Gross Hematuria after the COVID-19 mRNA Vaccination: Nationwide Multicenter Prospective Cohort Study in Japan

Abstract

Key Points Little is known about the clinicopathological characteristics and renal outcomes in the patients with gross hematuria (GH) after the vaccination. To fill a clinicopathological knowledge gap regarding vaccination and GH, we conducted a nationwide multicenter prospective cohort study. GH is more likely to occur in patients with IgA nephropathy, with a female bias, but without progressive exacerbation of renal function. Background In the past 3 years, cases of gross hematuria (GH) after the vaccination for coronavirus disease 2019 in patients with IgA nephropathy (IgAN) have been frequently reported worldwide. However, the postevent renal prognosis of these patients, their clinical backgrounds, and underlying mechanisms remain unknown. Therefore, we conducted a nationwide multicenter prospective cohort study in Japan. Methods We analyzed laboratory findings at the time of the first presentation to the hospital and 3 and 6 months after in patients with GH after the vaccination and histopathological findings in their kidney biopsy specimens. Moreover, changes in pathological biomarkers of IgAN such as galactose-deficient IgA1 (Gd-IgA1) and its immune complexes were also evaluated. Results During the study period, 127 newly presenting patients with GH after the vaccination were enrolled, with a clear female bias (73.2%). GH was observed after the second or subsequent vaccinations in most patients (92.9%). Of the 37 patients undergoing kidney biopsy before the vaccination, 36 patients had been diagnosed with IgAN/IgA vasculitis (IgAV). In the remaining 90 patients, 69 of the 70 who newly underwent kidney biopsy were diagnosed with IgAN ( n =67)/IgAV ( n =2). Their histopathology did not show a high incidence of acute lesions such as endocapillary hypercellularity and crescentic lesions. Most cases showed a temporary increase in proteinuria, but no sustained worsening in renal function. Among the biomarkers measured, serum Gd-IgA1 and immune complexes were comparable throughout the observation period; however, only urinary Gd-IgA1 was increased at the time of GH. Conclusions We found that GH after the vaccination is more likely to occur in patients with IgAN/IgAV, with a female bias, but without progressive exacerbation of renal function. Although further investigation is needed regarding causal relationship between vaccination and GH, this study provides many insights into the molecular mechanisms of GH.