Osteomalacia induced by long-term low-dose adefovir dipivoxil: Clinical characteristics and genetic predictors.
CONTEXT
Adefovir dipivoxil (ADV) was an important cause of adult-onset hypophosphatemic osteomalacia. However, its clinical characteristics and mechanisms have not been well defined.


OBJECTIVE
The objective of the study was to summarize the clinical characteristics of ADV-induced osteomalacia and to explore the association between ADV-associated tubulopathy and polymorphisms in genes encoding drug transporters.


DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURE
Seventy-six affected patients were clinically studied. The SLC22A6 and ABCC2 genes were screened and compared with healthy people from the HapMap.


RESULTS
Hypophosphatemia, high serum alkaline phosphatase (ALP) levels, hypouricemia, nondiabetic glycosuria, proteinuria, metabolic acidosis and high bone turnover markers were the main metabolic characteristics. Fractures and pseudofractures occurred in 39 patients. Stopping ADV administration, supplementing calcitriol and calcium was effective during the follow-up period. Single SNP analysis revealed a higher percentage of the G/A genotype at c.2934 in exon 22 of the ABCC2 gene (rs3740070) in patients than in healthy people (12% [7 of 58 patients] vs. 0% [0 of 45 patients]; P=0.017), while there was no subject with homozygosity for the A allele at c.2934.


CONCLUSIONS
ADV can be nephrotoxic at a conventional dosage. The G/A genotype at c.2934 of the ABCC2 gene may be a predictor of patients at greater risk for developing ADV-associated tubulopathy. Larger case-control studies are needed to further verify this finding.
['Wei|Zhe|Z|', 'He|Jin-Wei|JW|', 'Fu|Wen-Zhen|WZ|', 'Zhang|Zhen-Lin|ZL|']
D000225:Adenine D000595:Amino Acid Sequence D016022:Case-Control Studies D004252:DNA Mutational Analysis D004305:Dose-Response Relationship, Drug D005260:Female D005500:Follow-Up Studies D005787:Gene Frequency D056726:Genetic Association Studies D020022:Genetic Predisposition to Disease D006801:Humans D008297:Male D008875:Middle Aged D000089762:Multidrug Resistance-Associated Protein 2 D027425:Multidrug Resistance-Associated Proteins D027362:Organic Anion Transport Protein 1 D063065:Organophosphonates D010018:Osteomalacia D020641:Polymorphism, Single Nucleotide D012307:Risk Factors D017386:Sequence Homology, Amino Acid
Adefovir dipivoxil Clinical characteristic Hypophosphatemic osteomalacia SLC22A6 ABCC2 Risk genotype