Race, Calcineurin Inhibitor Exposure, and Renal Function After Solid Organ Transplantation
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 m(2) for every 5 ng/mL·year increase in tacrolimus) and total cyclosporine exposure (-1.1 mL/min/1.73 m(2) 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.
Medical Subject Headings
Calcineurin Inhibitors; Continental Population Groups; Cyclosporine; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Humans; Incidence; Kidney Function Tests; Male; Middle Aged; Organ Transplantation; Renal Insufficiency; Retrospective Studies; Survival Rate; Tacrolimus; United States