Solitary pancreas transplantation for nonuremic patients with labile insulin-dependent diabetes mellitus.
BACKGROUND
Simultaneous pancreas-kidney transplantation has become a widely accepted treatment option for selected uremic patients with insulin-dependent diabetes mellitus (IDDM). Patient survival rates at 1 year exceed 90%, and rates of pancreas graft survival, 70%. However, solitary pancreas transplantation for nonuremic patients with IDDM has been controversial because of the less favorable outcome and the need for long-term immunosuppression with its associated morbidity and mortality.


METHODS
We studied the outcome of 225 solitary pancreas transplants during three immunosuppressive eras: the precyclosporine (CsA) era (n=83), the CsA era (n=118), and the tacrolimus era (n=24). Only patients with labile IDDM (e.g., hypoglycemic unawareness, insulin reactions, > or = 2 failed attempts at intensified insulin therapy for metabolic control) underwent solitary pancreas transplantation. Using univariate and multivariate analyses, we looked at patient and graft survival, the risk of surgical complications, and native kidney function during these three eras.


RESULTS
Pancreas graft survival improved significantly over time: 34% at 1 year after transplantation in the pre-CsA era, 52% in the CsA era, and 80% in the tacrolimus era (P=0.002). Pancreas graft loss due to rejection decreased from 50% at 1 year in the pre-CsA era, to 34% in the CsA era, to 9% in the tacrolimus era (P=0.008). The rate of technical failures (i.e., the risk of surgical complications) decreased from 30% in the pre-CsA era, to 14% in the CsA era, to 0% in the tacrolimus era (P=0.001). Patient survival rates at 1 year have ranged between 88% and 95% in the three eras (P=NS). Matching for at least one antigen on each HLA locus and avoiding HLA-B mismatches significantly decreased the incidence of rejection. The incidence of native kidney failure due to drug-induced toxicity decreased significantly over time, in part because only recipients with pretransplant creatinine clearance > or = 80 ml/min received transplants.


CONCLUSIONS
Solitary pancreas transplantation has become a viable alternative for nonuremic patients with labile IDDM. The risks of surgical complications and drug-induced nephrotoxicity have significantly decreased over time. Using tacrolimus as the mainstay immunosuppressant, patient and graft survival rates now no longer trail those of simultaneous pancreas-kidney transplantation.
Gruessner
R W
RW
Department of Surgery, University of Minnesota, Minneapolis 55455, USA.
Sutherland
D E
DE
Najarian
J S
JS
Dunn
D L
DL
Gruessner
A C
AC
D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000628:therapy*; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D011241:Prednisone / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D014511:Uremia / Q000150:complications*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone; D016559:Tacrolimus