FC008: Sex Difference in COVID-19 Mortality Risk among Patients on Kidney Function Replacement Therapy

Abstract BACKGROUND AND AIMS In the general population with COVID-19, male sex is an established risk factor for mortality. A more robust immune response to COVID-19 in women has been suggested to be one of the factors explaining this sex difference in mortality. Patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants. In this study, we therefore examined whether male sex is still a risk factor for mortality among patients on KFRT with COVID-19. METHOD Data were used from the European Renal Association COVID-19 Database (ERACODA) of kidney transplant recipients and dialysis patients who presented with COVID-19 between 1 February 2020 and 30 April 2021. The primary study outcome was 3-month mortality. As secondary outcomes, in-hospital mortality and 28-day mortality were examined. Associations were investigated using multivariable Cox proportional-hazards regression analysis. Assuming immunosuppressant use is among the main factors contributing to excess mortality in kidney transplant recipients compared with dialysis patients, we also investigated the association of type of KFRT with mortality by sex. RESULTS ERACODA included 1204 kidney transplant recipients (male: 62.0%, mean age: 56.4 years) and 3206 dialysis patients (male: 61.8%, mean age: 67.7 years). 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). In a model adjusted for age, frailty, smoking and comorbidities, the aHR for the risk of 3-month mortality in males (versus females) was 0.87 (95% CI: 63, 1.21, P = 0.41) in kidney transplant recipients and 1.32 (95% CI: 1.13, 1.55, P = 0.001) in dialysis patients (P for interaction = 0.03). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (versus dialysis patients) was 1.26 (95% CI: 1.02, 1.56, P = 0.03) in males and 1.73 (95% CI: 1.31, 2.27, P < 0.001) in females (p for interaction = 0.03). Essentially similar results were obtained for in-hospital mortality and 28-day mortality. CONCLUSION In patients on kidney function replacement therapy with COVID-19, male sex is not a risk factor for mortality among kidney transplant receipts 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.