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Gross hematuria (GH) is observed shortly after an upper respiratory tract infection in 30–40% of the patients with immunoglobulin A nephropathy (IgAN), however, its mechanism and the renal outcome are unclear. Recently, several reports showed the cases with GH after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with IgAN. Here, we sought to clarify the mechanism of GH in IgAN by detailing the clinical characteristics and measuring serum and urinary galactose-deficient IgA1 (Gd-IgA1), which are known to be associated with development of IgAN, in patients with GH after coronavirus disease 2019 (COVID-19) vaccination. We conducted a multi-center prospective cohort study in Japan.
We analyzed 127 patients who presented with GH after COVID-19 vaccination and conducted a 6-month observational study. Patients, 18 years or older, who presented to the hospital with GH after COVID-19 vaccination were recruited. All the patients visited any of the Japanese hospitals that participated in the prospective observational study between May 11, 2021, and October 31, 2022. We collected the serum and urine samples at the time of the first presentation to the hospital with GH (GH 0) and six months after GH (GH 6). Serum and urine Gd-IgA1 were measured by enzyme-linked immunosorbent assays.
We found that majority of patients who developed GH after COVID-19 vaccination were females (93 patients, 73.2%). GH was observed after the second or subsequent vaccinations in most patients (118 patients, 92.9%). Among the 127 patients, 37 had been already diagnosed with IgAN/ IgA vasculitis (IgAV) and one patient had been diagnosed with PGNMID prior to the vaccination. In remaining 90 patients, 70 who newly underwent kidney biopsy were diagnosed with IgAN (N=67)/IgAV (N=2). Although serum Gd-IgA1 were comparable throughout the observation period (GH 0: 4853.5 ng/mL; interquartile range [IQR] 3887.3-6913.6 ng/mL vs. GH 6: 5343.0 ng/mL; IQR, 4075.0-7063.3 ng/mL; p=0.831), urinary Gd-IgA1 was increased at the time of GH (GH 0: 35.4ng/mL; IQR, 18.4-101.9 ng/mL vs. GH 6: 25.0ng/mL; IQR, 7.5-76.1 ng/mL; p=0.046). These data suggests that deposition of Gd-IgA1 in the glomeruli was enhanced by COVID-19 vaccination by a mechanism other than increasing serum Gd-IgA1.
Present prospective study have shown the clinical characteristics and renal outcome in patients who presented with GH after COVID-19 vaccination. Increased incidence of GH after COVID-19 vaccination in females and after the second or subsequent vaccinations may help to clarify the mechanism of GH in detail. Our study also suggests that GH in IgAN is triggered by some alternations in glomerulus itself that facilitate the deposition of Gd-IgA1.