higher simulation index in the AST group than in the control group (P < .05). There was a significant difference in blood glucose and insulin concentrations between the groups after 3 days (P < .05). Conclusion: AST can be added to the culture medium to reduce the loss of islet cryopreservation and be intravenously injected to improve culture islet function in vitro and prolong islet graft survival in diabetic rats.

High Expression of Fas Ligand on Cord Blood Dendritic Cells: A Possible Immunoregulatory Mechanism After Cord Blood Transplantation

N. Naderi, S.M. Moazzeni, A.A. Pourfathollah, K. Alimoghaddam — 2011-12-01

Abstract: Background: Allogeneic cord blood transplantation is associated with less severe graft-versus-host disease (GVHD). Dendritic cells (DCs), as the most potent antigen-presenting cells of the immune system, play a central role in the development of GVHD. Because apoptosis induction is one of the known mechanisms that DCs use to regulate T-cell responses, we studied the immunostimulatory and apoptosis induction capacities of cord blood dendritic cells (CBDCs) and peripheral blood dendritic cells (PBDCs) to evaluate the mechanisms underlying the lower incidence of GVHD after cord blood transplantation. Presence of apoptosis-related markers Fas, Fas ligand (FasL), and CD40 and costimulatory molecules, along with the proportion of myeloid and lymphoid DCs subsets, were also measured on CBDCs and PBDCs. Methods: Fresh CBDCs and PBDCs were isolated from cord and peripheral mononuclear cells as lineage-negative cells by using monoclonal antibodies against CD3, CD11b, CD14, CD16, CD19, CD56, CD34, and CD66b. DCs were cocultured with allogeneic T cells, and the effect of CBDCs and PBDCs on T-cell apoptosis and proliferation were determined through flow cytometric analysis and 3H-thymidine incorporation. Results: Our findings showed that CBDCs markedly augment apoptosis of CD3+ T-cells. FasL expression on CBDCs was significantly higher than on PBDCs. However, there was no difference between Fas expression on CBDCs and PBDCs. Moreover, CBDCs were poor stimulators of allogenic T cells in mixed leukocyte reaction compared with adult peripheral blood DCs. They also displayed decreased expression of HLA-DR and CD86 molecules. The ratio of lymphoid DCs (CD11c−, CD123+) to myeloid DCs (CD11c+, CD123−) was also significantly higher in CBDCs compared with PBDCs. Conclusions: It seems that less severe GVHD after cord blood transplantation is due not only to a higher degree of immaturity of CBDCs, but also to delivery of apoptotic signals to the host T cells that recognize allo-MHC molecules on CBDCs in the early phase of immune response.

Imbalance Between Bone Formation and Resorption in Hematopoietic Stem/Progenitor Cells Mobilization

S.-D. Li, Q.-L. Zhai, L.-G. Qiu — 2011-12-01

Abstract: Mobilization is now used worldwide to collect large numbers of hematopoietic stem and progenitor cells (HSPCs) for transplantation. It is the result of a process impelling stem cell detachment from their niche, meanwhile gaining cellular features required for proliferation and migration. Mobilization remarkably affects the endosteal stem cell niche, which must be adjusted to support retention and quiescence versus mobilization and proliferation. The endosteal bone-lining cells, osteoblasts and osteoclasts, not only maintain bone balance but also participate in HSPC mobilization. The aim of this paper was to review recent advances in our understanding of HSPC mobilization and how these advances are being translated into the clinic for more efficacious mobilizing agents.

Immunoglobulin Prophylaxis Against Cytomegalovirus Infection in Patients at High Risk of Infection Following Allogeneic Hematopoietic Cell Transplantation

2011-12-01

Abstract: Reports on the efficacy of intravenous immunoglobulin (IVIG) prophylaxis against cytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplantation (HCT) have often sparked controversy. In addition, we are not aware of any study that has examined whether prophylaxis with IVIG affects the incidence of CMV infection in high-risk patients—those who are elderly or have received human leukocyte antigen (HLA) mismatched HCT. In the present open-label, phase II study, we addressed this question. We enrolled 106 patients in the study. The cumulative incidences of CMV infection at 100 days after HCT were similar in the intervention and the control groups (68% and 64%, P = .89; 89% and 87%, P = .79, respectively, for patients 55 years or older and those who received HLA-mismatched HCT). In those who received HLA-mismatched HCT, 1-year overall survival after HCT was 46% in the intervention group and 40% in the control group (P = .31); for age ≥ 55 years, the corresponding values were 46% and 40% (P = .27). Our data showed that prophylaxis with regular polyvalent IVIG did not affect the incidence of CMV infections or survival among older patients or those who receive HLA-mismatched HCT.

Galectin-3 Enhances Proliferation and Angiogenesis of Endothelial Cells Differentiated from Bone Marrow Mesenchymal Stem Cells

S.Y. Wan, T.F. Zhang, Y. Ding — 2011-12-01

Abstract: Purpose: To observe the effects of galectin-3 on proliferation and angiogenesis of endothelial cells differentiated from bone marrow mesenchymal stem (MSCs). Methods: Cultured MSCs were isolated from bone marrow of Sprague–Dawley rats and purified by gradient centrifugation with lymphocytes separation medium. Cells of passage 3 were differentiated into endothelial cels by vascular endothelial growth factor and basic fibroblast growth factor. These cells were identified as endothelial cells by immunohistochemistry staining and electronic microscopy after 14 days. The cells were cultivated with the galectin-3 at the concentrations of 0.1, 1, and 5 μg/mL for 24 hours. The proliferation of endothelial cells were measured by 3-(4,5-methylth-iazol-2-yl)-diphenyltetrazolium bromide (MTT) and the cell cycle was investigated by using flow cytometry. The functionality of angiogensis was observed when the cells appeared tube formation in presence of glacetin-3. Results: The proliferation activity, analyzed by MTT method, in the galectin-3 groups (1 and 5 μg/mL) were 0.3002 ± 0.0159 and 0.3514 ± 0.0133, respectively, which were significantly greater than that in the control group (0.2339 ± 0.0041; P < .05). Flow cytometry detection showed that S phase cells (%) are 29.42 ± 0.45, 34.56 ± 0.82, and 52.58 ± 2.84 in groups of 0.1, 1, and 5 μg/mL, respectively, and G2M phase cells increased from 4.88 ± 1.12 to 5.26 ± 0.45 with the concentrations of 1 and 5 μg/mL, respectively, which demonstrated significant difference compared with the control group (P < .05). The tubular network formation was lengthened significantly compared with the control group (P < .05). Conclusion: Galectin-3 can promote the proliferation and angiogenesis of endothelial cells differentiated from bone marrow mesenchymal stem cells.

Oxidative Stress Indices in Rats Under Immunosuppression

2011-12-01

Abstract: Immunosuppressants lead to generation of reactive oxygen species (ROS). Oxidative stress (OxS) can initiate chronic allograft nephropathy (CAN). The most active antioxidant enzymes, superoxide dysmutase (SOD) and catalase (CAT), are present in erythrocytes. Glutathione peroxidase (GPx) is produced in the proximal tubules of nephrons. Malonyldialdehyde (MDA) concentrations are a marker of OxS intensity in plasma. In vitro and animal model studies have shown increased or decreased OxS during treatment with tacrolimus (Tac) or cyclosporine (CyA). Results obtained in humans after solid organ transplantation have been contradictory, because of confounding factors such as ischemia-reperfusion injury, donor and recipient ages, endothelial injury, and comorbidity. The aim of this study was to assess the intensity of OxS among rats under chronic immunosuppression (IS) without a transplantation. We examined 49 male Wistar rats. IS started at 12 weeks of age was continued for 6 months: group I were controls (n = 7); group II, Tac + sirolimus (Rapamycin [Rapa]) + corticosteroids (CS; n = 6); group III, CyA + Rapa + CS (n = 4 of which 2 died); group IV, Rapa + mycophenolate mofetil (MMF) + CS (n = 6); group V, CyA + MMF + CS (n = 6); group VI, CsA + MMF + CS for 3 months followed by conversion to Rapa (n = 6); group VII, Tac + MMF + CS (n = 6 rats); and group VIII, Tac + MMF + CS for 3 months followed by conversion to Rapa (n = 6). The drug doses were as follows: Tac 4 mg/kg/d; MMF 20 mg/kg/d; CyA 5mg/kg/d; Rapa 0.5mg/kg/d; and CS 4 mg/kg/d. Multiple regression analysis revealed that all IS drugs decreased GPx activity (P < .001) except CS, which increased it (P < .0001). Multiple regression analysis showed that CsA and Tac decreased plasma MDA concentrations (P < .01), whereas CS increased them (P < .05). In conclusion, all IS drugs except CS damage proximal tubules of nephrons.

Donor Dendritic Cell Proliferation and Migration in Hepatic Allografts by Pretransplant Intraportal Infusion of Recipient Blood into Donor Rats

F.S. Wang, J.-l. Zhang, Z.G. Shao, Y.F. Liu — 2011-12-01

Abstract: Introduction: We have reported that recipient blood transfusion pretransplant prolongs hepatic allograft survival in rats. This study further investigated the mechanisms of the phenomenon. Materials and methods: Male LEW and ACI rats were used as liver transplant recipients and donors, respectively. Experimental animals were divided into control; treatment experimental; and intraportally transfused (1 mL recipient blood) at 7 days before transplantation. Results: Rat survival time was significantly longer among the experiment versus the control group. A large number of donor-source dendritic cells were detected among infiltrating cells in the liver and spleen in the experimental group. Conclusion: We concluded that the prolonged survival of hepatic allograft in these rats was associated with donor dendritic cell proliferation and migration.

Swine Dental Pulp Stem Cells Inhibit T-Cell Proliferation

R. Tang, G. Ding — 2011-12-01

Abstract: Dental pulp stem cells (DPSCs) hold great promise for tooth regeneration and dental diseases. To expand the source of DPSCs and explore the feasibility of allogeneic usefulness of DPSCs, we investigated its immunogenicity and its immunomodulatory effects on T lymphocytes. The results showed that DPSCs failed to stimulate allogeneic T-cell proliferation. In addition, they significantly inhibited phytohemagglutinin-triggered T-cell proliferation and one-way mixed lymphocytes reactions. Soluble factor(s) may play important role in the immunosuppressive process. DPSCs have low immunogenicity and immunomodulatory actions on T lymphocytes, which may expand the source of DPSCs and reinforce the therapeutic interest in DPSCs.

Inhibition of T-Cell Expansion Caused by Inducible Costimulator/B7h Costimulation Blockade in Direct Allorecognition Pathway

J.F. Du, Q.-Y. Li, X.Q. Ji, G. Chen, X. Bai, F.-Y. Zuo, B. Yu — 2011-12-01

Abstract: Objective: Inducible costimulator (ICOS)/B7h costimulation plays a crucial role in acute and chronic allograft rejection. To test the role of the ICOS signal in T-cell activation and expansion, we used ICOS-Fc–targeted B cells as donor antigen presenting cells to challenge the allogeneic response in vitro. Methods: In vitro, the binding of ICOS-Fc with B7h on splenic B cells was confirmed by flow cytometry analysis. To evaluate the capacity of ICOS-Fc–targeted B cells to elicit an allogeneic response in vitro, we performed mixed lymphocyte reactions. Results: The binding of B7h on splenic B cells by ICOS-Fc was confirmed at a saturating concentration of 100 μg/mL. Blockade of ICOS/B7h in direct allorecognition depressed proliferation of alloreactive T cells in vitro. Conclusions: ICOS/B7h signal plays an important role in direct allorecognition, eliciting allogeneic responses in vitro.

Anti-Gal Titers in Healthy Adults and Inflammatory Bowel Disease Patients

2011-12-01

Abstract: Introduction: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. Materials and methods: We drew serum from healthy probands (n = 20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n = 20) and ulcerative colitis (n = 20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. Results: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P < .01). Conclusion: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort.

Indoleamine 2,3-Dioxygenase as a Predictor of Acute Rejection After Orthotopic Liver Transplantation in Rat Model

M.-Z. Weng, Y.-G. Xu, Y. Zhang, J.-Y. Zhang, Z.-W. Quan, J.-M. Xu, Z.H. Peng — 2011-12-01

Abstract: Background: Indoleamine 2,3-dioxygenase (IDO) had been reported to correlate with immunomodulatory effects and the severity of acute rejection (AR) after liver transplantation. We sought to study the time course of IDO mRNA expression in peripheral blood to diagnose AR. Methods: The rats were divided into 4 groups each consisting of 32 rats: group A, isograft Sprague-Dawley (SD)–SD); group B, acute rejection model (SD-Wistar); group C, cyclosporine (CsA)–induced acceptance model (SD-Wistar rats treated with CsA, and group D, short-term CsA-treated model. The peripheral blood and liver tissue samples were obtained on the day of operation as well as 1, 2, 3, 4, 5, 7, and 9 days thereafter. We performed reverse-transcription polymerase chain reaction, pathologic studies, and serum tests. Results: Groups A and C showed low levels of IDO mRNA as well as normal values of aspartate transaminase (AST), total bilirubin (T-BIL), and alkaline phosphatase (ALP) without AR. Group B showed a dramatic rise in IDO mRNA on day 2 with increased AST, T-BIL, and ALP at day 4 and mild AR on day 5. Group D, showed dramatically up-regulated IDO mRNA on day 4 with significantly increased AST, T-BIL, and ALP day 5 and mild AR detected on day 7. The expression of IDO gene in peripheral blood tightly correlated with the severity of acute rejection (P < .001). Conclusions: Compared with the pathologic study detection of IDO mRNA in peripheral blood diagnosed AR in the rat model at an earlier stage.

Intestinal Microbiota and Innate Immunity-Related Gene Alteration in Cirrhotic Rats with Liver Transplantation

2011-12-01

Abstract: Background: The present study investigated the alteration of intestinal microbiota, innate immunity-related genes, and bacterial translocation in rats with cirrhosis and liver transplantation. Methods: Specific pathogen-free Sprague-Dawley rats were randomized into 4 groups: (1) normal controls (N); (2) liver cirrhosis (LC); (3) normal control groups with liver transplantation (LTN); and (4) liver cirrhosis with liver transplantation (LTC). We examined plasma endotoxin, bacterial tacslocation, Denaturing Gradient Gel Electrophoresis (DGGE) profile of intestinal mucosa-associated bacteria, abundance of key bacterial populations, and expression of innate immunity-related gene. Results: The LTC and LC group, showed higher endotoxin levels (1.08 ± 0.73 EU/mL and 0.74 ± 0.70 EU/mL, respectively) than the N group (0.27 ± 0.13 EU/mL; P < .05). the incidence of bacterial translocation (BT) to liver and mesenteric lymph nodes (MLN), and the number of total bacteria were increased significantly in the LTC and LC groups compared with the N group (P < .05). The counts of Lactobacilli and Bacteroides were lower, whereas Enterobacteria were higher in the LC than the N group (P < .05). Mucins (MUC2, MUC3) and Toll-like receptors (TLR2, TLR4) messenger RNA (mRNA) expression were significantly higher in the LC and LTC groups than the N group (P < .05). The marked difference between the groups in the overall structure of the bacterial community was also generated by DGGE profiles. Conclusion: Liver cirrhosis disturbs intestinal microbiota and innate immunity-related genes, which contributes to endotoxemia and bacterial translocation. These had not completely recovered in cirrhotic rats until 1 month after orthotopic liver transplantation.

Establishing a New Electrical Conduction Pathway by Anastomosis of the Right Auricle and Right Ventricle Assisted by Mesenchymal Stem Cells in a Canine Model

2011-12-01

Abstract: Background: Electronic pacemakers are the primary treatment of complete atrioventricular (AV) block, but their use is associated with many complications. The aim of the present study was to create an alternative treatment for these patients. Materials and Methods: Mesenchymal stem cells (MSCs) isolated from the bone marrow of a 3-month-old dog were cultured in vitro. The MSCs were labeled with 4′, 6-diamidino-2-phenylindole (DAPI) before transplantation. We anastomosed the right auricle and right ventricle in 24 dogs, and transplanted labelled MSCs into the anastomotic area of 8 dog hearts. Using immunostaining we assessed survival and differentiation of the implanted cells at 8 weeks posttransplantation. Electrocardiography confirmed the secondary electrical conduction pathway. Results: The ventricular current was captured by the electronic pacemaker in 21 dogs. Compared with the control group (surgery alone), pacemaker stimulus current was significantly less in the MSC group (surgery + MSCs). Conclusions: Anastomoşis of the right auricle and right ventricle assisted by MSCs may be a new treatment for patients with complete AV block in the future.

A Modified Rat Model of Acute Limb Allograft Rejection

Z. Zhang, H. Dong, L. Meng, Z. Chen, Y. Wu, R. Song, F. Li, Y. Feng, Z. Bi — 2011-12-01

Abstract: Background: The purpose of this study was to determine the feasibility of a simplified model of acute limb allograft rejection. Methods: Wistar rats were donors (n = 18), and Sprague-Dawley (SD) rats were recipients (n = 36). They were divided into a traditional and a modified model group. In the traditional group, the hind limb of the recipient was removed; blood vessels, bone, and nerve anastomoses were performed. In the modified group, the hind limb of the recipient was maintained while the allografted limb was transplanted near inside the original hind limb with only blood vessel anastomoses performed, and the donor limb was fixed in place by suturing muscle and skin. Results: The ischemic time of the donor limbs in the modified group was significantly less than the traditional group (67 ± 19.1 minutes vs 127 ± 15 minutes; P < .0001). In the traditional group, 12 models (66.7%) were successful and 6 failed, whereas in the modified group, 17 (94.4%) were successful and 1 failed (P = .087). Acute rejection occurred in all surviving rats; the time and characteristics of rejection were similar in the 2 groups. Conclusions: The simplified rat hind limb allotransplantation model described herein offers a greater success rate and shorter operative time than the traditional model while providing the same rejection characteristics.

Case Report: Successful Treatment of Recurrent Focal Segmental Glomerulosclerosis with a Novel Rituximab Regimen

Z.A. Stewart, R. Shetty, R. Nair, A.I. Reed, P.D. Brophy — 2011-12-01

Abstract: Focal segmental glomerulosclerosis (FSGS) is the cause of renal failure in more than 10% of pediatric patients undergoing renal transplantation. Recurrent FSGS is a major cause of pediatric allograft failure, with the risk increasing for patients undergoing retransplantation. Standard therapy for recurrent posttransplantation FSGS includes the use of intensive plasmapheresis (PP) in conjunction with cyclophosphamide or high-dose cyclosporine. However, many patients exhibit refractory disease, with rapid progression to allograft loss despite these interventions. Prior studies have reported conflicting data on the efficacy of adding rituximab therapy to the standard treatment regimen for recurrent posttransplantation FSGS. Here we present a successful therapeutic protocol with rapid elimination of PP after initiation of rituximab therapy for an adolescent patient with recurrent FSGS in the immediate postoperative period. The patient has maintained excellent allograft function through 12 months posttransplantation.

Percutaneous Ultrasound-Guided Radiofrequency Ablation of an Allograft Renal Cell Carcinoma: A Case Report

2011-12-01

Abstract: Background: Renal cell carcinomas (RCCs) are rarely described in transplanted kidneys. Available therapeutic strategies range from allograft nephrectomy to nephron-sparing procedures such as partial nephrectomy or image-guided thermal ablation. Percutaneous radiofrequency ablation (RFA) is a minimally invasive technique which provides promising oncologic outcomes in small allograft RCCs while preserving allograft function. So far, only a few cases have been reported in the transplant setting. We describe a renal transplant RCC successfully approached by ultrasound-guided RFA. Methods: A 42-year-old renal transplant recipient developed a small subcapsular allograft RCC at 11 years after transplantation. The decline in glomerular filtration rare prompted us to preserve as much parenchyma as possible. Ultrasound-guided RFA was performed under light sedation and local analgesia in a single session with a Starbust Talon needle. Results: Postablation contrast-enhanced ultrasound displayed a 25×23 mm avascular area of complete necrosis. After 3 months gadolinium-enhanced magnetic resonance imaging confirmed the absence of viable tumor tissue and while the patient did not experience any graft function reduction (serum creatinine 2.6 mg/dL). Conclusions: Image-guided RFA represents a promising therapeutic modality for small allograft RCCs in recipients with mild graft dysfunction and/or elevated surgical risk. It is associated with low morbidity and parenchymal preservation.

Late Presentation of Alport Posttransplantation Anti-Glomerular Basement Membrane Disease

2011-12-01

Abstract: We describe a female patient with Alport disease who developed antiglomerular basement membrane nephritis late after kidney transplantation during the treatment of an acute bacterial pyelonephritis and discuss the potential role of the infection as a trigger for the development of this nephritis.

Successful Use of the Dilated Right Spermatic Cord Vein for Renal Transplantation in a Patient with Congenital Hypoplasia of the Inferior Vena Cava

F.F. Guo, Z.Q. Shao, H.L. Li, G.J. Wang, W.B. Zhu — 2011-12-01

Abstract: A 29-year-old man was admitted to our department with renal failure secondary to glomerulonephritis. No history of deep venous thromboses was reported, and no iliac vessel abnormality was evident on routine ultrasound (B-mode) examination before the operation. Transplantation of his mother's left kidney revealed occlusion of his common iliac vein and distal inferior vena cava (IVC). The right spermatic cord vein was noted to be dilated and suitable for venous drainage of the allograft, which was accomplished by an end-to-side anastomosis between the renal vein and the right spermatic cord vein. The allograft showed immediate function; serum creatinine was decreased to a normal value at 5 days after surgery. After the operation, a vascular spiral computerized tomographic 3-dimensional reconstruction showed absence of the infrarenal IVC with the right spermatic cord vein draining into the end of IVC. Physical examination revealed a right-side varicocele with dilated epigastric vein. The donor kidney slower normal values upon routine follow-up at 2 years after the operation.

Recurrent Membranoproliferative Glomerulonephritis After Second Renal Graft Treated With Plasmapheresis and Rituximab

2011-12-01

Abstract: We present a case of a 45-year-old man who suffered from idiopatic membranoproliferative glomerulonephritis (MPGN) in the native kidney that relapsed after his first and second renal grafts. The patient was diagnosed in 1990 with lobular MPGN type I, receiving his first renal graft in 1996. In 2001, a biopsy showed recurrence of MPGN type I (rMPGN). He underwent a second renal graft in 2008. In January 2010, he experienced increased proteinuria and creatinine. Upon electron microscopy of a renal graft biopsy we diagnosed a new rMPGN. At the time of the biopsy, complement levels were normal, although C3 and C4 decreased further. We administered 12 plasmapheresis (PP) sessions and four doses of rituximab. Due to persistent renal impairment, we performed a new biopsy 3 months later, showing less severity of the acute lessions. He received a new cycle of treatment (PP + rituximab). One year later, his renal function was stable with a creatinine ranging between 2 and 2.5 mg/dL and a protein/creatinine ratio less than 1 mg/mg. We concluded that the treatment stopped the disease progression.

Diagnostic Challenges in the Evaluation of Hepatic Grafts From Donors With HELLP Syndrome: Case Report and Review of the Literature

W.H. Kitchens, A.B. Adams, C.B. Hughes, R.M. Subramanian — 2011-12-01

Abstract: HELLP syndrome (hemolysis, elevated liver function tests, low platelets) is a rare complication of pregnancy that can result in severe complications such as hepatic infarction, subcapsular liver hematomas, and maternal brain death from cerebral hemorrhage. Recently, several investigators have described cases of successful transplantation using livers procured from donors who suffered brain death as a result of HELLP syndrome. However, this new class of marginal liver donors must be approached with caution. We report the case of a 28-year-old pregnant woman who suffered brain death due to HELLP syndrome and was subsequently evaluated for potential liver donation. Although her transaminitis and other liver function tests were markedly improving during the final days of her hospital course, her liver demonstrated segments of necrosis during attempted procurement, and the histology revealed extensive centrilobular necrosis. This case suggests that peak values of serum transaminases, as well as partial resolution of transaminitis, appear to have limited predictive ability in determining the suitability of the hepatic graft for transplantation. Thus, donors with HELLP syndrome should be approached with caution, even in the setting of laboratory values suggesting minimal or resolving hepatic injury. Furthermore, there should be an additional emphasis on obtaining and reviewing histology of the potential graft to determine its suitability for transplantation.

Long-Term Survival After Living-Donor Liver Transplantation for Unresectable Colorectal Metastases to the Liver: Case Report

2011-12-01

Abstract: We present a case of long-term survival of a patient who underwent living-donor liver transplantation for unresectable liver metastases of colon cancer. Two years after left hemicolectomy and subsequent to repeated liver resections, this patient presented with unresectable metastatic disease confined to the liver. She was offered a living-donor liver transplantation, and her husband agreed to be the donor. Five years after transplant, she was alive and recurrence free.

Hyperkalemic Distal Renal Tubular Acidosis Caused by Immunosuppressant Treatment with Tacrolimus in a Liver Transplant Patient: Case Report

2011-12-01

Abstract: Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.

Hepatic Arterial Buffer Response after Pediatric Living Donor Liver Transplantation: Report of a Case

2011-12-01

Abstract: Background: Excessive portal pressure at an early stage after living-donor liver transplantation (LDLT) can damage sinusoidal endothelial cells and hepatocytes through shear stress leading to graft failure, or hepatic arterial complications due to low hepatic artery flow from a hepatic arterial buffer response. We encountered a case in which excessive portal vein flow was observed from an early stage after pediatric LDLT. The hepatic artery flow decreased due to a hepatic arterial buffer response. Case report: A 6-month-old boy with biliary atresia showed excessive portal vein flow early after LDLT with a decreasing hepatic artery flow without anastomotic stenosis from postoperative day 3. The PV flow gradually exhibited a decrease at approximately postoperative day 8 and, similtaneously, hepatic artery flow exhibited improvement. Conclusion: Because excessive portal pressure after LDLT is reversible, it has been suggested that it may be possible to prevent the progress of hepatic arterial complications if temporary portal pressure modulation can be performed for cases among the high-risk group for hepatic arterial complications.

Case Report of a Successful Liver Transplantation for Acute Liver Failure Due to Mitochondrial Respiratory Chain Complex III Deficiency

2011-12-01

Abstract: Mitochondrial respiratory chain disorders can cause acute liver failure in infants and children. Liver transplantation, however, has rarely been indicated for patients with mitochondrial respiratory chain disorders, because of the extrahepatic involvement. Herein we reported a case of acute liver failure with mitochondrial respiratory chain complex III deficiency treated by liver transplantation. At 2 years after transplantation, there were no extrahepatic manifestations. We suggest that mitochondrial disorders should be considered to be a cause of liver failure in infancy and that liver transplantation can be a life-saving treatment.

Ex Vivo Evaluation of Lungs from Donation after Cardiac Death after Recent Cardiac Surgery with Cardiopulmonary Bypass

B. Zych, A.F. Popov, A.R. Simon, M. Carby, K. Redmond — 2011-12-01

Abstract: Lack of suitable donor lungs is still a major limitation of lung transplantation. Extended donor acceptance criteria combined with innovative assessment tools can be used to expand the number of suitable organs. We describe a successful transplantation of lungs retrieved from a donor who had undergone aortic root replacement 9 days before donation after cardiac death. The lungs were assessed using ex-vivo lung perfusion.

Transfer of Peanut Allergy Following Lung Transplantation: A Case Report

2011-12-01

Abstract: This case study describes a patient who developed peanut allergy following lung transplantation. A 54-year-old woman underwent bilateral lung transplantation on June 2009 owing to severe chronic obstructive pulmonary disease. She had no history of food allergy before transplantation. The donor, however, was a 20-year-old man who was fatally injured during an automobile accident; he was allergic to peanuts. At 3 months after transplantation, the lung recipient presented with acute dyspnea and urticaria 15 minutes after consuming food containing peanut derivatives. Pre- and posttransplantation recipient blood samples analyzed for the presence of IgE antibodies specific for peanut allergens confirmed that the allergy had been passively transfered as a consequence of transplantation. Food allergy following solid organ transplantation is thought to be rare, mostly occurring in children. Two mechanisms may explain the observations described for the patient reported in this study: de novo development of peanut allergies after transplantation, or passive transfer of peanut allergies from a peanut-sensitized organ donor. This case report documenting pre- and posttransplantation IgE status in a lung transplantation case suggested that the allergic status of organ donors should be thoroughly assessed before transplantation, and potential allergy transfer risks must be discussed with the transplant team and the patient.

Pulmonary Resection for Airway Complication After Lung Transplantation in a Patient with Cystic Fibrosis: A Case Report

2011-12-01

Abstract: We report a case of the interdisciplinary management of recurring bronchial stenosis after bilateral sequential single-lung transplantation (BSSLT) in a 35-year-old female with cystic fibrosis. Initial bronchoscopic therapy including balloon dilatation, stenting, and cryotherapy for granulation tissue overgrowth was unsuccessful in maintaining airway patency. In view of the persistent left lower lobe (LLL) atelectasis and fibrosis predisposing to recurrent infections, she was submitted for left lower lobectomy.

Case Report: Gastrointestinal Hemorrhage Caused by a Pancreas Transplant Arteriovenous Fistula with Large Psuedoanuerysm 9 Years after Transplantation

C.F. Bratton, A. Hamid, J.B. Selby, P.K. Baliga — 2011-12-01

Abstract: Reported cases of arteriovenous fistulae in transplant recipients are uncommon. We present a case of an arteriovenous fistula associated with a large pseudoaneurysm in the root of the small bowel mesentery of a pancreas transplant. Uniquely, in our case, the arteriovenous fistula presented with an episode of gastrointestinal (GI) hemorrhage 9 years postoperatively. Radiographic imaging including coronal computed tomography angiogram and conventional angiogram demonstrated an arteriovenous fistula in the patient's pancreas transplant between the distal superior mesenteric artery (SMA) and superior mesenteric vein (SMV) with 6 cm aneurysmal dilatation. The tremendous flow in the fistula in the root of the graft small intestine mesentery led to graft duodenal mucosal congestion and lower GI hemorrhage. After successful embolization of the SMA–SMV fistula and pseudoaneurysm using interventional radiographic techniques, the arteriovenous fistula remained thrombosed. The patient had no further episodes of GI bleeding and her endoscopic evaluation was otherwise negative. The presence of arteriovenous fistulae and pseudoaneurysms in pancreas transplant recipients is uncommon, but has been previously documented. This case is further distinguished from previous reports by the notable 9-year interval between transplantation and the onset of hemorrhage. Historically, symptomatic vascular malformations have been associated with significant patient morbidity and mortality. Successful patient management involves timely and accurate diagnosis and intervention.

Embolization of Pancreatic Allograft Arteriovenous Fistula with the Amplatzer Vascular Plug 4: Case Report and Literature Analysis

L. Buttarelli, E. Capocasale, C. Marcato, M.P. Mazzoni, M. Iaria, C. Rossi — 2011-12-01

Abstract: Vascular complications remain a major cause of graft loss after pancreatic transplantation. They include vascular thrombosis, pseudoaneurysm, and arteriovenous fistula (AVF). We report a case of an AVF that appeared 3 months after a simultaneous pancreas-kidney transplantation (SPKT). Doppler ultrasonography followed by magnetic resonance angiography and later angiography provided a definitive diagnosis of a mesenteric AVF. An endovascular approach is becoming the treatment of choice owing to the high risk of graft loss associated with open surgical correction. Microcoils alone, or in conjunction with detachable balloons, are frequently used; still, a new generation of vascular plugs seem to offer a therapeutic option for AVF closure, because it is a “1 shot” procedure that avoids the risk of accidental coil migration. A new-generation Amplatzer Vascular Plug 4 was deployed over the distal arterial branch of the superior mesenteric artery stump, leading to complete exclusion of the AVF and restoring normal vascular flow.

Author Index

2011-12-01

Transplantation Proceedings

Editorial Board

Contents

Repairing the Chronic Damaged Kidney: The Role of Regenerative Medicine

Oxidative Stress and Renal Interstitial Fibrosis in Patients After Renal Transplantation: Current State of Knowledge

Living-Donor Liver Transplantation: Impact on Donor's Health-Related Quality of Life

Is Single-Shot Epidural Analgesia More Effective Than Morphine Patient-Controlled Analgesia for Donor Nephrectomy?

Laparoscopic Live-Donor Nephrectomy: A Comparison with the Open Technique and How to Reach Quality Standards: A Single-Center Experience in Thailand

Public Opinion on Renal Transplantation in Brunei Darussalam

Effects of n-3 Polyunsaturated Fatty Acids on Rat Livers after Partial Hepatectomy via LKB1-AMPK Signaling Pathway

Potential Protective Effect of Nuclear Factor-κB Decoy Oligodeoxynucleotides on Endotoxin-induced Liver Injury

Erythropoietin Attenuates Apoptosis After Ischemia-Reperfusion–Induced Renal Injury in Transiently Hyperglycemic Wister Rats

Protective Effects of Neutrophil Gelatinase–Associated Lipocalin on Hypoxia/Reoxygenation Injury of HK-2 Cells

Activations of Mitogen-Activated Protein Kinases and Regulation of Their Downstream Molecules After Rat Lung Transplantation from Donors After Cardiac Death

Relationship Between Ischemia/Reperfusion Injury and the Stimulus of Fibrogenesis in an Experimental Model: Comparison Among Different Preservation Solutions

Acceptable Warm Ischemia Time of Tracheal Grafts From Non–heart-beating Donors in Rats

Effect of Methylene Blue on the Hemodynamic Instability Resulting From Liver Ischemia and Reperfusion in Rabbits

Impact of Pre-Existing Left Ventricular Dysfunction on Kidney Transplantation Outcomes: Implications for Patient Selection

Better Actual 10-Year Renal Transplant Outcomes of 80% Reduced Cyclosporine Exposure With Sirolimus Base Therapy Compared With Full Cyclosporine Exposure Without or With Concomittant Sirolimus Treatment

Sequential Monitoring of TIM-3 Gene Expression in Peripheral Blood for Diagnostic and Prognostic Evaluation of Acute Rejection in Renal Graft Recipients

Lymphocyte ATP Immune Cell Function Assay in Pediatric Renal Transplants: Is It Useful?

The Utility of Cytodiagnostic Urinalysis as a Tool to Diagnose Kidney Allograft Dysfunction in the Era Lymphocyte-Depleting Induction Therapy

Outcome of Kidney Transplantation From Elderly Donors After Cardiac Death

Factors of Impact on Graft Function at 2 Years After Transplantation in Living-Donor Kidney Transplantation: A Single-Center Study in China

Changes of Progesterone-Induced Blocking Factor in Patients After Kidney Transplantation

Efficacy and Safety of Changing From Cyclosporine C0 to C2 Monitoring in Stable Recipients Following Renal Transplantation: A Prospective Cohort Study

Impact of the Conversion of the Immunosuppressive Regimen from Prograf to Advagraf or to Sirolimus in Long-term Stable Liver Transplant Recipients: Indications, Safety, and Outcome

Tacrolimus Pharmacokinetics in Hispanic Children After Kidney Transplantation

Preemptive Kidney Transplantation in Systemic Lupus Erythematosus

Opportunistic Posttransplantation Virus Infections in Renal Transplant Recipients

The Seroprevalence of Helicobacter pylori Infection in Renal Transplant Recipients

Impact of Vitamin D on Proteinuria, Insulin Resistance, and Cardiovascular Parameters in Kidney Transplant Recipients

Lipid Profile Changes During the First Year After Kidney Transplantation: Risk Factors and Influence of the Immunosuppressive Drug Regimen

Urinary Metabolomics in Monitoring Acute Tubular Injury of Renal Allografts: A Preliminary Report

Patterns of IgG Subclass Deposits in Membranous Glomerulonephritis in Renal Allografts

Routine Short-Term Ureteral Stent in Living Donor Renal Transplantation: Introduction of a Simple Stent Removal Technique Without Using Anesthesia and Cystoscope

Association Between Urothelial Carcinoma After Kidney Transplantation and Aristolochic Acid Exposure: The Potential Role of Aristolochic Acid in HRas and TP53 Gene Mutations

Does Ultrasonic Energy for Surgical Dissection Reduce the Incidence of Renal Transplant Lymphocele?

Skin Cancer Following Kidney Transplantation: A Single-Center Experience

Orthotopic Liver Transplantation in Critically Ill Cirrhotic Patients With Multi-Organ Failure: A Single-Center Experience

Social Determinants of Orthotopic Liver Transplantation Candidacy: Role of Patient-Related Factors

Right Lobe Living-Donor Liver Transplantation With or Without Middle Hepatic Vein: A Meta-Analysis

Orthotopic Liver Transplantation in a Multiethnic Population: Role of Spatial Accessibility

Cost Analysis of Liver Transplantation in Turkey

Donor Age Does Not Influence 12-Month Outcome After Orthotopic Liver Transplantation

International Collaboration of Turkey in Liver Transplantation Research: A Bibliometric Analysis

Long-Term Outcomes of Calcineurin Inhibitor Withdrawal for Post–Liver Transplant Renal Dysfunction

Effects of Risk Factors and Ki-67 on Rates of Recurrence on Patients Who Have Undergone Liver Transplant for Hepatocellular Carcinoma

Rate of Tumor Growth Predicts Recurrence of Hepatocellular Carcinoma After Liver Transplantation in Patients Beyond Milan or UCSF Criteria

Liver Graft Failure and Hyperbilirubinemia in Liver Transplantation Recipients After Clostridium difficile Infection

The Effect and Safety of the Treatment of Recurrent Hepatitis C Infection After Orthotopic Liver Transplantation With Pegylated Interferon α2b and Ribavirin

Portal Vein Stenosis: A Rare Yet Clinically Important Cause of Delayed-onset Ascites after Adult Deceased Donor Liver Transplantation: Two Case Reports

Factors Influencing Posttransplantation Employment: Does Depression Have an Impact?

Effect of Pretransplant Human Leukocyte Antigen Antibodies Detected by Solid-Phase Assay on Heart Transplant Outcomes

Comparison of Heart Transplantation Patients with Ischemic and Idiopathic Dilated Cardiomyopathy

Heart Transplantation in Patients Aged 70 Years and Older: A Two-Decade Experience

Exercise Performance Comparison of Bicaval and Biatrial Orthotopic Heart Transplant Recipients

Prolonged Cold Ischemic Times and Less Donor-Recipient Histocompatibility Accelerate Graft Vascular Disease

Survival and Allograft Rejection Rates after Combined Heart and Kidney Transplantation in Comparison with Heart Transplantation Alone

Noninvasive Diagnosis of Cardiac Allograft Rejection Using Echocardiography Indices of Systolic and Diastolic Function

Successful Use of the TandemHeart Percutaneous Ventricular Assist Device as a Bridge to Recovery for Acute Cellular Rejection in a Cardiac Transplant Patient

Prevalence of Iron Deficiency in Heart and Kidney Allograft Recipients

Serum Renalase Depends on Kidney Function But Not on Blood Pressure in Heart Transplant Recipients

Cumulative Exposure to CD8+ Granzyme Bhi T Cells Is Associated with Reduced Lung Function Early after Lung Transplantation

Influence of Gender Donor-Recipient Combinations on Survival After Human Lung Transplantation

Simultaneous Pancreas Kidney Transplantation in the HIV-Positive Patient

Gastroduodenal Arterial Reconstruction of the Pancreaticoduodenal Allograft

Effects of Astragalosides on Cultured Islets After Cryopreservation in Rats

High Expression of Fas Ligand on Cord Blood Dendritic Cells: A Possible Immunoregulatory Mechanism After Cord Blood Transplantation

Imbalance Between Bone Formation and Resorption in Hematopoietic Stem/Progenitor Cells Mobilization

Immunoglobulin Prophylaxis Against Cytomegalovirus Infection in Patients at High Risk of Infection Following Allogeneic Hematopoietic Cell Transplantation

Galectin-3 Enhances Proliferation and Angiogenesis of Endothelial Cells Differentiated from Bone Marrow Mesenchymal Stem Cells

Oxidative Stress Indices in Rats Under Immunosuppression

Donor Dendritic Cell Proliferation and Migration in Hepatic Allografts by Pretransplant Intraportal Infusion of Recipient Blood into Donor Rats

Swine Dental Pulp Stem Cells Inhibit T-Cell Proliferation

Inhibition of T-Cell Expansion Caused by Inducible Costimulator/B7h Costimulation Blockade in Direct Allorecognition Pathway

Anti-Gal Titers in Healthy Adults and Inflammatory Bowel Disease Patients

Indoleamine 2,3-Dioxygenase as a Predictor of Acute Rejection After Orthotopic Liver Transplantation in Rat Model

Intestinal Microbiota and Innate Immunity-Related Gene Alteration in Cirrhotic Rats with Liver Transplantation

Establishing a New Electrical Conduction Pathway by Anastomosis of the Right Auricle and Right Ventricle Assisted by Mesenchymal Stem Cells in a Canine Model