The investigators of the SIMCER study set out to answer this very question. The incidence of stage 4 CKD 5 years after kidney transplant ranges from 7-21%. Up to 60% of liver transplant recipients have some degree of CKD. Studies have confirmed that the development of CKD and ESRD is a major contributor to morbidity and mortality in this population. At least some of the CKD in solid organ transplant recipients is believed to originate from calcineurin inhibitor use.
The SIMCER study randomized patients to either remain on tacrolimus or start everolimus and wean off tacrolimus 1 month after liver transplant. All patients also had to by on mycophenolate and corticosteroids. They also had to receive induction with basiliximab. Primary endpoint was eGFR as calculated by MDRD at 6 months. They randomized 188 patients in 15 centers across France. Both groups were similar with MELDs of about 19. About 20% of patients had diabetes pre-transplantation. Tacrolimus troughs ranged from 7-10 in the CNI group. Six months post conversion eGFR was 14 ml higher in the everolimus group (p=0.13). There was more proteinuria in the everolimus group although still at a low level. Treatment failure occurred in 10% of everolimus group vs. 4% in the tacrolimus group. There were more rejections in the everolimus group, which occurred in patients with low trough levels. An everolimus trough of >7 seemed to prevent rejection in almost all of the everolimus group. Similarly there were more serious adverse events in the everolimus group which was driven by rejection.
The authors conclude that switching to everolimus early after liver transplantation leads to an improvement in GFR with similar efficacy but a higher incidence of serious adverse events. This study is a step in the right direction yet several questions need to be answered. It is unclear if GFR would have been better in the tacrolimus group if target troughs were lower. In addition 6 months of f/u is very short and its hard to tell how much of the improvement in GFR is just by removing the hemodynamic affect of the CNI. Still the study does attempt to answer a very important question in solid organ transplantation and may provide us with some options when it comes to preserving renal function after liver transplantation.
Post by Dr. Vinay Nair, AJKD Blog Advisory Board member.