Operational Tolerance in Living-Related Renal Transplantation: A Single-Center Experience

Abstract

Introduction Various methods have been tried to induce operational tolerance in organ transplantation. We present a single-center experience using 6 tolerance induction protocols (TIP) in living-related renal transplantation. Methods We evaluated 6 TIP protocols: (1) peripheral blood stem cells employed ( n = 38); (2) midified the protocol by portal infusion ( n = 292); (3) the second protocol plus TIP+DST+BM+intrathymic and intramarrow infusion plus low-dose, nonmyeloablative conditioning employed ( n = 174), (4) the third protocol of TIP plus cultured hematopoietic stem cells (HSC) with target-specific irradiation ( n = 290); (5) TIP 4 plus thymus, intramarrow infusion, and target-specific irradiation converted to total lymphoid irradiation (TLI) ( n = 366); and (6) TIP 5 plus bortzomib–TLI ( n = 165). Patient/donor demographics were comparable. Results We evaluated patient and graft survival, rejection episodes, recurrence, drug toxicity, and chimerism revealed; groups 4 and 5 showed better survival, graft function, chimerism, and decreased rejection episodes compared with previous protocols. Serum creatinine (mg/dL) at 1 year was 1.5, 1.39, 1.5, 1.51, 1.46, and 1.41, and at 5 years, 1.69, 1.72, 1.82 and 1.59, in groups 1–6, respectively. Chronic rejection episodes were 10.5%, 14.1%, 10.4%, 9.3%, 3.5%, 1.7%, and 1.8% respectively. Patient survival of groups 1, 2, and 3 at 1, 5, and 10 years was 86.5%, 56.8%, and 40.1%; 89.4%, 69.1%, and 56.4%; and 89.6%, 67.7%, and 64.6%, respectively; of group 4 for 1 and 5 years was 92.4% and 81.8%; for groups 5 and 6 for 1 year was 94% and 96.3%, respectively. The death-censored graft survival of groups 1, 2, and 3 at 1, 5, and 10 years was 91.9%, 70.3%, and 64.7%; 89%, 66%, and 57.6%; and 86.7%, 67%, and 42.5%, respectively. In group 4 for 1 and 5 years was 87.9% and 74.7%; and for groups 5 and 6 for 1 year was 94% and 96.5%, respectively. Conclusion TIP results showed improved graft/patient survivals, minimum immunosuppression, and fewer rejection episodes and recurrence.