A prospective, randomized clinical trial of cyclosporine reduction in stable patients greater than 12 months after renal transplantation.
BACKGROUND
For stable kidney-transplant recipients receiving triple drug therapy with cyclosporine (CsA), prednisone, and mycophenolate mofetil (MMF), it remains unclear what is the optimal dose of CsA beyond the first 6 to 12 months after transplantation. Complete CsA withdrawal has been associated with a significant incidence of acute rejection and, in some studies, chronic rejection as well.


METHODS
We performed an open, prospectively randomized, controlled clinical trial to determine whether CsA could be safely reduced by 50%. At 1 year or more posttransplant, 64 patients were randomized to either continue their stable-maintenance CsA dose (control group, n=32) or to lower their CsA dose by 50% over a 2 month period (CsA reduction group, n=32). All patients had stable renal-allograft function at the time of enrollment.


RESULTS
Within 6 months of randomization, no episode of acute rejection or graft loss occurred in either group. Patients in the CsA reduction group had a slight but significant increase in their glomerular filtration rate and a trend towards lower serum creatinine. There was also a significant decrease in mean systolic blood pressure, triglycerides, and serum uric acid levels in the CsA reduction group. No significant changes in any of these parameters were observed in the control group.


CONCLUSIONS
This study suggests that a strategy consisting of a 50% CsA reduction is safe and is not associated with the increased risk of acute rejection observed in CsA withdrawal studies. It also has the potential to improve short-term allograft function and appears to reduce cardiovascular risk factors such as hypertension and hyperlipidemia.
Pascual
Manuel
M
Renal and Transplantation Units, Massachusetts General Hospital, Boston, USA. Arslan@chuv.hospud.ch
Curtis
John
J
Delmonico
Francis L
FL
Farrell
Mary Lin
ML
Williams
Winfred W
WW
Kalil
Roberto
R
Jones
Patsy
P
Cosimi
A Benedict
AB
Tolkoff-Rubin
Nina
N
D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011446:Prospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid