Kidney Function in IgA Nephropathy Not Impacted by Mild, Moderate COVID-19 Infection

Hong Zhang, MD, PhD

Credit: Michigan Medicine

Findings from a recent study are providing clinicians with an overview of the impact of mild to moderate COVID-19 infection on subsequent kidney function in patients with IgA nephropathy (IgAN).¹

Although results of the retrospective cohort study showed COVID-19 infection did not significantly exacerbate kidney dysfunction in patients with preserved kidney function at baseline, COVID-19 infection was linked to an accelerated rate of kidney function decline in patients with pre-existing reduced renal function, suggesting the need for individualized management based on baseline kidney function status.¹

IgA is a key component of the adaptive immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19.² Although the exact causative pathways are not well understood, COVID-19 infection has been linked to the onset and relapse of various glomerulonephritis conditions, like IgAN.¹

“It is imperative to explore the impact of COVID-19 on pre-existing kidney conditions like IgA nephropathy, which previously demonstrated a correlation with visible hematuria following upper respiratory tract infections,” Hong Zhang, MD, PhD, a professor of internal medicine and director of the renal division at Peking University First Hospital in China, and colleagues wrote.¹ “However, the clinical outcomes for IgA nephropathy post-COVID-19 infection remain uncertain.”

To investigate whether COVID-19 infection exacerbates kidney dysfunction in individuals with IgAN, investigators conducted a single-center retrospective cohort analysis of adult patients >18 years of age with established diagnoses of IgAN based on native kidney biopsy, excluding those who had undergone renal replacement therapy or transplantation, those who discontinued participation in the cohort, and cases of newly diagnosed IgAN concomitant with COVID-19 or following SARS-CoV-2 vaccination.¹

Participants were scheduled for regular in-person consultations at 1- to 6-month intervals, during which estimated glomerular filtration rate (eGFR) based on serum creatinine and 24-hour proteinuria levels were measured. COVID-19 infection status was determined using a questionnaire and the Health Code application, both administered at the end of 2022 in northern China.¹

The primary outcome of interest was eGFR trajectory. Other parameters of interest were change in the absolute eGFR value and change in eGFR slope before and after a time-updated cumulative primary exposure to COVID-19.¹

In total, the study included 199 patients, 75% (n = 181) of whom reported a confirmed SARS-CoV-2 infection with 79% (n = 143) confirmed through testing. The remaining 25% (n = 18) were confirmed to be negative for COVID-19 during the study period through testing.¹

Among the cohort, the median age was 38 years and 45.23% of participants were male. Among the 181 reported positive cases, the majority (98.9%) experienced mild to moderate symptoms, with 2 (1.1%) requiring hospitalization due to lung infection. Investigators noted no severe or critical cases were observed.¹

During a median follow-up of 10.7 months post-COVID-19 infection, notable clinical events included gross hematuria in 30 patients (16.6%), which normalized within an average of 3 days without the need for medical intervention. Additionally, investigators observed a 2-fold increase in proteinuria or progression to the nephrotic range in 10 individuals (5.5%). No cases of acute kidney injury were noted.¹

Upon analysis, COVID-19 exposure was associated with an absolute change in eGFR of 2.98 mL/min/1.73 m2 per month (95% confidence interval [CI], 0.46 to 5.50). However, in a fully adjusted model, the estimated changes in eGFR slope post-COVID-19 were –0.39 mL/min/1.73 m2 per month (95% CI, –0.83 to 0.06; P = .088), which included the possibility of no significant effect. The interactions analysis for eGFR change, particularly between baseline eGFR and COVID-19 exposure status, revealed statistically significant multiplicative effects (adjusted P for interaction = .035).¹

Stratified analysis based on patients’ baseline eGFR levels revealed a greater rate of kidney function decline among patients with eGFR <45 mL/min/1.73 m2, with a rate of decline measured at –0.56 mL/min/1.73 m2 per month (95% CI, –1.11 to –0.01; P = .048). However, in patients with eGFR ≥45 mL/min/1.73 m2, investigators pointed out the presence of COVID-19 infection had no apparent effect on the rate of kidney function decline, as indicated by an estimated change of –0.01 mL/min/1.73 m2 per month (95% CI, –0.57 to 0.59; P = .973).¹

Investigators outlined multiple limitations to these findings, including the potential for memory and reporting biases due to self-reported data; limited statistical power to assess the impact of more severe COVID-19 infections due to most participants having mild infection; and the inability to account for other hemodynamic factors influencing eGFR levels over time.¹

“These findings highlight the critical need for ongoing monitoring and vigilant care for individuals with reduced kidney function,” investigators concluded.¹ “Our study provides valuable insights into the interplay between COVID-19 and IgA nephropathy, emphasizing the necessity for tailored management approaches based on the patient's kidney function status.”

References

1. ^{Hui M, Shi SF, Zhou XJ, et al. The impact of mild and moderate COVID-19 infection on the progression of kidney dysfunction in patients with IgA nephropathy, Clinical Kidney Journal. https://doi.org/10.1093/ckj/sfae157}
2. ^{Tyagi R, Basu S, Dhar A, et al. Role of Immunoglobulin A in COVID-19 and Influenza Infections. Vaccines (Basel). doi:10.3390/vaccines11111647}