{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T02:04:36Z","timestamp":1755223476826,"version":"3.43.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n            <jats:title>Objectives<\/jats:title>\n            <jats:p>The purpose of this case-control study was to verify the association between single nucleotide polymorphisms (SNPs) in genes encoding drug transporters related to tenofovir disoproxil fumarate (TDF) and proximal renal tubular dysfunction (PRTD), and the association between PRTD and clinical characteristics.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The \u2018cases\u2019 met the diagnostic criteria for PRTD, determined by the presence of two or more of the following abnormalities: non-diabetic glycosuria, metabolic acidosis, increased uric acid and phosphorus excretion, decreased tubular phosphorus reabsorption and \u03b22-microglobulinuria. We analyzed eight SNPs in ABCC2, ABCC4, ABCC10 and SLC28A2 genes. Genotyping was performed using real-time PCR.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of the 204 people living with HIV, 38 (18.6%) met the criteria for diagnosis of PRTD and 131 were male (64.2%), with a mean age of 49\u2009years and a history of previous antiretroviral therapy for an average of 5\u2009years. In the multivariate analysis, older individuals, TDF use, protease inhibitor, antihypertensives and anticonvulsants were associated with a risk of developing PRTD. Increased excretion of \u03b22microglobulin was associated with the A\/G genotype of rsCC8187710 from ABCC2 (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.003) and the following genotypes of ABCC4 SNPs: A\/G from rs1059751 (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.023), G\/G from rs1059751 (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.030) and C\/C of rs3742106 (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.041). The increase in the fraction of excreted phosphorus was associated with the C\/T genotype of SNCC rsP40037 from ABCC2 (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.0041).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The results indicate an important relationship between SNPs associated with these markers and changes in proximal renal tubule function, and thus support their use as biomarkers for the early detection of PRTD risk.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000482","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T14:05:44Z","timestamp":1666101944000},"page":"293-300","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Proximal tubular dysfunction related to tenofovir in people living with HIV\/AIDS: a pharmacogenetic study"],"prefix":"10.1097","volume":"32","author":[{"given":"Rita De Cassia Albuquerque","family":"Soares","sequence":"first","affiliation":[{"name":"Infectology Sector, Hospital Das Cl\u00ednicas, Federal University of Pernambuco"},{"name":"Postgraduate At Tropical Medicine, Hospital Das Cl\u00ednicas, Federal University of Pernambuco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo S\u00e9rgio Ramos","family":"De Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Infectology Sector, Hospital Das Cl\u00ednicas, Federal University of Pernambuco"},{"name":"Aggeu Magalh\u00e3es Institute \u2013 Oswaldo Cruz Foundation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas Andr\u00e9 Cavalcanti","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Pathology Department, Federal University Of Pernambuco"},{"name":"Immunopathology Laboratory, Federal University of Pernambuco, Recife - PE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ant\u00f4nio Victor Campos","family":"Coelho","sequence":"additional","affiliation":[{"name":"Molecular Biology Departament, Federal University of Para\u00edba, Jo\u00e3o Pessoa - PB"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kledoaldo","family":"Lima","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Hospital Das Cl\u00ednicas, Federal University of Pernambuco, Recife - PE, Brazil"},{"name":"European Virus Bioinformatics Center, Leutragraben, Jena, Germany."},{"name":"Faculdade Pernambucana de Sa\u00fade, Recife - PE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heloisa Ramos Lacerda","family":"De Melo","sequence":"additional","affiliation":[{"name":"Postgraduate At Tropical Medicine, Hospital Das Cl\u00ednicas, Federal University of Pernambuco"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"R1-20250811","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1097\/MNH.0000000000000392","article-title":"Potential kidney toxicity from the antiviral drug tenofovir: new indications. new formulations. and a new prodrug.","volume":"27","author":"Chan","year":"2018","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"R2-20250811","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/tpj.2015.71","article-title":"Clinical pharmacology of tenofovir clearance: a pharmacokinetic\/pharmacogenetic study on plasma and urines.","volume":"16","author":"Calcagno","year":"2015","journal-title":"Pharmacogenomics J"},{"key":"R7-20250811","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1310\/hct1304-189","article-title":"Renal toxicity associated associated with antiretroviral therapy HIV 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variants of ABCC10, a novel tenofovir transporter, are associated wtih kidney tubular dysfunction.","volume":"204","author":"Pushpakom","year":"2011","journal-title":"J Infect Dis"},{"key":"R12-20250811","doi-asserted-by":"crossref","first-page":"e0147724","DOI":"10.1371\/journal.pone.0147724","article-title":"A single-nucleotide polymorphism in ABCC4 is associated with tenofovir-related beta2-microglobulinuria in Thai patients with HIV-1 infection.","volume":"11","author":"Likanonsakul","year":"2016","journal-title":"PLoS One"},{"key":"R13-20250811","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1177\/0956462418786562","article-title":"Polymorphisms of tenofovir disoproxil fumarate transporters and risk of kidney tubular dysfunction in HIV-positive patients: genetics of tenofovir transporters.","volume":"29","author":"Danjuma","year":"2018","journal-title":"Int J STD AIDS"},{"key":"R14-20250811","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3389\/fphar.2014.00248","article-title":"The role of drug transporters in the kidney: lessons from tenofovir.","volume":"5","author":"Moss","year":"2014","journal-title":"Front Pharmacol"},{"key":"R15-20250811","doi-asserted-by":"crossref","first-page":"e0141931","DOI":"10.1371\/journal.pone.0141931","article-title":"Drug transporter genetic variants are not associated with TDF-related renal dysfunction in patients with HIV-1 infection: a pharmacogenetic study.","volume":"10","author":"Nishijima","year":"2015","journal-title":"PLoS One"},{"key":"R16-20250811","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1086\/508546","article-title":"Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy.","volume":"194","author":"Izzedine","year":"2006","journal-title":"J Infect Dis"},{"key":"R18-20250811","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.diagmicrobio.2018.07.001","article-title":"Tenofovir alafenamide and tenofovir disoproxil fumarate are not transported by concentrative nucleoside transporter 2.","volume":"94","author":"Cusato","year":"2019","journal-title":"Diagn Microbiol Infect Dis"},{"key":"R20-20250811","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/bcpt.13196","article-title":"Pharmacogenomics research and clinical implementation in Brazil.","volume":"124","author":"Rodrigues-Soares","year":"2019","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"R21-20250811","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1111\/j.1365-2036.2012.05093.x","article-title":"Renal tubular dysfunction during long\u201a \u00c4\u00eaterm adefovir or tenofovir therapy in chronic hepatitis B.","volume":"35","author":"Gara","year":"2012","journal-title":"Aliment Pharmacol Ther"},{"key":"R22-20250811","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/ki.2011.124","article-title":"Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy.","volume":"80","author":"Dauchy","year":"2011","journal-title":"Kidney Int"},{"key":"R25-20250811","first-page":"97","article-title":"Intracellular pharmacokinetics of antiretroviral agentes.","volume":"9","author":"Owen","year":"2004","journal-title":"J HIV Ther"},{"key":"R27-20250811","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.jiac.2018.03.002","article-title":"Tenofovir disoproxil fumarate co-administered with lopinavir\/ritonavir is strongly associated with tubular damage and chronic kidney disease.","volume":"24","author":"Mizushima","year":"2018","journal-title":"J Infect Chemother"},{"key":"R28-20250811","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.tips.2009.10.001","article-title":"The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters.","volume":"31","author":"Kis","year":"2010","journal-title":"Trends Pharmacol Sci"},{"key":"R29-20250811","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s40262-017-0506-8","article-title":"Renal drug transporters and drug interactions.","volume":"56","author":"Ivanyuk","year":"2017","journal-title":"Clin Pharmacokinet"},{"key":"R31-20250811","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/cid\/ciu617","article-title":"Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV medicine association of the infectious diseases society of America.","volume":"59","author":"Lucas","year":"2014","journal-title":"Clin Infect Dis"}],"container-title":["Pharmacogenetics and 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