Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (the 3C Study) - results of a randomized controlled clinical trial.
Haynes R., Blackwell L., Staplin N., Herrington WG., Emberson J., Judge PK., Storey BC., Landray MJ., Harden PN., Baigent C., Friend P.
Calcineurin inhibitors (CNI e.g. tacrolimus) reduce short-term kidney transplant failure, but chronic nephrotoxicity may contribute to late transplant loss. Elective conversion to inhibitors of the mammalian target of rapamycin pathway (mTOR e.g. sirolimus) might avoid long-term CNI renal damage and improve outcomes. The 3C Study was a pragmatic randomized controlled trial comprising sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6-months post-transplant. The primary outcome of this analysis was estimated glomerular filtration rate (eGFR) at 18 months after maintenance therapy randomization. 197 patients were assigned sirolimus-based and 197 to tacrolimus-based therapy. Allocation to sirolimus had no significant effect on eGFR at 18 months: baseline-adjusted mean (SE) eGFR 53.7 (0.9) mL/min/1.73m2 in the sirolimus group versus 54.6 (0.9) mL/min/1.73m2 in the tacrolimus group (p=0.50). Biopsy-proven acute rejection (29 [14.7%]) vs 6 [3.0%]; p<0.001) and serious infections (defined as opportunistic infections or those requiring hospitalisation; 95 [48.2%] versus 70 [35.5%]; p=0.008) were more common among participants allocated sirolimus. Compared with tacrolimus-based therapy, sirolimus-based maintenance therapy did not improve transplant function at 18 months after conversion and was associated with significant hazards of rejection and infection. This article is protected by copyright. All rights reserved.