A randomized trial comparing cyclosporine with antilymphoblast-globulin-azathioprine for renal allograft recipients. Results at 2 1/2-6 years.
Between September 1980 and June 1984, 246 splenectomized, transfused renal allograft recipients were stratified according to presence of diabetes and donor source, and randomized to treatment with either cyclosporine (CsA)-prednisone (pred) or antilymphoblast-globulin (ALG--azathioprine (AZA)--prednisone. As of August 1986, mean follow-up is 47 months. Over all, actuarial patient survival is 84% and 83%, respectively at 4 years. Corresponding graft survival is 70% and 63% for CsA-treated and ALG-AZA-treated patients (NS). Within the subgroup of diabetic recipients of cadaver grafts, graft survival is 70% for CsA-treated and 53% for ALG-AZA-treated recipients (P = .035). In the CsA group, 71% required either a significant reduction in CsA dosage with the addition of azathioprine or a complete switch to azathioprine, mainly because of CsA-associated nephrotoxicity. Of those CsA patients switched at a mean time of 21.3 +/- 16.4 months posttransplant with mean serum creatinine of 2.40 +/- .67, current serum creatinine is 1.79 +/- .63. Current mean serum creatinine values are significantly greater for patients randomized to CsA-pred (1.73 +/- .60) vs. ALG-AZA-pred (1.49 +/- .59), P = .014, even though most CsA-treated patients were eventually switched. The causes of graft loss are not different between CsA and ALG-AZA randomized patients. In nondiabetics, rejection is the most common cause of graft loss (17/33), whereas in diabetics loss due to complications from overimmunosuppression or death from cardiovascular events is significantly more common (27/44) than corresponding losses in nondiabetics (6/33, P less than .05). Switching does not seem to influence the incidence or cause of graft loss. Since most patients started on CsA-prednisone are ultimately switched to triple drug therapy, the latter is now the preferred initial treatment modality.
Johnson
C P
CP
Department of Surgery, University of Minnesota, Minneapolis.
Simmons
R L
RL
Sutherland
D E
DE
Canafax
D M
DM
Ascher
N L
NL
Payne
W D
WD
Flick
B
B
Najarian
J S
JS
Fryd
D S
DS
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000628:therapy; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011897:Random Allocation
D000961:Antilymphocyte Serum; D003524:Cyclosporins; D003404:Creatinine; D001379:Azathioprine