Gross Hematuria After COVID Vaccination Linked to Short-Term Kidney Function Decline in IgAN

New research is shedding light on increases in short-term kidney function decline following post-COVID-19 vaccination gross hematuria (GH) in individuals with IgA nephropathy (IgAN).1

Leveraging data from 4 medical centers in Japan, the study found greater short-term decline in kidney function for approximately 1 year after vaccination, even after adjustment for potential confounding factors such as age, sex, duration of IgAN, baseline kidney function, and treatments, including RAASi, corticosteroids, and tonsillectomy. Of note, as follow-up duration increases, differences in kidney function decline lost significance.1

“To our knowledge, this is the first study to specifically evaluate the association of post-COVID-19 mRNA vaccination GH in IgAN, with a focus on longitudinal eGFR changes,” Shinya Yokote, MD, PhD, of Jikei University School of Medicine, and colleagues wrote.1 “Using a real-world cohort, we provide novel insights into the clinical relevance of post-vaccination GH and its temporal association with kidney function trajectory.”

A growing body of research points to acute kidney injury accompanied by GH following COVID-19 mRNA vaccination in individuals with IgAN. A 2024 study found that female patients and patients with IgAN and IgA vasculitis are more likely to experience GH following COVID vaccination, especially after the second and third doses.2

To assess the effect of post-vaccination GH on kidney function in patients with IgAN, investigators recruited outpatients with biopsy-proven IgAN from Jikei University Hospital, Jikei Katsushika Medical Center, Jikei Kashiwa Hospital, or Jikei Daisan Hospital between February 2021 and September 2022.1

A total of 441 patients were included in the study. Among the cohort, the median age was 51 (interquartile range [IQR], 42 to 62) years, the majority (56%) of patients were female, and the median duration of IgAN was 12 (IQR, 5 to 21) years.1

Investigators classified participants into 3 groups: unvaccinated (n = 25), vaccinated without GH (n = 391), and vaccinated with GH (n = 25). Their kidney function was evaluated at approximately 1 year (midpoint) and 2 years (endpoint) after baseline.1

Compared with those in the other 2 groups, investigators noted patients in the vaccinated with GH group were significantly younger (P <.05), more likely to be female (P <.05), had a shorter history of IgAN (P <.05), higher eGFR values (P <.05), and more frequent episodes of microscopic hematuria (P <.001). Additional treatments following vaccination, such as corticosteroid therapy or tonsillectomy, were significantly more common in the vaccinated with GH group than in the other 2 groups.1

At 1 year follow-up, the annual change in eGFR (ΔeGFR) was − 1.16, − 1.03, and − 2.50 mL/min/1.73 m²/year in the unvaccinated, vaccinated without GH, and vaccinated with GH groups, respectively, with significantly lower values in the GH group than in the no-GH group (P = .015). Similarly, the corresponding percentage change in eGFR (ΔeGFR%) was − 2.81, − 1.90, and − 4.66%/year, and was significantly lower in the GH group than in the no-GH group (P = .048).1

Multivariable analysis revealed post–COVID-19 GH (odds ratio [OR], 2.97; 95% CI, 1.06 to 8.30; P = .038), baseline eGFR ≥ 60 (OR, 1.84; 95% CI, 1.12 to 3.05; P = .017), and UPCR ≥ 0.3 g/g (OR, 2.03; 95% CI, 1.26 to 3.27; P = .003) were independently associated with eGFR decline. Additionally, linear regression analysis revealed GH was significantly associated with ΔeGFR at 1 year in both univariable and multivariable models (β = − 3.326; P <.0001 and β = − 2.878; P = .003)1

At 2 years of follow-up, the ΔeGFR was − 0.45, − 1.93, and − 1.72 mL/min/1.73 m²/year in the unvaccinated, vaccinated without GH, and vaccinated with GH groups, respectively, with no significant differences observed between the groups. Similarly, the ΔeGFR% was − 1.81, − 3.44, and − 2.65%/year, again without significant differences.1

“In this cohort, GH after vaccination was observed to be associated with a greater short-term decline in kidney function, without evidence of a sustained difference in long-term trajectories,” investigators concluded.1 “These observational findings should be considered hypothesis-generating and do not directly inform vaccination or treatment policies. Larger multicenter prospective studies with adjudicated endpoints are required to determine whether any causal relationships exist.”

References

1. Yokote S, Okabe M, Shimizu A, et al. Gross hematuria after COVID-19 mRNA vaccination and kidney function trajectory in IgA nephropathy. Sci Rep. 2025;15(1):35169. doi:10.1038/s41598-025-19068-6

2. Brooks A. Gender, IgA Nephropathy Linked to Gross Hematuria After COVID-19 Vaccination. HCPLive. October 3, 2024. Accessed October 9, 2025. https://www.hcplive.com/view/gender-iga-nephropathy-linked-gross-hematuria-after-covid-19-vaccination