دانلود رایگان مقاله اوستیومالاسیا ناشی از دیپیوکسیل با دوز پایین آدفوویر

ABSTRACT

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.

5. Conclusion

In conclusion, long-term (an average term of 5 years), low-dose (10 mg/d) ADV therapy was an important cause of adult-onset, hypophosphatemic osteomalacia in Chinese individuals. Clinicians should be aware of this side effect when using ADV for antiviral therapy. For early diagnosis, we suggest clinicians to pay more attention to the serum ALP and serum phosphorus level during the course of ADV treatment. Especially when other indexes of the hepatic function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ- glutamyltranspeptidase (γ-GT), are all within normal levels, only the ALP level above normal, we should be warned of ADV-induced hypophosphatemic osteomalacia. Urine routine and arterial blood gas tests are needed when necessary. According to our results, some people may have a genetic predisposition to developing ADV-associated tubulopathy and secondary hypophosphatemic osteomalacia, which may contribute to inter-individual differences in the renal tolerance to ADV. Furthermore, larger studies are needed to establish this relationship. If these preliminary data are confirmed in prospective studies, then ADV may not be suggested for patients with predisposing genotypes as the antiviral therapy or close monitoring of tubular function must be warranted when they receiving ADV treatment.