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Pharmacogenetic determinants of kidney-associated urinary and serum abnormalities in antiretroviral-treated HIV-positive patients

The Pharmacogenomics Journal volume 20, pages 202–212 (2020)Cite this article

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Abstract

Tenofovir disoproxyl fumarate (TDF) has been associated with renal tubular abnormalities, phosphaturia and proteinuria (retinol binding protein, RBP, loss): vitamin D (VD) and PTH affect these markers. Aim was to understand if some single nucleotide polymorphisms (SNPs) were predictors of renal abnormalities in an Italian cohort of HIV-affected patients. DNA was analyzed through real-time PCR, urinary RBP corrected by creatinine (uRBP/Cr). The majority of patients received TDF. Abnormal uRBP/Cr was more frequent in TDF recipients: eGFR <90 mL/min and TDF were predictors in the whole cohort, whereas eGFR <90 mL/min, TDF concentrations and CYP24A1-3999TT in TDF-treated patients. Phosphate levels were higher low VD level patients: age <50 years, CYP27B1 + 2838CC genotype and non-European ancestry were predictors. PTH levels were border-line higher in TDF patients: non-European ancestry, females, TDF, VD levels < 30 ng/mL and SLC28A2-124CT/TT and ABCC2-24CC were predictors. For the first time, SNPs were associated with PTH, phosphate, calcium and tubular dysfunction in HIV-infected patients.

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Acknowledgements

We thank CoQua Lab (www.coqualab.it) for its methodological support and assistance in the preparation and execution of the study and analysis. This research was supported by research grant from Gilead (Gilead Fellowship Program 2012, c2b35f7351) and received funding specifically dedicated to the Department of Medical Sciences from Italian Ministry for Education, University and Research (Ministero dell’Istruzione, dell’Università e della Ricerca—MIUR) under the programme “Dipartimenti di Eccellenza 2018–2022”. Project no° D15D18000410001.

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  1. These authors contributed equally: Jessica Cusato, Andrea Calcagno

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  1. Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy

    Jessica Cusato, Andrea Calcagno, Letizia Marinaro, Valeria Avataneo, Antonio DʹAvolio, Giovanni Di Perri & Stefano Bonora

  2. Interdepartmental Center for Clinical and Experimental Pharmacology (CIFACS), University of Turin, Turin, Italy

    Antonio DʹAvolio

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AC has received grants from Gilead and Bristol-Myers Squibb (BMS), travel grants and speaker’s honoraria from Abbvie, BMS, Merck Sharp & Dohme (MSD), Gilead, Janssen-Cilag, and Viiv. GDP and SB have received grants, travel grants and consultancy fees from Abbvie, Boehringer-Inghelheim, BMS, MSD, Gilead, Janssen-Cilag, and Viiv. The other authors declare that they have no conflict of interest.

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Cusato, J., Calcagno, A., Marinaro, L. et al. Pharmacogenetic determinants of kidney-associated urinary and serum abnormalities in antiretroviral-treated HIV-positive patients. Pharmacogenomics J 20, 202–212 (2020). https://doi.org/10.1038/s41397-019-0109-x

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