IgA Nephropathy Among Most Common COVID-19 Vaccine-Associated Glomerular Diseases

Findings from a recent study are providing novel insight into glomerular disease following COVID-19 vaccine administration, or highly suspected COVID-19 vaccine-associated glomerular disease.¹

In the study, the majority of CVAGD cases were diagnosed as immunoglobulin A nephropathy (IgAN) and were observed following receipt of 3 common COVID-19 vaccines. Results showed most patients experienced improvements in renal function after receiving treatment, although no patients with antineutrophil cytoplasmic antibody (ANCA)-related rapidly progressive glomerulonephritis (RPGN) achieved full recovery.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. The exact causative pathways are not well understood, but COVID-19 infection has been linked to the onset and relapse of various glomerulonephritis conditions, like IgAN. Recent research has linked COVID-19 infection to an accelerated rate of kidney function decline in patients with IgAN and pre-existing reduced renal function, but the link between IgAN and COVID-19 vaccination is not well understood.^1,2

“With the increased administration of COVID-19 mRNA vaccines (Moderna mRNA-1273 and BioNTech BNT162b2), more and more emerging cases of de novo and relapse of pre-existing glomerular disease have been reported,” Cheng-Hsu Chen, PhD, director of basic medical sciences in the department of medical research at Taichung Veterans General Hospital, and colleagues wrote.¹ “Therefore, the close monitoring and reporting of CVAGD cases are essential.”

To do so, investigators collected data from patients who underwent renal biopsy at Taichung Veterans General Hospital, the leading renal biopsy institution in Taiwan, between June 2021 and October 2022. All participants included in the present study had no previous history of primary or secondary glomerular disease prior to the renal biopsy. Cases deemed to be unrelated to vaccination were excluded, as were renal transplant recipients. Cases of CVAGD, defined as renal biopsy-proven glomerular disease occurring after the onset of symptoms and signs, were collected for further analysis.¹

For COVID-19 vaccination, investigators collected information on all brands of COVID-19 vaccines received prior to renal biopsy, including mRNA vaccines (Moderna mRNA-1273 and BioNTech BNT162b2) and viral vector-based COVID-19 vaccines (Oxford-AstraZeneca ChAdOx1-S). They recorded any symptoms or signs before renal biopsy, the duration between vaccination and the onset of symptoms, the duration between the first vaccination and renal biopsy, and the number of vaccinations received per person.¹

A total of 286 patients underwent renal biopsy, 106 of whom were excluded due to undergoing renal biopsy prior to receiving the COVID-19 vaccine or not receiving the vaccine. Additionally, 129 patients were excluded based on apparent non-vaccine-related indications for renal biopsy as documented in the medical record, including pain-killer-related (n = 29), underlying lupus nephritis (n = 60), and renal transplant (n = 40). In total, 14 eligible patients were identified and enrolled in the study for further analysis.¹

Among the cohort, the median age was 50 years, 42.9% of patients were male, and pre-existing chronic conditions before renal biopsy were not common: 14.3% had diabetes mellitus, 14.3% had hypertension, 14.3% had hyperlipidemia, 21.4% had chronic kidney disease, and 7.1% had coronary artery disease.¹

Investigators noted all 14 patients exhibited proteinuria, defined as daily urine protein levels > 150 mg/day or a urinary protein-to-creatinine ratio (UPCR) > 150 mg/g, and hematuria, defined as the presence of ≥ 3 RBCs per high-power field in a spun urine sediment. The median UPCR was 2012.1 (941.85–3884.1) mg/g and the median urine albumin-to-creatinine ratio (UACR) was 1789.2 (894.35–3158.33) mg/g. Renal function was impaired, with a serum creatinine level of 1.71 (0.79–5.35) mg/dL and a 24 h creatinine clearance of 79.3 (11.13–103.16) mL/min.¹

The majority of CVAGD cases were diagnosed as IgAN (35.7%) followed by ANCA-related RPGN (28.6%). Investigators pointed out minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MN), and lupus nephritis were less common.¹

Among the 14 patients, a total of 28 doses of COVID-19 vaccines were administered. Looking at the closest vaccine to the biopsy date, 35.7% of patients received ChAdOx1-S, 42.9% received Moderna mRNA-1273, and 21.4% received BioNTech BNT162b2. The mean duration from vaccination to the onset of symptoms was 55 (Interquartile range, 2-90) days.¹

Investigators noted most patients experienced improvements in renal function, including reductions in serum creatinine and UPCR, after receiving timely treatment. However, some patients did not show any recovery, including 2 patients with P-ANCA RPGN and 1 with IgAN.¹

Investigators acknowledged multiple limitations to these findings, including the weak correlation between vaccine administration and the development of glomerulopathy; the limited number of cases in the study; and the underdiagnosis of CVAGD.¹

“The most commonly reported cases of CVAGD were associated with IgA nephropathy and ANCA-related RPGN,” investigators concluded.¹ “It is essential to recognize that all types of vaccines pose a risk for CVAGD. However, when RPGN is not present, the outcomes are generally favorable with timely diagnosis and treatment.”

References

1. ^{Chen CH, Chiu YW, Chen BD, et al. De Novo Biopsy-Proven Glomerular Disease Following COVID-19 Vaccination. Journal of Clinical Medicine. https://doi.org/10.3390/jcm13154494}
2. ^{Brooks, A. Kidney Function in IgA Nephropathy Not Impacted by Mild, Moderate COVID-19 Infection. HCPLive. August 7, 2024. Accessed August 28, 2024. https://www.hcplive.com/view/kidney-function-iga-nephropathy-not-impacted-mild-moderate-covid-19-infection}