Impaired kidney function biomarkers and risk of severe COVID‐19: Analysis of population‐based cohort data

BACKGROUND: Patients with impaired kidney function were found at a high risk of COVID‐19 hospitalization and mortality in many observational, cross‐sectional, and hospital‐based studies, but evidence from large‐scale prospective cohorts has been lacking. We aimed to examine the association of kidney function‐related biomarkers and their genetic predisposition with the risk of developing severe COVID‐19 in population‐based data. METHODS: We analyzed data from UK Biobank to examine the prospective association of abnormal kidney function biomarkers with severe COVID‐19, defined by laboratory‐confirmed COVID‐19 hospitalizations. Using genotype data, we constructed polygenic risk scores (PRS) to represent an individual's overall genetic risk for these biomarkers. We also identified tipping points where the risk of severe COVID‐19 began to increase significantly for each biomarker. RESULTS: Of the 502,506 adults, 1650 (0.32%) were identified as severe COVID‐19, before August 12, 2020. High levels of cystatin C (OR: 1.3; 95% CI: 1.2–1.5; FDR = 1.5 × 10(−5)), serum creatinine (OR: 1.7; 95% CI: 1.3–2.1; p = 3.5 × 10(−4); FDR = 3.5 × 10(−4)), microalbuminuria (OR: 1.4; 95% CI: 1.2–1.6; FDR = 4 × 10(−4)), and UACR (urinary albumin creatinine ratio; OR: 1.4; 95% CI: 1.2–1.6; p = 3.5 × 10(−4); FDR = 3.5 × 10(−4)) were found significantly associated with severe COVID‐19. Individuals with top 10% of PRS for elevated cystatin C, urate, and microalbuminuria had 28% to 43% higher risks of severe COVID‐19 than individuals with bottom 30% PRS (p < 0.05). Tipping‐point analyses further supported that severe COVID‐19 could occur even when the values of cystatin C, urate (male), and microalbuminuria were within their normal value ranges (OR >1.1, p < 0.05). CONCLUSIONS: Findings from this study might point to new directions for clinicians and policymakers in optimizing risk‐stratification among patients based on polygenic risk estimation and tipping points of kidney function markers. Our results call for further investigation to develop a better strategy to prevent severe COVID‐19 outcomes among patients with genetic predisposition to impaired kidney function. These findings could provide a new tool for clinicians and policymakers in the future especially if we need to live with COVID‐19 for a long time.