Patients with primary glomerular disease who have COVID-19 face increased risk for severe adverse outcomes, including hospitalization, kidney replacement therapy (KRT), or death. Risk factors in that patient population include a higher prevalence of hypertension and diminished kidney function. Patients with glomerular disease are often treated with immunosuppression, which has been linked to attenuated response to COVID-19 vaccines, resulting in blunting the effectiveness of vaccines in mitigating COVID-19.
There are concerns that COVID-19 may exacerbate glomerular disease and kidney function decline. In addition, acute kidney injury from severe COVID-19 is common among patients with glomerular disease and may increase the risk of kidney failure. There have also been reports of disease relapse after COVID-19 vaccination among patients with glomerular disease, which may result in vaccine hesitancy.
Chia-shi Wang, MD, MSc, and colleagues conducted a study designed to examine the association of COVID-19 versus COVID-19 vaccination with kidney function and glomerular disease activity. Results of the study were reported in the American Journal of Kidney Diseases.
The National Institutes of Health-sponsored Cure Glomerulonephropathy (CureGN) observational cohort study included 71 centers and more than 2500 patients in the United States, Canada, and Europe with primary minimal change diseases, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy. The study exposures were COVID-19 and COVID-19 vaccination.
The primary outcomes of interest were decline in estimated glomerular filtration rate (eGFR) and glomerular disease activity based on the degree of proteinuria. Worsening of glomerular disease was defined by doubling of the urinary protein-creatinine ratio (UPCR) to at least 1.5 g/g or increase in dipstick urine protein by two ordinal levels to 3+ (300 mg/dL) or above.
CureGN participants had study visits and data collection on COVID-19 and vaccination from July 1, 2021, to January 1, 2023. The median number of completed study visits per person with information on COVID-19 and vaccination was three. The overall cohort included 2055 participants. Of those, 44% (n=900) were female, and 72% (n=1477) had at least one comorbidity (52% hypertension [n=1056], 6% diabetes mellitus [n=129], 14% cardiovascular disease [n=278], 16% asthma/chronic obstructive pulmonary disease [n=335], 9% cancer [n=189], and 35% obesity [n=715]).
Thirty-five percent of participants (n=722) experienced COVID-19 infection, resulting in an incidence rate of 15.2 per 100 person-years since January 1. 2020. Patterns of first incidence of COVID-19 infection were similar between the CureGN cohort and US trends.
Of the 722 participants with COVID-19 infection, 13% (n=90) were hospitalized, including five who were admitted to the intensive care unit, and three died. One participant required acute KRT. Eight patients progressed to kidney failure after COVID-19 (median time of 322 days). Of those eight patients, seven were unvaccinated at the time of their COVID-19 episode.
Among the CureGN cohort, 68% (n=1407) reported receiving at least one COVID-19 vaccine. The proportion of vaccinated individuals remained relatively constant since the summer of 2021; the lowest uptake was among pediatric subgroups. By January 1, 2023, 65% of participants in the CureGN cohort were fully vaccinated against COVID-19.
Of the 722 participants in the CureGN cohort who developed COVID-19, 232 had at least two eGFR measurements prior to their illness and two after their illness. Follow-up was a median of 3.67 years prior to illness and 0.84 years after. The slope of eGFR prior to COVID-19 was –1.40 mL/min/1.73 m2 per year (calculated based on a median of 13 measurements).
Following COVID-19 infection, slopes were calculated based on a median of three eGFR measurements. At 6 months post COVID-19, the eGFR slope was –4.26 mL/min/1.73 m2 per year (the difference was not statistically significant from before COVID-19 infection). There were no statistically significant differences in slopes between patients who were vaccinated at the time of COVID-19 infection and those who were not vaccinated at the time of infection.
A total of 583 participants who experienced COVID-19 infection had at least two urine protein or dipstick measurements before and after their illness. Comparing glomerular disease activity between those who experienced
COVID-19 and matched controls who did not experience COVID-19, there was an association between COVID-19 infection and subsequent worsening in glomerular disease (hazard ratio [HR], 1.35; 95% CI, 1.01-1.80; P=.04).
Of the 1407 CureGN cohort participants who received a COVID-19 vaccination, 705 had at least two eGFR measurements before and two after their illness. Median follow-up was 3.59 years before and 1.33 years after vaccination. There was no association between COVID-19 vaccination and decline in eGFR.
There were 1129 participants with at least two urine protein or dipstick measurements before and after COVID-19 vaccination. In comparisons of those who received a COVID-19 vaccine with matched controls who did not receive a vaccine, there was no association between vaccination and higher risk of subsequent worsening in glomerular disease (HR, 1.02; 95% CI, 0.79-1.33; P=.87). Further, there were no significant differences in worsening of glomerular disease between patients who were vaccinated at the time of their COVID-19 infection and those who were not vaccinated at the time of the infection.
Citing limitations to the study findings, the authors included incomplete sampling of CureGN participants (2055 of 2698 total participants), reliance on self-report and review of electronic health records for identification of cases of COVID-19, and the relatively short follow-up period, making associations with eGFR and glomerular disease activity among those with COVID-19 infection unclear.
In conclusion, the researchers said, “COVID-19 occurred commonly and was often severe in patients with primary [glomerular disease] from the CureGN cohort. COVID-19 infection [was] also associated with a higher risk of increased [glomerular] disease activity as defined by proteinuria. By contrast, COVID-19 vaccination was not associated with [glomerular] disease activity. Strategies to promote COVID-19 vaccination are critical to prevent COVID-19 infection and its major sequelae, including [glomerular disease] relapse and decline in kidney function.”
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