Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B.

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.

• Authors: Motohiro Shimizu, Norihiro Furusyo, Hiroaki Ikezaki, Eiichi Ogawa, Takeo Hayashi, Takeshi Ihara, Yuji Harada, Kazuhiro Toyoda, Masayuki Murata, Jun Hayashi
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 21 Issue 7 Pg. 2116-23 (Feb 21 2015) ISSN: 2219-2840 [Electronic] United States
• PMID: 25717246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCC2 protein, human
• Antiviral Agents
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins
• Organic Anion Transport Protein 1
• Organophosphonates
• Adenine
• adefovir dipivoxil

Topics

• Adenine (adverse effects, analogs & derivatives)
• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Antiviral Agents (adverse effects)
• Chi-Square Distribution
• Female
• Genetic Predisposition to Disease
• Hepatitis B, Chronic (diagnosis, drug therapy, epidemiology)
• Humans
• Japan (epidemiology)
• Kidney Diseases (chemically induced, diagnosis, epidemiology, genetics, physiopathology)
• Kidney Tubules, Proximal (drug effects, physiopathology)
• Logistic Models
• Male
• Middle Aged
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins (genetics)
• Odds Ratio
• Organic Anion Transport Protein 1 (genetics)
• Organophosphonates (adverse effects)
• Osteomalacia (chemically induced, epidemiology)
• Polymorphism, Single Nucleotide
• Prevalence
• Retrospective Studies
• Risk Factors
• Time Factors