title: Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our results suggest that the tubular function of the kidney of older patients undergoing long-term ADV treatment should be carefully evaluated.
authors.affiliation: 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.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: 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.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.affiliation: 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.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikezaki
authors.affiliation: 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.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ogawa
authors.affiliation: 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.
authors.forename: Takeo
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: 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.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ihara
authors.affiliation: 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.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Harada
authors.affiliation: 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.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Toyoda
authors.affiliation: 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.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Murata
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects*; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D016017:Odds Ratio; D027362:Organic Anion Transport Protein 1 / Q000235:genetics; D063065:Organophosphonates / Q000009:adverse effects*; D010018:Osteomalacia / Q000139:chemically induced / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000225:Adenine; D000998:Antiviral Agents; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027362:Organic Anion Transport Protein 1; D063065:Organophosphonates; C000715087:ABCC2 protein, human; C106812:adefovir dipivoxil
keywords: Adefovir dipivoxil; Fanconi syndrome; Hepatitis B virus; Proximal kidney tubular dysfunction