Minimization of maintenance immunosuppression early after renal transplantation: an interim analysis.
BACKGROUND
Chronic allograft nephropathy is the main cause of long-term renal transplant failure. Chronic use of calcineurin inhibitors contributes to its pathogenesis. Here, we report on a multicenter randomized trial to study the effects of withdrawal of cyclosporine A (CsA) from a triple immunosuppressive regimen containing CsA, prednisolone (P), and mycophenolate sodium (MPS) early after transplantation.


METHODS
Patients continued on P/CsA, P/MPS, or P and everolimus (EVL). Before withdrawal, a transplant biopsy was performed ensuring no subclinical rejection was present. Drug levels were closely monitored. The primary outcome was interstitial graft fibrosis and hyalinosis. Secondary outcome was among others graft rejection.


RESULTS
According to trial regulations, an interim analysis was performed after enrollment of half of the intended number of patients (n=113). Mean follow-up was 14+/-5 months from transplantation and 8+/-5 months from conversion. After conversion, acute rejection percentages were 3% in the P/CsA group, 22% in the P/MPS group, and 0% in the P/EVL group (P<0.009).


CONCLUSIONS
We conclude that switching immunosuppressive therapy from P/CsA/MPS to therapy with P/CsA or P/EVL at 6 months after renal transplantation is effective in preventing rejection. Double therapy with P/MPS after withdrawal of P/CsA resulted in an increase in severe acute rejection episodes. These results were the immediate reason to halt the P/MPS arm. Serum creatinine values at the latest follow-up (8+/-5 months after conversion and 14+/-5 months after transplantation) in the P/EVL group were lower than in the P/CsA group.
Bemelman
Frederike J
FJ
Department of Internal Medicine, Division of Nephrology, Academic Medical Center, Renal Transplant Unit, University of Amsterdam, Amsterdam, The Netherlands. f.j.bemelman@amc.uva.nl
de Maar
Eltjo F
EF
Press
Rogier R
RR
van Kan
Henrikus J
HJ
ten Berge
Ineke J
IJ
Homan van der Heide
Jaap J
JJ
de Fijter
Hans W
HW
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D005355:Fibrosis; D006084:Graft Rejection / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D009426:Netherlands; D011239:Prednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D011239:Prednisolone; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus