Effect of long-term tacrolimus immunosuppression on renal function in liver transplant recipients

Study Objectives. To describe changes in renal function occurring after long-term treatment with tacrolimus in clinically stable liver transplant recipients, and to identify risk factors for a clinically significant decline in renal function in these patients. Design. Retrospective cohort study Setting. University medical center. Patients. Four hundred thirty-two patients aged 18 years or older who underwent liver transplantation between January 1, 1996, and December 31, 2000, and received tacrolimus as part of their immunosuppressive treatment regimen. Measurements and Main Results. Six hundred patients were identified from an electronic records review. Those who received multiorgan transplants, were not receiving their first liver transplant, or died during the hospitalization were excluded from the study. Outcomes measured were change in mean glomerular filtration rate (GFR) up to 5 years after transplantation, and proportion of patients with a decline in GFR of 30% or greater from baseline to the last recorded serum creatinine level. Covariates that affected this decline were identified using a logistic regression model. Patients were followed for a mean +/- SD of 3.7 +/- 2.0 years. Mean GFR showed a statistically significant decline from baseline to end of follow-up (67.7 +/- 25.6 vs 58.4 +/- 26.5 ml/min/1.73 m(2), p < 0.001). The GFR declined by 30% or more in 154 (35.6%) patients. Increasing age (odds ratio [OR] = 1.03, p=0.00), female sex (OR = 1.92, p=0.006), higher baseline GFR (OR = 1.03, p < 0.001), and diagnosis of diabetes mellitus (OR = 1.74, p=0.059) were identified as predictors of this outcome. Conclusion. After the acute posttransplantation period, liver transplant recipients given long-term treatment with tacrolimus experienced only small changes in GFR over time. Patients with diabetes and women had the highest risk of experiencing a clinically significant decline in renal function.