ObjectiveIn this first report of a clinical series of simultaneous pancreas-kidney transplants (SPKs) from live donors, the authors assess donor and recipient outcome as well as the spectrum of surgical and metabolic complications. Summary Background DataThe rationale for live (vs. cadaveric) donation includes an immunologic advantage (better matching, decreased drugs, and fewer rejection episodes) and elimination of waiting time. Only sequential kidney and pancreas or pancreas transplants alone from live donors had been done until the authors' current series. MethodsBetween March 15, 1994, and March 15, 1997, the authors performed 20 SPKs from live donors (6 human leukocyte antigen-identical siblings, 14 mismatched relatives [5 parents, 7 siblings, 1 daughter, 1 aunt]). Of the 20 donors, 13 were women, and 7 were men; median age was 43 years (range, 30-58 years). All donors underwent standardized metabolic workup, including oral glucose tolerance tests, determination of hemoglobin Al c levels, and tests to study insulin secretion and functional insulin secretory reserve. Of the 20 recipients, 12 were women, and 8 were men; median age was 34 years (range, 14-50 years). Management of exocrine pancreatic secretions was with bladder drainage in 17 and duct injection in 3 recipients. Median follow-up was 9 months (range, 1-36 months). ResultsCurrently, all 20 kidney grafts are functioning. Of the 20 pancreas grafts, 15 are functioning, 3 thrombosed, but 2 of those patients underwent immediate retransplantation from a cadaveric donor, and their grafts currently are functioning. Recipient complications included three anastomotic leaks and three intra-abdominal abscesses. Donor complications included four splenectomies, two peripancreatic fluid collections, one pseudocyst, and one intra-abdominal abscess; two donors underwent reoperation. Three donors had impaired glucose metabolism postdonation. Using tacrolimus and mycophenolate mofetil for mainstay immunosuppression, only 8 of 20 recipients experienced .1 rejection episode; only 1 pancreas graft was lost to rejection. Donor and recipient mortality was 0%. ConclusionSimultaneous pancreas-kidney transplants from live donors can be done with no mortality and good graft outcome. With stringent donor criteria, this approach could become 471
Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n = 82), (2) recipients switched to FK506 for antirejection or rescue therapy (n = 61), and (3) recipients converted to FK506 for other reasons (n = 11). Of 82 patients in the induction group, 7 (9%) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66%) had SPK transplants without BM, 14 (17%) had pancreas transplants alone (PTA), and 7 (9%) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16%), nephrotoxicity (13%), and gastrointestinal toxicity (9%). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72%) were SPK, 11 (18%) PTA, and 6 (10%) PAK. All but 3 (95%) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46% of the recipients had one, and 54% > or = 2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25%), neurotoxicity (23%), and gastrointestinal toxicity (21%). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90% for SPK, 100% for PTA, and 100% for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87% for FK506 versus 70% for cyclosporine recipients (P = 0.04); for PTA recipients, 84% versus 66% (P = n.s.); and for PAK recipients, 80% versus 14% (P = 0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35% for SPK, 40% for PTA, and 20% for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV-positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91% for SPK, 100% for PTA, and 80% for PAK (P = n.s.). Pancreas graft survival rates at 6 months were 90% for SPK, 72% for PTA, and 40% for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44% in SPK, 54% in PTA, and 50% in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with ...
The combination of MMF and tacrolimus after pancreas transplantation is highly effective and safe. For SPK recipients, the incidence of acute reversible rejection episodes was significantly lower with MMF than with azathioprine. The conversion rate from MMF to azathioprine because of GI toxicity was lowest for SPK and highest for PTA recipients.
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