Early Everolimus Conversion for Renal Protection in Liver Transplantation: The Sooner the Better?
Tomeczkowicz M, Sulejmani N, Jantz A, Summers B, Larson T, and Salgia R. Early Everolimus Conversion for Renal Protection in Liver Transplantation: The Sooner the Better? Am J Transplant 2019; 19:1082.
Am J Transplant
Purpose: Calcineurin inhibitors (CM) are the mainstay of immunosuppressive therapy in transplantation; however, a major side effeet limiting CM use is neph-rotoxicity. Mammalian target of rapamyein inhibitors (mTORi) are less likely to eause renal dysfunction and have demonstrated benefit in preserving renal function post-liver transplant (LT); however, few studies address the appropriate timing of mTORi conversion. Methods: This is an observational retrospective cohort study comparing renal function at 3 months post conversion to everolimus (EVR) along with a CM based immunosuppressive regimen. Early initiation (EI) (conversion between 30 and 90 days post LT) was compared to delayed initiation (DI) (conversion greater than 90 days post LT) between June 2013 andMay 2018. Theprimary outcome assessed the difference in estimated glomerular filtration rate (eGFR) utilizing the Modification of Diet in Renal Disease (MDRD) equation after 3 months of EVR therapy. Secondary outcomes assessed included incidence of biopsy proven acute rejection (BPAR). mortality, graft survival (GS), discontinuation of EVR and malignancy recurrence: Results: A total of 78 patients (pts) were included with 54 pts in the EI group and 24 pts in the DI group. Median (IQR) number of days to EVR conversion was 68 (45 to 89) days in the EI group and 142. 5 (126 to 202) days in the DI group. Most pts were not converted to EVR sooner due to slow healing of post-operative wounds. The median (IQR) EGFR at the time of EVR conversion in the EI and DI groups was 76. 5 (69 to 92) and 77 (63 to 93) mL/minper 1. 73 m2. respectively, (p=0. 913). The median (IQR) change in EGFR after 3 months post EVR initiation was 0 (-11 to 9) mL/min per 1. 73 m2 in the EI group and 0 (-15. 5 to 17) mL/min per 1. 73 m2 in the DI group, (p=0. 628). There was no difference in BPAR, mortality, GS or malignancy recurrence between the groups. EVR was most commonly discontinued due to mouth sores (5 pts in EI group), fatigue (3 pts in EI group and 2 pts in DI group), and diarrhea (4 pts in EI group). Conclusions: Switching patients to an EVR based immunosuppressive regimen early did not demonstrate a renal protective benefit at 3 months post conversion. Secondary outcomes did not differ between the two groups. Early conversion to EVR does not exude a renal protective benefit early post LT and could be delayed.