Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2015; 21(7): 2116-2123
Published online Feb 21, 2015. doi: 10.3748/wjg.v21.i7.2116
Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B
Motohiro Shimizu, Norihiro Furusyo, Hiroaki Ikezaki, Eiichi Ogawa, Takeo Hayashi, Takeshi Ihara, Yuji Harada, Kazuhiro Toyoda, Masayuki Murata, Jun Hayashi
Motohiro Shimizu, Norihiro Furusyo, Hiroaki Ikezaki, Eiichi Ogawa, Takeo Hayashi, Takeshi Ihara, Yuji Harada, Kazuhiro Toyoda, Masayuki Murata, Department of General Internal Medicine, Kyushu University Hospital, Fukuoka 812-8582, Japan
Jun Hayashi, Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka 813-8588, Japan
Author contributions: Shimizu M and Furusyo N contributed equally to this work; Shimizu M, Furusyo N, Ikezaki H, Ogawa E, Hayashi T, Ihara T, Harada Y, Toyoda K and Murata M designed the study, collected and analyzed the data, and wrote the paper; Hayashi J supervised the study and revised the manuscript.
Supported by (In part) Grant-in-Aid for Comprehensive Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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: Norihiro Furusyo, MD, PhD, Department of General Internal Medicine, Kyushu University Hospital, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. furusyo@gim.med.kyushu-u.ac.jp
Telephone: +81-92-6425909 Fax: +81-92-6425210
Received: July 7, 2014
Peer-review started: July 7, 2014
First decision: August 6, 2014
Revised: September 1, 2014
Accepted: October 14, 2014
Article in press: October 15, 2014
Published online: February 21, 2015
Abstract

AIM: To investigate the predictors of proximal kidney tubular dysfunction (PKTD) induced by adefovir dipivoxil (ADV) treatment for chronic hepatitis B.

METHODS: Seventy-nine patients (age at the evaluation of PKTD: 56.9 ± 10.7 years) with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively recruited. PKTD was defined by the presence of at least two of the following five abnormalities: phosphate diabetes, nondiabetic glucosuria, metabolic acidosis, β2-microglobulinuria, or renal hypouricemia. The single-nucleotide polymorphisms (SNPs) in the SLC22A6 gene encoding human organic anion transporter 1 (hOAT1) and ABCC2 encoding multidrug resistance protein 2 (MRP2) were analyzed using the TaqMan Allelic Discrimination Demonstration Kit.

RESULTS: Nine (30.0%) of the 30 ADV-treated patients were diagnosed with PKTD, while no patients without ADV developed PKTD (P < 0.001). Three patients with ADV were diagnosed with symptomatic osteomalacia. Among the patients who took ADV, those with PKTD were of higher age at initiation, had significantly longer treatment duration, and had a significantly lower body mass index than those without PKTD. The incidence of PKTD dramatically increased after 96 mo from the start of ADV administration. In contrast, the SNPs were not correlated with PKTD. Logistic regression analysis extracted older age at initiation (OR = 5.0, 95%CI: 1.1-23.4; P = 0.040) and longer treatment duration (OR = 3.2, 95%CI: 1.2-8.6; P = 0.020) as significant factors associated with PKTD.

CONCLUSION: Our results suggest that the tubular function of the kidney of older patients undergoing long-term ADV treatment should be carefully evaluated.

Keywords: Adefovir dipivoxil, Proximal kidney tubular dysfunction, Fanconi syndrome, Hepatitis B virus

Core tip: This paper reports that high prevalence rates of proximal kidney tubular dysfunction (30.0%) and symptomatic osteomalacia (10.0%) were found for chronic hepatitis B virus infection patients treated with low-dose adefovir dipivoxil (ADV) and that age at the initiation of ADV and treatment duration of ADV were independently associated with the development of proximal kidney tubular dysfunction.