The effect of maintenance immunosuppression medication on the change in kidney allograft function.
BACKGROUND
The optimum maintenance immunosuppression regimen for kidney transplant recipients is uncertain. In this study we determined the effect of maintenance immunosuppression medications on the rate of kidney allograft function loss defined by the annualized change in glomerular filtration rate (GFR).


METHODS
We studied 40,963 first kidney only transplant recipients between 1987 and 1996 with allograft survival of at least two years in the United States Renal Data System. Linear regression methods were applied to serial GFR estimates after transplantation to determine the annualized change in GFR. Patients were classified according to the type of maintenance calcineurin and purine metabolism inhibitor received after transplantation. Multiple linear regression was used to determine the independent effect of maintenance immunosuppression medications on the annualized change in GFR (mL/min/1.73m2/year).


RESULTS
Compared to patients who received cyclosporine microemulsion (Neoral), a slower decline in GFR was observed in tacrolimus-treated patients (1.60 mL/min/1.73m2/year, 95% CI 1.22-1.97, P < 0.001) and patients who did not receive calcineurin inhibitors (0.82 mL/min/1.73m2/year, 95% CI 0.08-1.56, P= 0.03). In contrast, compared to compared to patients who received Neoral, a faster decline in GFR was observed in patients who received the original oil-based formulation of cyclosporine (Sandimmune) (-0.16 mL/min/1.73m2/year, 95% CI -0.003 to -0.32, P= 0.04) and patients with unknown calcinuerin inhibitor exposure (-2.11 mL/min/1.73m2/year, 95% CI -2.27 to -1.95, P < 0.001). Compared to patients who received azathioprine, patients who received mycophenolate mofetil (MMF) had a slower decline in GFR (0.61 mL/min/1.73m2/year, 95% CI 0.14-1.08, P= 0.01) and patients with unknown purine metabolism inhibitor exposure had a faster decline in GFR (-0.61 mL/min/1.73m2/year, 95% CI -0.75 to -0.47, P < 0.001.) In a subgroup analysis of patients who received a transplant after 1993, the decline in GFR was slower for tacrolimus compared to neoral treated patients (1.64 mL/min/1.73m2/year, 95% CI 1.15-2.14, P < 0.001) but was not different for MMF compared to azathioprine-treated patients (0.24 mL/min/1.73m2/year, 95% CI -0.38-0.85, P= 0.45).


CONCLUSIONS
Tacrolimus and MMF were the calcineurin inhibitor and purine metabolism inhibitor associated with the most favorable effects on rates of change in allograft function. Because most transplant recipients establish a low baseline level of allograft function, the effect of immunosuppression medication on GFR decline should be considered when selecting a maintenance immunosuppression regimen.
Gill
John S
JS
Division of Nephrology, St. Paul's Hospital, Vancouver, British Columbia, Canada. jgill@providencehealth.bc.ca
Tonelli
Marcello
M
Mix
Christian H
CH
Johnson
Nathan
N
Pereira
Brian J G
BJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000008:administration & dosage; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage*; D016208:Databases, Factual; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016559:Tacrolimus / Q000008:administration & dosage; D014184:Transplantation, Homologous
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus