Using genetics to understand the role of kidney function in COVID-19: a mendelian randomization study

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Jie V Zhao1, C Mary Schooling2,3

  • 1School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 1/F, Patrick Manson Building, 7 Sassoon Road, Hong Kong, SAR, China. janezhao@hku.hk.

BMC Nephrology
|November 14, 2021
PubMed

Insights

Better kidney function, indicated by higher estimated glomerular filtration rate (eGFR), is linked to a reduced risk of severe COVID-19. This suggests kidney function is a potential therapeutic target for COVID-19 treatment.

Area of Science:

  • Genetics
  • Nephrology
  • Infectious Diseases

Background:

  • Kidney dysfunction is a known predictor of mortality in severe COVID-19.
  • The causal relationship between kidney function and severe COVID-19 has been unclear due to confounding in observational studies.
  • Mendelian randomization is employed to investigate the unconfounded role of kidney function in severe COVID-19.

Purpose of the Study:

  • To determine if impaired kidney function is a cause or symptom of severe COVID-19.
  • To assess the causal effect of genetically predicted kidney function on severe COVID-19 risk.
  • To explore the association between kidney function and COVID-19 hospitalization and infection.

Main Methods:

  • Utilized genome-wide significant, uncorrelated genetic variants to predict kidney function (eGFR and UACR).
  • Employed Mendelian randomization to analyze the association between genetically instrumented kidney function and severe COVID-19.
  • Examined large cohorts for severe COVID-19 (8,779 cases, 1,001,875 controls), COVID-19 hospitalization (24,274 cases, 2,061,529 controls), and all COVID-19 (112,612 cases, 2,474,079 controls).

Main Results:

  • Genetically predicted higher eGFR was associated with a reduced risk of severe COVID-19 (OR 0.90, 95% CI 0.83-0.98).
  • No significant association was found between genetically predicted higher eGFR and COVID-19 hospitalization or infection.
  • Genetically predicted lower UACR (better kidney function) showed no significant association with COVID-19 outcomes.

Conclusions:

  • Kidney function emerges as a significant factor and potential therapeutic target in severe COVID-19.
  • Medications that improve kidney function, such as antihypertensives, may offer benefits for COVID-19 treatment.
  • Findings support drug repositioning strategies targeting kidney function for COVID-19 management.
Abstract

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