National Variation in Use of Immunosuppression for Kidney Transplantation: A Call for Evidence-Based Regimen Selection

Abstract

Immunosuppression management in kidney transplantation has evolved to include an increasingly diverse choice of medications. Although informed by patient and donor characteristics, choice of immunosuppression regimen varies widely across transplant programs. Using a novel database integrating national transplant registry and pharmacy fill records, immunosuppression use at 6-12 and 12-24 mo after transplant was evaluated for 22 453 patients transplanted in 249 U.S. programs in 2005-2010. Use of triple immunosuppression comprising tacrolimus, mycophenolic acid or azathioprine, and steroids varied widely (0-100% of patients per program), as did use of steroid-sparing regimens (0-77%), sirolimus-based regimens (0-100%) and cyclosporine-based regimens (0-78%). Use of triple therapy was more common in highly sensitized patients, women and recipients with dialysis duration >5 years. Sirolimus use appeared to diminish over the study period. Patient and donor characteristics explained only a limited amount of the observed variation in regimen use, whereas center choice explained 30-46% of the use of non-triple-therapy immunosuppression. The majority of patients who received triple-therapy (79%), cyclosporine-based (87.6%) and sirolimus-based (84.3%) regimens continued them in the second year after transplant. This population-based study of immunosuppression practice demonstrates substantial variation in center practice beyond that explained by differences in patient and donor characteristics.

Keywords: clinical research/practice; health services and outcomes research; immunosuppressant; immunosuppressive regimens; kidney transplantation/nephrology; maintenance; steroid.

Figure 1. Proportion of patients receiving one of six mutually exclusive immunosuppression regimens during months 6–12 post-transplant

Each horizontal bar represents an individual center within US regions ordered by the proportion of patients that received triple ISx (Tac + MPA/AZA + Pred—shown in orange). Overall percentage of regimen use at patient-level across centers: Tac+MPA/AZA+Pred, 33.8%; Tac+MPA/AZA (No Pred), 25.8%; Tac without MPA/AZA, 11.3%; SRL-based, 9.9%; CSA-based, 7.8%; and other regimens, 11.6%. CSA, Cyclosporine; ISx, immunosuppression; MPA/AZA, mycophenolate acid; Pred, prednisone; Tac, tacrolimus.

Figure 2. Empirical Bayes Estimates for likelihood of regimen use compared with reference regimen

Red bar demonstrates national average rate of use of each regimen (within pair-wise regimen comparisons). Each red dot represents adjusted use at one center and the blue bars reflect 95% confidence intervals (CI) for use at the center determined by Empirical Bayes Estimates, adjusting for case factors of recipients at the center; exclusion of the national average by a 95% CI reflects adjusted center use significantly above or below the national average.