Variability of cyclosporine exposure and its relevance to chronic allograft nephropathy: a case-control study.

Abstract

Population data indicate that cyclosporine (CsA)-based immunosuppression has had relatively little effect on late renal allograft loss. For individual patients, however, the degree and variability of CsA exposure may be of prognostic importance. This case-control study has examined the contribution of these and other factors to the development of chronic allograft nephropathy (CAN) in patients receiving follow-up care in our unit. The electronic record was interrogated to identify adult, CsA-treated renal transplant recipients with CAN (group A) and CsA-treated controls with stable graft function for a minimum of 4 years posttransplantation and serum creatinine less than 200 micromol/L (group B). Age at transplantation, gender, years posttransplantation, donor source and age, kidney preservation time, human leukocyte antigen match, occurrence of delayed graft function, immunosuppressive regimen, weight-adjusted maintenance CsA dose, and coefficient of variation (CvarC0 ) of dose-adjusted CsA trough blood levels (C0/dose) were recorded (CvarC0 =[SD (C0/dose)/mean (C0/dose)]x100). Statistical analysis included binary logistic regression analysis. Three transplant recipients were excluded because of known noncompliance with immunosuppressive medication, leaving a study population of 102 patients. Recipient age (A<B, <0.001), CvarC0 (A>B, <0.01) and CsA dose (A>B, <0.02) were significantly different by univariate analysis. Only low recipient age ( P<0.001) and high CvarC0 ( P<0.02) were independent predictors of CAN in the regression model. Younger renal transplant recipients and those with highly variable CsA exposure are predisposed to developing CAN. Investigation of such patients may reveal correctable factors such as poor treatment compliance and lead to appropriate interventions.