ABSTRACT
The aim of this study was to evaluate long-term outcome of sirolimus (SRL) rescue in kidney-pancreas transplantation (KPTx). We reviewed 112 KPTx performed at our institution from 12/3/95 to 6/27/02. All patients received antibody (Ab) induction, tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. Thirty-five patients (31%) had SRL substituted for MMF for the following indications: (1) acute rejection (AR) of kidney or pancreas despite adequate TAC levels; (2) intolerance of full-dose MMF; (3) rising creatinine; and (4) TAC-induced hyperglycemia. Target SRL and TAC levels were 10 ng/mL and 5 ng/mL, respectively. Mean follow-up was 3 +/- 2 years overall and 1.2 +/- 0.5 years after SRL rescue. No patients died. One- and 3-year actuarial kidney and pancreas graft survival was 97%, 97%, and 95%, 90%, respectively. Of 10 patients switched to SRL for AR, 1 kidney failed from Ab-resistant AR, 1 kidney developed borderline AR, and the other 8 remain AR-free. Seven other patients developed AR despite therapeutic SRL levels; of these, 6 (86%) had mean TAC levels of <4.5 in the month preceding AR. Mean creatinine overall and for the rising creatinine group remained stable. All patients switched to SRL for TAC-induced hyperglycemia or MMF intolerance demonstrated biochemical or clinical improvement. Sirolimus-related infection or other serious adverse events (SAE) were uncommon. In conclusion, KPTx recipients can be safely switched to SRL with long-term stabilization of renal function, excellent graft and patient survival, and no increase in SAE. A minimum TAC level of 4.5 ng/mL may be necessary to prevent late AR.
Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Mycophenolic Acid/analogs & derivatives , Pancreas Transplantation/immunology , Sirolimus/therapeutic use , Creatinine/blood , Follow-Up Studies , Humans , Kidney Transplantation/methods , Kidney Transplantation/physiology , Mycophenolic Acid/therapeutic use , Pancreas Transplantation/methods , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
The renal transplant program at the MUSC was established in 1968 and is the only transplant center in South Carolina. It serves a large population of African American patients who constitute nearly two-thirds of the waiting list and more than half of all renal transplants. Between 1968-2000, 969 transplants were performed in 906 AA patients. Most received organs from cadaveric donors, while only 99 (10%) of AA patients received living donor transplants. The acceptance of living unrelated donors and the use of laparoscopic nephrectomy have had a negligible impact on living donations in this racial group. Primary disease had little effect on outcome except in diabetics whose mortality was higher. The one-year graft survival rates improved dramatically with the aggressive use of CsA without the use of antibody induction. The overall one- and 5-year graft survival rates improved from 53% and 32%, respectively, in the 1978-1983 era to 87% and 59%, respectively, in the 1993-2001 era. At MUSC, the emphasis has been on reducing mortality due to sepsis by limiting the number of rejections treated particularly in recipients of cadaveric organs. While this has resulted in reduced overall early mortality, it has not adversely affected graft survival. Our experience suggests that while short-term graft survival has improved significantly over the years for AA patients, the long-term outcome still remains relatively unchanged.