Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Mar 24, 2015; 5(1): 26-33
Published online Mar 24, 2015. doi: 10.5500/wjt.v5.i1.26
Underestimation of chronic renal dysfunction after liver transplantation: ICEBERG study
Evaristo Varo, Rafael Bañares, Magda Guilera
Evaristo Varo, Liver Transplant Unit, Hospital Clínico Universitario Santiago de Compostela, 15706 Santiago de Compostela, Spain
Rafael Bañares, Hepatology Unit, Department of Gastroenterology, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain
Magda Guilera, Medical Department, Novartis Farmacéutica, 08013 Barcelona, Spain
Author contributions: Varo E, Bañares R and Guilera M participated in the research work, the study design, data analysis and manuscript review.
Supported by Novartis Farmacéutica S.A., Spain.
Ethics approval: The study was reviewed and approved by the ethics committee at Hospital Clínic of Barcelona (Spain).
Informed consent: All study participants provided informed written consent prior to study enrollment. Informed consent document was approved by the ethics committee at Hospital Clínic of Barcelona (Spain).
Conflict-of-interest: Evaristo Varo has nothing to disclose. Rafael Bañares has given lectures in Novartis symposia partially related to the submitted work. Magda Guilera is an employee of Novartis.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at evaristo.varo.perez@sergas.es.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Evaristo Varo, MD, Liver Transplant Unit, Hospital Clínico Universitario Santiago de Compostela, Travesía de Choupana s/n, 15706 Santiago de Compostela, Spain. evaristo.varo.perez@sergas.es
Telephone: +34-981-950620 Fax: +34-981-950985
Received: October 24, 2014
Peer-review started: October 27, 2014
First decision: January 8, 2015
Revised: February 10, 2015
Accepted: March 5, 2015
Article in press: March 9, 2015
Published online: March 24, 2015
Abstract

AIM: To compare prevalence of chronic renal dysfunction (CRD) according to serum creatinine (sCr) vs estimated glomerular filtration rate (eGFR) among maintenance liver transplant patients.

METHODS: The ICEBERG study was an observational, retrospective, cross-sectional, and multicenter study. Consecutive adult patients (aged 18 years or older) with liver transplantation (LT) performed at least two years previously were recruited. Multi-organ transplant recipients were excluded. Chronic renal dysfunction was defined according to sCr based criteria in routine clinical practice (≥ 2 mg/dL) and eGFR using MDRD-4 equation (< 60 mL/min per 1.73 m2). Agreement between sCr definition and eGFR assessment was evaluated using the Kappa index. Cox regression analysis was applied to identify predictive factors for developing CRD after LT.

RESULTS: A total of 402 patients were analyzed (71.6% males). Mean ± SD age at transplant was 52.4 ± 9.8 years. Alcoholic cirrhosis without hepatocellular carcinoma was the most common reason for LT (32.8%). Mean time since LT was 6.9 ± 3.9 years. Based on sCr assessment, 35.3% of patients (95%CI: 30.6-40.0) had CRD; 50.2% (95%CI: 45.3-55.1) according to eGFR. In 32.2% of cases, sCr assessment had underestimated CRD. Multivariate analysis showed the following factors associated with developing CRD: eGFR < 60 mL/min per 1.73 m2 at three months post-transplant [hazard ratio (HR) = 4.76; 95%CI: 2.78-8.33; P < 0.0001]; calcineurin inhibitor use (HR = 2.31; 95%CI: 1.05-5.07; P = 0.0371); male gender (HR = 1.98; 95%CI: 1.09-3.60; P = 0.0260); and ≥ 10 years post-transplantation (HR = 1.95; 95%CI: 1.08-3.54; P = 0.0279).

CONCLUSION: Seven years after LT, CRD affected half our patients, which was underestimated by sCr. An eGFR < 60 mL/min per 1.73 m2 three months post-LT was predictive of subsequent CRD.

Keywords: Calcineurin inhibitor, Glomerular filtration rate, Chronic renal dysfunction, Liver transplantation, Prevalence

Core tip: We aimed to compare the prevalence of chronic renal dysfunction (CRD) according to serum creatinine (sCr) vs that based on estimated glomerular filtration rate (eGFR) among maintenance liver transplant patients. According to eGFR assessment, after seven years of post-transplant follow-up, half of patients have CRD, suggesting that the occurrence of renal dysfunction is significantly under-estimated by sCr assessment in routine practice. The study outlines the importance of early CRD detection using more sensitive tools. In this sense, eGFR at 3-mo post-transplantation provides a powerful independent predictive factor for the development of CRD in liver transplant recipients.