Elsevier

Transplantation Proceedings

Volume 47, Issue 10, December 2015, Pages 2968-2972
Transplantation Proceedings

Transplantation in the Twenty-First Century
General clinical transplantation
Race, Calcineurin Inhibitor Exposure, and Renal Function After Solid Organ Transplantation

https://doi.org/10.1016/j.transproceed.2015.10.052Get rights and content

Highlights

  • Total calcineurin-inhibitor exposure is associated with eGFR decline.

  • African-American patients are not more vulnerable to chronic calcineurin-inhibitor induced nephrotoxicity when compared to white patients.

Abstract

Background

Calcineurin-inhibitor (CNI)–induced nephrotoxicity frequently complicates transplantation. African-Americans are at a greater risk of renal failure than the general population. We investigated whether race was an effect modifier of the relationship between CNI exposure and kidney function after nonrenal solid organ transplantation.

Methods

This is a retrospective cohort study of 1609 patients who underwent initial nonrenal solid organ transplantation between January 2000 and June 2012. A central repository administrative database was queried electronically for demographics, comorbidities, and serial levels of tacrolimus, cyclosporine, and serum creatinine. Predictors of interest were total drug exposure of tacrolimus and cyclosporine (area under the concentration–time curve) and self-reported race. The outcome of interest was cumulative change in estimated glomerular filtration rate (GFR).

Results

There were 1109 patients treated with tacrolimus (271 African-Americans) and 500 patients treated with cyclosporine (113 African Americans). A decline in GFR over time was seen with total tacrolimus exposure (−1.3 mL/min/1.73 m2 for every 5 ng/mL·year increase in tacrolimus) and total cyclosporine exposure (−1.1 mL/min/1.73 m2 for every 50 ng/mL·year increase in cyclosporine). However, total CNI exposure effect on estimated GFR changes did not vary by race (P interaction was 0.9 for tacrolimus and 0.6 for cyclosporine).

Conclusions

Total CNI exposure is associated with worsening kidney function among patients with nonrenal solid organ transplantation. However, African-American patients are not more vulnerable to chronic CNI-induced nephrotoxicity when compared to white patients.

Section snippets

Study Population and Participants

We conducted a retrospective cohort study utilizing an administrative-linked electronic database of patients in the Henry Ford Health System in Michigan. The system includes several hospitals, a multispecialty physician group of approximately 1000 physicians, and an affiliated health maintenance organization. The system maintains a central repository of administrative data that we queried for this study. Using electronic data sources, we identified 1609 patients 18 years of age or older who

Results

Of the 1609 patients identified, 1109 patients were treated with tacrolimus (271 African-Americans) and 500 were treated with cyclosporine (113 African-Americans) (Fig 1). Demographics and baseline characteristics stratified by race are shown in Table 1. History of hypertension was more prevalent in African-Americans than whites. African-Americans were younger, had a higher proportion of females, and slightly higher eGFRs than whites. Multivariate modeling adjusted for age, gender,

Discussion

The introduction of CNIs has revolutionized transplantation medicine. They are now widely used as immunosuppressant therapy for liver, renal, cardiac, and lung transplantation. Patients treated with the CNIs cyclosporine and tacrolimus are at a high risk of developing renal injury [20]. Nephrotoxicity can be divided into acute and chronic forms. Acute nephrotoxicity is primarily associated with profound alterations in vascular flow [21], [22], [23] and vasoconstriction of preglomerular afferent

Acknowledgments

The authors express their gratitude to Stephanie Stephens for expert librarian assistance in formatting the manuscript and for expert linguistic revision of the manuscript.

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