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. 2022 Oct 26;12(1):17978.
doi: 10.1038/s41598-022-22657-4.

Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy

Priya Vart  1   2 , Raphaël Duivenvoorden  3 , Aaltje Adema  4 , Adrian Covic  5   6 , Patrik Finne  7 , Nicole Heijtink-Ter Braak  8 , Kaisa Laine  9 , Marlies Noordzij  10 , Marcel Schouten  11 , Kitty J Jager  12   13 , Ron T Gansevoort  10 ; ERACODA Collaborators
Collaborators, Affiliations

Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy

Priya Vart et al. Sci Rep. .

Abstract

In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Percentage mortality by sex and type of kidney function replacement therapy (A) and hazard ratio for the association of sex (male vs. female (reference)) with 3-month mortality by type of kidney function replacement therapy (B). *Adjusted for: age (continuous), clinical frailty score (continuous), the reason for COVID-19 screening (symptoms-based screening, positive COVID-19 contact or routine screening), smoking (never, current, former), obesity (yes/no), hypertension (yes/no), diabetes (yes/no), heart failure (yes/no), chronic lung disease (yes/no), coronary artery disease (yes/no), and auto-immune disease (yes/no), duration of kidney function replacement therapy (years) and estimated glomerular filtration rate (continuous). †Adjusted estimate from literature (Nat Commun 2020: https://pubmed.ncbi.nlm.nih.gov/33298944/).
Figure 2
Figure 2
Association of sex with 3-month mortality in kidney transplant recipients (A) and dialysis patients (B) with COVID-19 by key subgroups (presented are hazard ratios for male versus female with 95% confidence intervals, and p-values for interaction).
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