Abstract
BackgroundIntroduction of calcineurin-inhibitor (CNI) has made transplantation a miracle in the past century. However, the side effects of long-term use of CNI turn out to be one of the major challenges in the current century. Among these, renal dysfunction attracts more and more attention. Herein, we undertook a meta-analysis to evaluate the efficacy and safety of calcineurin-inhibitor (CNI) minimization protocols in liver transplant recipients with CNI-related renal dysfunction.MethodsWe included randomized trials with no year and language restriction. All data were analyzed using random effect model by Review Manager 5.0. The primary endpoints were glomerular filtration rate (GFR), serum creatinine level (sCr) and creatinine clearance rate (CrCl), and the secondary endpoints were acute rejection episodes, incidence of infection and patient survival at the end of follow-up.ResultsGFR was significantly improved in CNI minimization group than in routine CNI regimen group (Z = 5.45, P<0.00001; I2 = 0%). Likely, sCr level was significantly lower in the CNI minimization group (Z = 2.84, P = 0.005; I2 = 39%). However, CrCl was not significantly higher in the CNI minimization group (Z = 1.59, P = 0.11; I2 = 0%). Both acute rejection episodes and patient survival were comparable between two groups (rejection: Z = 0.01, P = 0.99; I2 = 0%; survival: Z = 0.28, P = 0.78; I2 = 0%, respectively). However, current CNI minimization protocols may be related to a higher incidence of infections (Z = 3.06, P = 0.002; I2 = 0%).ConclusionCNI minimization can preserve or even improve renal function in liver transplant patients with renal impairment, while sharing similar short term acute rejection rate and patient survival with routine CNI regimen.
Highlights
With 1-year liver allograft survival rates exceeding 80% [1], attention is increasingly being paid on improving long-term morbidity and mortality in liver transplant recipients
To limit the renal function in a comparable range, we only included patients with glomerular filtration rate (GFR) under 60 ml/min, serum creatinine level more than 1.5 mg/dl or creatinine clearance rate (CrCl) under 70 ml/min before enrollment according to the National Kidney Foundation (NKF) recommendation for chronic kidney disease (CKD) and the staging index used in clinical practice
Since the included 32 trials used different measures of primary outcome, we analyzed the data according to 3 different outcome measures: GFR, serum creatinine level (sCr) and CrCl
Summary
With 1-year liver allograft survival rates exceeding 80% [1], attention is increasingly being paid on improving long-term morbidity and mortality in liver transplant recipients. Renal dysfunction is the most concerned long-term complication postliver transplantation, because it was estimated that 18% of recipients would develop chronic renal failure or end-stage renal disease by 5 years post-transplant and renal dysfunction would significantly increase mortality risk [2,3,4]. Multiple factors have been reported to be involved in chronic renal impairment in liver transplant recipients [2,4,5]. We undertook a meta-analysis to evaluate the efficacy and safety of calcineurin-inhibitor (CNI) minimization protocols in liver transplant recipients with CNI-related renal dysfunction
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