Improvement of renal function after the switch from a calcineurin inhibitor to everolimus in liver transplant recipients with chronic renal dysfunction

Abstract

Chronic renal dysfunction is a frequent and severe complication in solid-organ transplant recipients. Calcineurin inhibitors (CNIs) are the main pathogenic factors of renal dysfunction. Switching from CNIs to nonnephrotoxic drugs, such as mammalian target of rapamycin inhibitors (everolimus and sirolimus), can improve renal function in these patients, but available data about the efficacy and safety of everolimus in liver transplant recipients are scarce. Twenty-one liver transplant recipients (19 males, mean age ϭ 60.6 Ϯ 7.8 years) with chronic renal dysfunction (creatinine Ն 1.5 mg/dL) were prospectively included. The basal creatinine values were 1.79 Ϯ 0.39 mg/dL (range ϭ 1.50-2.90 mg/dL). The basal creatinine clearance, evaluated with the Cockroft-Gault formula, was 54.64 Ϯ 12.47 mL/minute. Everolimus was initiated at a dosage of 0.75 mg twice daily, with target levels of 3 to 8 ng/mL. The withdrawal of CNIs was initiated after the target levels of everolimus were reached. Periodic controls of the weight, arterial pressure, liver function tests, serum creatinine, everolimus levels, proteinuria, creatinine clearance, and glomerular filtration rate at days 30, 90, 180, and 360 were made. Chronic renal dysfunction is a frequent and severe complication in solid-organ transplant recipients. Half of liver transplant patients present a variable grade of renal dysfunction, and in 8% to 28%, advanced renal failure is established. The prevalence of renal dysfunction in this population increases as the posttransplantation follow-up period lengthens. 1-5 A large study evaluating the data for 36,849 liver transplant recipients showed a 5-year accumulated incidence of chronic renal dysfunction [defined as a glomerular filtration rate (GFR) less than 29 mL/minute/m 2 ] of 18%. 6 The development of posttransplantation renal failure has a significant negative impact on the survival of liver transplant recipients.

Conversion to everolimus in maintenance liver transplant patients: A multicenter, retrospective analysis

“…Previous reports have described no rejection episodes after the introduction of everolimus, [19][20][21] but in 2 trials in which CNI therapy and adjuvant immunosuppressants were withdrawn relatively aggressively, the rates of rejection were 7% 18 and 10%. 17 In the current study, in which there were no protocol-specified withdrawals of other agents, there was a very low rate of acute rejection (<2.0%).…”

“…Single-arm studies have demonstrated that maintenance liver transplant patients can be converted from CNIs to everolimus safely at later time points with a low rate of acute rejection. [17][18][19][20][21][22] Like kidney transplant recipients, 23 liver transplant recipients with kidney dysfunction apparently need to be switched from CNI immunosuppression to everolimus either early after transplantation 16 or before the establishment of severe dysfunction. 17 In clinical practice, some centers now initiate everolimus in maintenance liver transplant patients who develop kidney dysfunction or, less frequently, posttransplant neoplasms and attempt to withdraw CNI therapy.…”

Use of Everolimus in Liver Transplantation

“…In a retrospective observational study, Saliba et al [26] found the improvement in renal function to be greater when conversion to EVR was within first year post-LT (eGFR increased from 77.5 to 90.0 mL/min, P = 0.04) vs those who were converted beyond 1 year post-LT (eGFR increased from 59.1 to 64.6 mL/min, P = 0.01) [26] . The findings Castroagudín et al [25] reported in a retrospective study echoed the less remarkable renal improvement (eGFR improved by 7.7 mL/min at month 12) when conversion to EVR occurred at 5.2 ± 3.1 years from transplant. Thus, the best time point for conversion to EVR for optimal renoprotective effect is still unclear and further studies are warranted.…”

Everolimus in clinical practice after liver transplantation: a single-center experience

“…По данным некоторых исследований, использова-ние иммуносупрессивного протокола с эверолиму-сом и отменой ИКН обеспечивало лучшую функ-цию почек без повышения риска отторжения [15]. Однако в проспективном рандомизированном мно-гоцентровом исследовании в течение 6 мес.…”