Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2015; 21(12): 3657-3662
Published online Mar 28, 2015. doi: 10.3748/wjg.v21.i12.3657
Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B
Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang
Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Author contributions: Jia HY and Ding F contributed equally to this work; all authors contributed to this manuscript.
Supported by National Key Program for Infectious Diseases of China (to Yang YD), No. 2013ZX10002001; and 12th Five-Year Significant New Drugs Creation Plan of the Ministry of Science and Technology of China (to Yang YD), No. 2011ZX09302-003-03.
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: Dr. Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. yangyida65@163.com
Telephone: +86-571-87236755 Fax: +86-571-87236755
Received: September 16, 2014
Peer-review started: September 19, 2014
First decision: October 29, 2014
Revised: November 10, 2014
Accepted: January 21, 2015
Article in press: January 21, 2015
Published online: March 28, 2015
Processing time: 194 Days and 23.4 Hours
Abstract

AIM: To evaluate urine β2-microglobulin (β2-M), retinol-binding protein (RBP) excretion, and renal impairment with adefovir dipivoxil (ADV) for chronic hepatitis B.

METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy (n = 90) or ADV plus lamivudine combination therapy (n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate (eGFR) at the initiation of antiviral therapy and every 6 mo for a period of five years.

RESULTS: Urine β2-M abnormalities were observed in patients during the first (n = 3), second (n = 7), third (n = 11), fourth (n = 16), and fifth (n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first (n = 2), second (n = 8), third (n = 12), fourth (n = 15), and fifth (n = 22) year of ADV treatment. eGFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in eGFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and eGFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment.

CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.

Keywords: Adefovir dipivoxil; Entecavir; Retinol binding protein; Renal impairment; Urine β2-microglobulin

Core tip: Identifying a reliable and sensitive biomarker of early renal dysfunction would be helpful for facilitating early intervention and evaluating the effectiveness of treatments for chronic hepatitis B. Urinary β2-microglobulin and retinol-binding protein are early markers of nephrotoxicity induced by nephrotoxic substances, cardiac surgery, diabetes mellitus, or hypertension. This study shows that long-term adefovir dipivoxil therapy in patients with chronic hepatitis B results in renal impairment that correlates with abnormalities in these markers.