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.

Dietrich, Léna G; Barceló, Catalina; Thorball, Christian W; Ryom, Lene; Burkhalter, Felix; Hasse, Barbara; Furrer, Hansjakob; Weisser, Maja; Steffen, Ana; Bernasconi, Enos; Cavassini, Matthias; de Seigneux, Sophie; Csajka, Chantal; Fellay, Jacques; Ledergerber, Bruno; Tarr, Philip E (2020). 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 diseases, 70(5), pp. 890-897. Oxford University Press 10.1093/cid/ciz280

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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.

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