Journal Article

Predictors of Kidney Tubular Dysfunction in HIV-Infected Patients Treated with Tenofovir: A Pharmacogenetic Study

Sonia Rodríguez-Nóvoa, Pablo Labarga, Vincent Soriano, Deirdre Egan, Marta Albalater, Judit Morello, Lorena Cuenca, Gema González-Pardo, Saye Khoo, David Back and Andrew Owen

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 48, issue 11, pages e108-e116
Published in print June 2009 | ISSN: 1058-4838
Published online June 2009 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/598507
Predictors of Kidney Tubular Dysfunction in HIV-Infected Patients Treated with Tenofovir: A Pharmacogenetic Study

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Background. Tenofovir is one of the most widely used antiretroviral drugs. Tenofovir undergoes renal clearance by a combination of glomerular filtration and active tubular secretion. Although rare, the mechanism by which tenofovir causes renal damage is not well characterized. We have explored the association between kidney tubular dysfunction (KTD) and polymorphisms in genes encoding drug transporters.

Methods. All consecutive, human immunodeficiency virus (HIV)-infected patients receiving tenofovir-containing antiretroviral regimens who were seen at a single institution during the first trimester of 2008 were enrolled in the study. KTD was defined by the presence of at least 2 of the following abnormalities: nondiabetic glucosuria, urine phosphate wasting, hyperaminoaciduria, β2-microglobulinuria, and increased fractional excretion of uric acid. Twelve single-nucleotide polymorphisms in the ABCC2, ABCC4, SCL22A6, SLC22A11, and ABCB1 genes were analyzed using TaqMan 5′-nuclease assays.

Results. A total of 115 HIV-infected patients were examined, of whom 19 (16.5%) had KTD. The percentage of patients with KTD was higher among those with genotype CC at position −24 of ABCC2 than among those with genotypes CT and TT (24% [16 of 68 patients] vs. 6% [3 of 47 patients]; P=.020). In a multivariate analysis, older age (odds ratio [OR], 1.1; 95% confidence interval [CI], 1.0–1.2; P=.024), lower body weight (OR, 0.9; 95% CI, 0.8–0.9; P=.048), and genotype CC at ABCC2 position −24 (OR, 5; 95% CI, 1.2–21; P=.027) were independently associated with KTD.

Conclusions. Approximately 17% of HIV-infected patients treated with tenofovir had KTD. Homozygosity for the C allele at position −24 of the ABCC2 gene was strongly associated with KTD in this population. This polymorphism may help to identify patients at greater risk for developing tenofovir-associated tubulopathy, and close monitoring of renal function is warranted for these patients.

Journal Article.  3437 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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