Contribution of genetic background and clinical D:A:D risk score to chronic kidney disease in Swiss HIV-positive persons with normal baseline estimated glomerular filtration rate

Abstract

BACKGROUND
In 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/min/1.73 m2). Uni- and multivariable CKD odds ratios (OR) were calculated based on the D:A:D score that summarizes clinical CKD risk factors and a polygenic risk score that summarizes genetic information from 86613 single nucleotide polymorphisms..
RESULTS
We included 743 cases (79% male; median age, 42 years; baseline eGFR 106 mL/min/1.73 m2) with confirmed eGFR drop to <60 mL/min/1.73 m2 (n=144) or ≥25% eGFR drop to <90 mL/min/1.73 m2 (n=599), and 322 controls (eGFR drop <15%; 81% male; median age, 39 years, baseline eGFR 107 mL/min/1.73 m2). Polygenic risk score and D:A:D score contributed to CKD. In multivariable analysis, CKD ORs were 2.13 (95% confidence interval, 1.55-2.97) in participants in the 4th (most unfavorable) vs. 1st (most favorable) genetic score quartile; 1.94 (1.37-2.65) in the 4th vs. 1st D:A:D score quartile; and 2.98 (2.02-4.66), 1.70 (1.29-2.29), and 1.83 (1.45-2.40), per 5-years exposure to atazanavir/ritonavir, lopinavir/ritonavir, and tenofovir disoproxil fumarate, respectively. Participants in the 1st genetic score quartile had no increased CKD risk, even if they were in the 4th 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.