Better Actual 10-Year Renal Transplant Outcomes of 80% Reduced Cyclosporine Exposure With Sirolimus Base Therapy Compared With Full Cyclosporine Exposure Without or With Concomittant Sirolimus Treatment

Objective. Retrospective analysis of 10-year outcomes of sirolimus (SRL) plus varying exposure to cyclosporine (CsA) in combination therapy for renal transplantation. Methods. Univariate, multivariate, and receiver operating characteristic (ROC) analyses of 10-year outcomes of 167 subjects treated with full exposures to CsA/SRL/steroid versus 233 with CsA/no SRL/steroid who were generally enrolled in randomized trials versus 192 patients prescribed 80% reduced CsA exposure adjunctive to SRL baseline therapy with steroid withdrawal (groups 1, 2, and 3, respectively). Results. Groups 1 and 3 showed greater 1-year graft survivals (GS) than group 2 (93% and 94% vs 86%; P=.05, particularly when mean SRL C-0 >= 10.5; P=.02); fewer acute rejection episodes (11% and 19% vs 40%; P<.001) and more frequent success of steroid withdrawal (47% and 66% vs 27%; P<.0001). Group 3 versus 1 displayed a higher mean glomerular filtration rate using the Modification of Diet in Renal Disease (MDRD) formula: 56 versus 49 (P=.02) and 53 versus 41 mL/min per 1.73 m(2) (P<.001) at 5 and 10 years, respectively. The 10-year GS among group 1 subjects was predicted by a >= 59 mL/min per 1.73m(2) at 1 year using ROC. Multivariate analysis showed factors predictive of 10-year GS among group 1 to include living donor source (P=.004), younger recipient age (P=.02), and fewer HLA-mismatches (P=.02). For group 3, the adverse factors were lower MDRD (P=.01); hypercholesterolemia (P=.01), and advanced donor age (P=.02). Group 3 versus 1 subjects displayed fewer skin tumors (2.6% vs 7.1%; P=.04), sepsis bouts (3.6% vs 9%; P=.04), and herpes virus infection (10% vs. 23%; P=.002), but more urinary tract infections (64% vs 53%; P=.04) and wound problems (43.7% vs 25.1%; P<.0001). Conclusion. An 80% reduction of de novo CsA exposure in combination with SRL engendered improved renal function as well as better graft survival at 10 years compared with patients treated with full CsA exposures with or without SRL co-therapy.