Long-term outcome after early cyclosporine withdrawal in kidney transplantation: ten years after.
Despite long-term side effects, calcineurin inhibitors (CNI) remain a cornerstone of immunosuppression in renal transplantation. Few trials assessed the long-term outcome after early CNI withdrawal.



This intention-to-treat study assessed the 10-year outcome of 108 patients randomly converted from a cyclosporine (CsA)-mycophenolate mofetil (MMF)-prednisone regimen to a dual therapy (CsA-prednisone or MMF-prednisone) at 3 months postgraft.



At 10 years, 3.7% in the CsA group and 35.2% in the MMF group remained on the protocol regimen (P<.001). eGFR was higher in the MMF group (64.4±21 vs 49.7±14.7 mL/min/1.73 m², P<.001), although acute rejection (12 vs 4 in the CsA group, P=.03) and Class II DSA incidences were increased. CNI-related toxicity (P=.019) and moderate-to-severe IF/TA (P=.004) were higher in the CsA group. Ten-year graft and patient survivals were not different. In multivariate analysis, acute rejection remained the strongest predictor of graft loss (HR=11.64, 95% CI [5.05-26.79], P<.0001).



MMF withdrawal largely failed due to CNI toxicity, while CsA withdrawal led to increased graft failure due to uncontrolled acute rejection without increasing graft survival. From this study, it remains unclear which patients could benefit from limiting CNI exposure.
CHU Lille - Service de Néphrologie - F-59000 Lille, France. nathalie.tabibzadeh@aphp.fr.|Université de Lille - UMR 995, F-59000 Lille, France. nathalie.tabibzadeh@aphp.fr.
Nahid
N
Tabibzadeh
CHU Lille - Service de Néphrologie - F-59000 Lille, France.|Université de Lille - UMR 995, F-59000 Lille, France.
François
F
Glowacki
CHU Lille - Service de Néphrologie - F-59000 Lille, France.|Université de Lille - UMR 995, F-59000 Lille, France.
Marie
M
Frimat
Université de Lille - UMR 995, F-59000 Lille, France.|CHU Lille - Laboratoire d'Immunologie - F-59000 Lille, France.
Vincent
V
Elsermans
CHU Lille - Service de Néphrologie - F-59000 Lille, France.
François
F
Provôt
CHU Lille - Service de Néphrologie - F-59000 Lille, France.
Arnaud
A
Lionet
Université de Lille - UMR 995, F-59000 Lille, France.|CHU Lille - Laboratoire d'Anatomopathologie - F-59000 Lille, France.
Viviane
V
Gnemmi
Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, APHP, Paris, France.|UPMC Sorbonne Université Paris 06, UMR S 1155, F-75020, Paris, France.
Alexandre
A
Hertig
CHU Lille - Service de Néphrologie - F-59000 Lille, France.|Université de Lille - UMR 995, F-59000 Lille, France.
Christian
C
Noël
CHU Lille - Service de Néphrologie - F-59000 Lille, France.|Université de Lille - UMR 995, F-59000 Lille, France.
Marc
M
Hazzan
D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D009173:Mycophenolic Acid / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone

eGFR
; cyclosporine; immunosuppression; kidney transplantation; long-term follow-up