Mycophenolate mofetil in pancreas transplantation.
BACKGROUND
Mycophenolate mofetil (MMF) has been shown to decrease the incidence of acute rejection episodes after kidney transplantation. The use of MMF along with tacrolimus for > or =1 year after pancreas transplantation has not been studied in a large single-center analysis.


METHODS
Between July 1, 1995 and June 30, 1997, both MMF and tacrolimus were given to 120 pancreas transplant recipients. By category, 61 underwent simultaneous pancreas-kidney transplantation (SPK); 44 underwent pancreas transplantation after previous kidney transplantation (PAK); and 15 underwent pancreas transplantation alone (PTA). By donor source, 86% of the grafts were from a cadaver, and 14% were from a living-related donor. Induction therapy was with MMF, tacrolimus, prednisone, and antithymocyte globulin (n=109) or OKT3 (n=2). Until oral intake was resumed, recipients initially received intravenous azathioprine. Side effects were as follows: gastrointestinal (GI) toxicity in 53% of recipients receiving combined MMF and tacrolimus therapy; bone marrow toxicity in 24% of recipients receiving MMF alone; nephrotoxicity in 18% and neurotoxicity in 11% of recipients receiving tacrolimus alone. We did a matched-pair analysis to compare outcome in MMF versus azathioprine recipients, using the database of the International Pancreas Transplant Registry. Matching criteria included transplantation category, transplantation number, recipient and donor age, duct management, HLA typing, and transplantation year.


RESULTS
One-year patient survival rates were 98% for SPK, 98% for PAK, and 100% for PTA (P=NS). For SPK recipients, 1-year pancreas graft survival rates were 86% with MMF versus 79% with azathioprine (P=NS); kidney graft survival rates were 96% with MMF versus 86% with azathioprine (P=NS). The incidence of first rejection episodes at 1 year was significantly lower for MMF recipients (15% with MMF versus 43% with azathioprine) (P = 0.0003). For recipients of solitary pancreas transplants (PTA and PAK), we found no difference in graft survival rates between MMF and azathioprine. The conversion rate from MMF to azathioprine at 1 year was 14% for SPK recipients, 26% for PAK, and 39% for PTA (P < 0.007). The most common reason for conversion was GI toxicity, in particular for nonuremic (PTA) or posturemic (PAK) recipients. The rates of posttransplant infection and lymphoproliferative disease were low for recipients on MMF and tacrolimus.


CONCLUSIONS
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.
Gruessner
R W
RW
Department of Surgery, University of Minnesota, Minneapolis 55455, USA.
Sutherland
D E
DE
Drangstveit
M B
MB
Wrenshall
L
L
Humar
A
A
Gruessner
A C
AC
D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016035:Pancreas Transplantation / Q000276:immunology*; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus