Dietrich, Léna G; Thorball, Christian W; Ryom, Lene; Burkhalter, Felix; Hasse, Barbara; Thurnheer, Maria Christine; Weisser, Maja; Schmid, Patrick; Bernasconi, Enos; Darling, Kathrine E A; Buvelot, Hélène; Fellay, Jacques; Ledergerber, Bruno; Tarr, Philip E (2021). Rapid Progression of Kidney Dysfunction in Swiss People Living with HIV: Contribution of Polygenic Risk Score and D:A:D Clinical Risk Score. The journal of infectious diseases, 223(12), pp. 2145-2153. Oxford University Press 10.1093/infdis/jiaa695
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BACKGROUND
In people with HIV (PWH), it is unknown whether genetic background associates with rapid progression of kidney dysfunction; i.e. eGFR decrease of >5mL/min/1.73m 2 per year for >3 consecutive years.
METHODS
We used time-to-event analyses to measure univariable and multivariable hazard ratios (HR) for rapid progression, based on the clinical D:A:D CKD risk score, antiretroviral exposures, and a polygenic risk score based on 14'769 genome-wide single nucleotide polymorphisms (SNPs) in white Swiss HIV Cohort Study participants.
RESULTS
We included 225 participants with rapid progression (median age 42 years, 76% male, median baseline eGFR 101 mL/min/1.73m 2) and 3378 rapid progression-free participants. In multivariable analysis, compared to participants with a low risk D:A:D CKD risk score, participants with medium and high risk had rapid progression-HR=1.30 (0.99-1.71) and 1.82 (1.28-2.60), respectively. Compared to the first (most favorable) polygenic risk score quartile, participants in the second, third and fourth (most unfavorable) quartiles had rapid progression-HR=1.39 (0.94-2.06), 1.52 (1.04-2.24) and 2.04 (1.41-2.94), respectively. Recent exposure to tenofovir disoproxil fumarate was associated with rapid progression (HR=1.36 [1.06-1.76]).
DISCUSSION
An individual polygenic risk score is associated with rapid progression in Swiss PWH, when analyzed in the context of clinical and antiretroviral risk factors.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology |
UniBE Contributor: |
Thurnheer Zürcher, Maria Christine |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1537-6613 |
Publisher: |
Oxford University Press |
Language: |
English |
Submitter: |
Annelies Luginbühl |
Date Deposited: |
07 Dec 2020 11:39 |
Last Modified: |
05 Dec 2022 15:41 |
Publisher DOI: |
10.1093/infdis/jiaa695 |
PubMed ID: |
33151293 |
Uncontrolled Keywords: |
HIV infection antiretroviral therapy clinical risk factors genetics rapid progression of kidney disease |
BORIS DOI: |
10.7892/boris.147934 |
URI: |
https://boris.unibe.ch/id/eprint/147934 |
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