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.    Clinical Infectious Disease

In HIV, the relative contribution of genetic background, clinical risk factors, and antiretrovirals to chronic kidney disease (CKD) is unknown.

Dietrich et al. 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 86’613 single nucleotide polymorphisms.

They included
743 cases (79% male; median age, 42 years; baseline eGFR 106 mL/min/1.73 m²) with confirmed eGFR drop <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 4^th (most unfavorable) vs. 1^st (most favorable) genetic score quartile; 1.94 (1.37-2.65) in the 4^th vs. 1^st 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 1^st genetic score quartile had no increased CKD risk, even if they were in the 4^th D:A:D score quartile.

In summary, the genetic score increased CKD risk similar to the clinical D:A:D score and potentially nephrotoxic antiretrovirals. Irrespective of the D:A:D score, individuals with the most favorable genetic background may be protected against CKD.

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