Observational studyBMC infectious diseases2017
Clinical and genetic factors associated with kidney tubular dysfunction in a real-life single centre cohort of HIV-positive patients.
Observational study in BMC infectious diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023Article
- Whole genome sequencing reveals population diversity and variation in HIV-1 specific host genes.Frontiers in genetics · 2023Article
- Pharmacogenomics of drug transporters for antiretroviral long-acting pre-exposure prophylaxis for HIV.Frontiers in genetics · 2022Review
- Follow-Up of Adefovir Dipivoxil Induced Osteomalacia: Clinical Characteristics and Genetic Predictors.Frontiers in pharmacology · 2021Article
- Homozygous ofFrontiers in genetics · 2021Article
- Pharmacogenetic determinants of kidney-associated urinary and serum abnormalities in antiretroviral-treated HIV-positive patients.The pharmacogenomics journal · 2020Article
- Article
- Renal Impairment in Chronic Hepatitis B: A Review.Diseases (Basel, Switzerland) · 2018Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTenofovir (TDF) is one of the most widely used antiretroviral drug. Despite the high degree of tolerability a small percentage of patients experienced alteration in tubular function during TDF use. Intracellular TDF disposition is regulated by ATP-binding cassette (ABC) drug efflux transporters and, a reduced transport activity may be implicated in accumulation of TDF into the cells. The aim of our study was to assess the major determinants of TDF associated tubular dysfunction (KTD) in a real-life setting including the usefulness of single-nucleotide polymorphisms (SNPs) mapping into ABCC2, ABCC4 and ABCC10 genes.
methodsWe retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from April 2013 to June 2016. All patients treated with TDF who underwent a genotypization for the functional variants mapping in ABCC2 rs717620 (-24 C > T), ABCC4 rs1751034 (3463 A > G) and ABCC10 rs2125739 (T > C) were evaluated. KTD was defined as the presence of urine phosphate wasting and/or proteinuria at 24 h urine analysis.
resultsOne hundred fifty-eight patients were genotyped, of which 42 (26.6%) experienced signs of KTD. No statistical significant differences were observed among patients with or without KTD regarding age, gender, ethnicity and comorbidities (hypertension and diabetes). The percentage of patients with KTD was higher among those with "GG" genotype at rs1751034 of ABCC4 compared to patients without KTD [6 (14.3%) vs 4 (3.5%), p = 0.01]. No statistical significant differences were observed regarding the distribution of ABCC2 and ABCC10 SNPs. Carriers of "G" allele in homozygous status at rs1751034 of ABCC4 showed a significant association with KTD (Odds Ratio 4.67, 95% CI 1.25-17.46, p = 0.02) in bivariate analysis, but this association was lost in multivariable analysis. A significant association between bone diseases and KTD was observed (Odds Ratio 3.178, 95%CI 1.529-6.603, p = 0.002).
conclusionsAccording to our results ABCC4 rs1751034 could be a genetic determinant of KTD; however validation studies are needed for therapy personalization. Noteworthy, a strong association between bone disease and KTD was also observed.
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