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

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

doi:10.1038/s41397-019-0109-x

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

Pharmacogenomics J. 2020 Apr;20(2):202-212. doi: 10.1038/s41397-019-0109-x. Epub 2019 Oct 16.

Authors

Jessica Cusato¹, Andrea Calcagno², Letizia Marinaro², Valeria Avataneo², Antonio DʹAvolio^{2

3}, Giovanni Di Perri², Stefano Bonora²

Affiliations

¹ Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy. [email protected].
² Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
³ Interdepartmental Center for Clinical and Experimental Pharmacology (CIFACS), University of Turin, Turin, Italy.

PMID: 31619748
DOI: 10.1038/s41397-019-0109-x

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / genetics
Adult
Anti-HIV Agents / adverse effects*
Anti-HIV Agents / blood
Anti-HIV Agents / therapeutic use
Cohort Studies
Creatinine / urine
Female
Glomerular Filtration Rate
HIV Infections / drug therapy*
HIV Infections / genetics
Humans
Kidney Diseases / chemically induced
Kidney Diseases / genetics*
Logistic Models
Male
Middle Aged
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins / genetics
Phosphates / blood
Polymorphism, Single Nucleotide*
Receptors, Calcitriol / genetics
Retinol-Binding Proteins / urine
Tenofovir / adverse effects*
Tenofovir / blood
Tenofovir / therapeutic use
Vitamin D3 24-Hydroxylase / genetics

Substances

ABCB1 protein, human
ABCC10 protein, human
ABCC2 protein, human
ATP Binding Cassette Transporter, Subfamily B
Anti-HIV Agents
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins
Phosphates
Receptors, Calcitriol
Retinol-Binding Proteins
VDR protein, human
Tenofovir
Creatinine
CYP24A1 protein, human
Vitamin D3 24-Hydroxylase