Everolimus as a Calcineurin Inhibitor-Sparing Immunosuppressive Agent in Lung Transplant Recipients With Renal Impairment

Abstract

SESSION TITLE: Transplant SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Calcineurin inhibitors (CNI) are considered a key component of maintenance immunosuppression following lung transplantation. However, CNI nephrotoxicity is a common and serious problem amongst lung transplant recipients. Everolimus (ERL), an inhibitor of the mechanistic target of rapamycin (mTOR), has been used as a CNI sparing immunosuppressive agent to allow renal recovery in patients with progressive renal impairment. Nevertheless, there is limited evidence to support the efficacy of this strategy to prevent rejection. This study aimed to evaluate the effect of ERL on renal and lung function in lung transplant recipients. METHODS: We conducted a retrospective analysis within a state-wide lung transplant service in Australia. Medical and pharmacy records were used to identify lung transplant recipients who were commenced on ERL from 2004 to 2015. Patients who received at least 6 consecutive months of ERL therapy during this period were included in the analysis. We recorded renal function and lung function 6 months before and 6 months after the initiation of ERL. Creatinine clearance (CrCl), derived from the Cockroft-Gault equation, was used as a measure of renal function. Lung function was reported as the percent predicted FEV1 and FVC. RESULTS: 44 patients were included in the analysis. The mean age was 49 ± 15 years. ERL was initiated at a median of 476 days (interquartile range 219-1247) post-transplant. The indication for ERL was renal impairment in 94%, malignancy in 4% and CNI related neurotoxicity in 2% of patients. After initiating ERL, 46% of patients had CNI ceased and the rest had a substantial dose reduction. At ERL initiation, mean CrCl was 52.6 ± 3.3 ml/min, mean percent predicted FEV1 70 ± 3% and FVC 77 ± 3%. In the 6 months prior to commencing ERL, there was a mean change in CrCl of -8.9 ± 2.4 ml/min (P=0.003), FEV1 -3.4 ± 1.9% (p=0.696), and FVC -1.2 ± 1.5% (p=1.000). 6 months after initiating ERL, the mean change in CrCl was +11.2 ± 2.4 ml/min (p<0.0001), FEV1 -5.3 ± 1.7% (p=0.024), and FVC -3.9 ± 1.4% (p=0.049). Excluded from the analysis were 8 patients who were on ERL for less than 6 months. 6 patients had ERL ceased; 2 for rejection, 2 for suspected pneumonitis, 1 for drug intolerance and 1 to aid wound healing after a motor vehicle accident. There were 2 deaths during this period; one due to chest sepsis and the other from liver failure, neither of which could be directly related to toxicity from ERL. These 8 patients received ERL for at least 3 months and were included in a 3-months analysis. At 3 months, there was a similar increase in CrCl of +11.6 ± 2.3 ml/min (p<0.0001) and no significant change in FEV1 and FVC. CONCLUSIONS: In lung transplant recipients with renal impairment, the use of ERL as a CNI sparing agent is associated with improvement in renal function. However, the efficacy of this maintenance immunosuppression strategy in preventing rejection requires elucidation with further studies. CLINICAL IMPLICATIONS: The use of ERL allows CNI withdrawal and renal recovery in lung transplant recipients with renal impairment. These patients should be closely followed up with frequent monitoring of lung function. DISCLOSURE: The following authors have nothing to disclose: Shaun Yo, Tim Coughlan, Steve Ivulich, Eldho Paul, Gregory Snell, Solomon Menahem No Product/Research Disclosure Information