Léna G Dietrich1, Catalina Barceló2, Christian W Thorball3,4, Lene Ryom5, Felix Burkhalter6, Barbara Hasse7, Hansjakob Furrer8, Maja Weisser9, Ana Steffen10, Enos Bernasconi11, Matthias Cavassini12, Sophie de Seigneux13, Chantal Csajka2, Jacques Fellay3,4, Bruno Ledergerber7, Philip E Tarr1. 1. University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz. 2. Division of Clinical Pharmacology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne. 3. Swiss Institute of Bioinformatics, Lausanne. 4. School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland. 5. Center of Excellence for Health, Immunity and Infections, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark. 6. University Department of Medicine and Nephrology Service, Kantonsspital Baselland, University of Basel, Bruderholz. 7. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Lugano. 8. Department of Infectious Diseases, Bern University Hospital, University of Bern, Lugano. 9. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Lugano. 10. Division of Infectious Diseases, Kantonsspital St Gallen, Lugano. 11. Division of Infectious Diseases, Ospedale Regionale, Lugano. 12. Division of Infectious Diseases, Lausanne University Hospital. 13. Division of Nephrology, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Switzerland.
Abstract
BACKGROUND: In human immunodeficiency virus (HIV), the relative contribution of genetic background, clinical risk factors, and antiretrovirals to chronic kidney disease (CKD) is unknown. METHODS: We applied a case-control design and performed genome-wide genotyping in white Swiss HIV Cohort participants with normal baseline estimated glomerular filtration rate (eGFR >90 mL/minute/1.73 m2). Univariable and multivariable CKD odds ratios (ORs) were calculated based on the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) score, which summarizes clinical CKD risk factors, and a polygenic risk score that summarizes genetic information from 86 613 single-nucleotide polymorphisms. RESULTS: We included 743 cases with confirmed eGFR drop to <60 mL/minute/1.73 m2 (n = 144) or ≥25% eGFR drop to <90 mL/minute/1.73 m2 (n = 599), and 322 controls (eGFR drop <15%). Polygenic risk score and D:A:D score contributed to CKD. In multivariable analysis, CKD ORs were 2.13 (95% confidence interval [CI], 1.55-2.97) in participants in the fourth (most unfavorable) vs first (most favorable) genetic score quartile; 1.94 (95% CI, 1.37-2.65) in the fourth vs first D:A:D score quartile; and 2.98 (95% CI, 2.02-4.66), 1.70 (95% CI, 1.29-2.29), and 1.83 (95% CI, 1.45-2.40), per 5 years of exposure to atazanavir/ritonavir, lopinavir/ritonavir, and tenofovir disoproxil fumarate, respectively. Participants in the first genetic score quartile had no increased CKD risk, even if they were in the fourth D:A:D score quartile. CONCLUSIONS: Genetic score increased CKD risk similar to clinical D:A:D score and potentially nephrotoxic antiretrovirals. Irrespective of D:A:D score, individuals with the most favorable genetic background may be protected against CKD.
BACKGROUND: In human immunodeficiency virus (HIV), the relative contribution of genetic background, clinical risk factors, and antiretrovirals to chronic kidney disease (CKD) is unknown. METHODS: We applied a case-control design and performed genome-wide genotyping in white Swiss HIV Cohort participants with normal baseline estimated glomerular filtration rate (eGFR >90 mL/minute/1.73 m2). Univariable and multivariable CKD odds ratios (ORs) were calculated based on the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) score, which summarizes clinical CKD risk factors, and a polygenic risk score that summarizes genetic information from 86 613 single-nucleotide polymorphisms. RESULTS: We included 743 cases with confirmed eGFR drop to <60 mL/minute/1.73 m2 (n = 144) or ≥25% eGFR drop to <90 mL/minute/1.73 m2 (n = 599), and 322 controls (eGFR drop <15%). Polygenic risk score and D:A:D score contributed to CKD. In multivariable analysis, CKD ORs were 2.13 (95% confidence interval [CI], 1.55-2.97) in participants in the fourth (most unfavorable) vs first (most favorable) genetic score quartile; 1.94 (95% CI, 1.37-2.65) in the fourth vs first D:A:D score quartile; and 2.98 (95% CI, 2.02-4.66), 1.70 (95% CI, 1.29-2.29), and 1.83 (95% CI, 1.45-2.40), per 5 years of exposure to atazanavir/ritonavir, lopinavir/ritonavir, and tenofovir disoproxil fumarate, respectively. Participants in the first genetic score quartile had no increased CKD risk, even if they were in the fourth D:A:D score quartile. CONCLUSIONS: Genetic score increased CKD risk similar to clinical D:A:D score and potentially nephrotoxic antiretrovirals. Irrespective of D:A:D score, individuals with the most favorable genetic background may be protected against CKD.
Authors: Jan A Roth; Gorjan Radevski; Catia Marzolini; Andri Rauch; Huldrych F Günthard; Roger D Kouyos; Christoph A Fux; Alexandra U Scherrer; Alexandra Calmy; Matthias Cavassini; Christian R Kahlert; Enos Bernasconi; Jasmina Bogojeska; Manuel Battegay Journal: J Infect Dis Date: 2021-10-13 Impact factor: 7.759