Monitoring and Management of Proteinuria Is Often Ignored in Patients Receiving mTOR Therapy Following Orthotopic Liver Transplantation

Purpose: Use of mTOR inhibitors, such as Everolimus (EVL), in liver transplant (LT) patients continues to rise as the side effect profile becomes more evident. Calcineurin inhibitors, suchas Tacrolimus, have an increased incidence of nephrotoxicity whereas EVL remains a viable option to decrease the likelihood of renal dysfunction. In renal transplant patients, standard of care involves regular monitoring urine protein levels. however no such consensus exists amongst LT patients. We analyzed renal function by assessing proteinuria in LT patients started on EVL. Methods: All patients receiving a LT between 2011 and 2014 treated with EVL were evaluated. Background infonnation included age, gender and race. Assessment of urine protein to creatinine (UP/C) ratios was done prior to starting EVL. Follow up UP/C ratios were analyzed after starting EVL at 3 months and anytime past 6 months. Nephrotic range was defined as spot urine protein to creatinine ratio greater than 1 gram (g). Statistics were calculated using ANOVA, T-test and Chi-squared tests. Results: 75 LT patients composed primarily of males (76%) with an average age of 60.9 years were analyzed. There were 58 Caucasians (77%) and 11 African Americans (14.7%). Out of 75 total patients, 84% of patients had a UP/C ratio measured before starting EVL. After starting EVL, 30.7% had a follow up UP/C ratio measured at any given time. 11 patients had a UP/C ratio measured at 3 months and 17 patients at any time after 6 months. Before starting EVL the mean UP/C ratio was 0.17g. At the 3 month follow-up, mean UP/C ratio was 1.30g (p=0.112). At any point past 6 months from the time EVL therapy was started, mean UP/C ratio was 1.45g (p=0.504). 56.5% of patients that had their UP/C ratio checked, EVL was discontinued. The mean number of months was 17.2 at which EVL was stopped from time of initiation. Conclusions: EVL appears to lead to a significant increase in proteinuria in LT patients with the progression of time. There is a potential for worsening renal function, however regular follow up is lacking. It remains imperative that substantial proteinuria should lead to the discontinuation of EVL to prevent further renal toxicity