Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA

Abstract

Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death [adjusted hazard ratio (aHR) 0.89], but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31-1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.

Keywords: COVID-19; chronic kidney disease; mortality; prevalence; renal replacement therapy; risk factor.

FIGURE 1

Global prevalence of key underlying conditions associated with severe COVID-19 if infected. Prevalence by age. The four most prevalent risk factors have been selected and ranked from left to right according to the highest global prevalence at any age range (bold black line). Grey lines represent individual countries. Data from Clark et al. [5].

FIGURE 2

Risk factors for COVID-19-related death. Graph shows the five medical conditions associated with the highest HRs of death and, additionally, the risk associated with CKD G3 and the risk associated with the risk factors recognized early in the pandemic as associated with severe COVID-19 (diabetes, chronic heart disease and hypertension, in black). In red, conditions of nephrological interest. Light blue represents non-kidney risk factors present in <100 individuals. Data derived from Williamson et al. [4]. Patients with CKD G4–G5 have an eGFR <30 mL/min/1.73 m² and patients with CKD G3 have an eGFR of 30–60 mL/min/1.73 m².

FIGURE 3

CKD as a risk factor for COVID-19-related death in T1DM and T2DM patients in general practice. (A) The aHRs for COVID-19-related death according to type of diabetes and eGFR range. (B) The aHRs for COVID-19-related death according to type of diabetes, age and eGFR range. An eGFR ≥90 mL/min/1.73 m² was the reference for both graphs and was considered to be 1 in each of the categories (T1DM, T2DM and age categories within) assessed. *P < 0.0001 versus eGFR ≥90 mL/min/1.73 m²; +, non-overlapping 95% CI versus eGFR ≥90 mL/min/1.73m². Data derived from Holman et al. [20].

FIGURE 4

Risk factors for COVID-19-related death. Left graph shows the situation in subjects of the general population (as derived from the OpenSAFELY study; data from Williamson et al. [4]) and the right graph shows the situation in patients with end-stage kidney disease treated by maintenance haemodialysis (as derived from the ERACODA cohort; data derived from Hilbrands et al. [23]).