A CASE OF IgA NEPHROPATHY EXHIBITING MULTIFACETED RENAL INJURY AFTER REPETITIVE COVID-19 VACCINE–RELATED GROSS HEMATURIA

【Introduction】Following COVID-19 vaccination, several cases of new-onset renal abnormalities have been reported. We describe a severe case of IgA nephropathy who developed multifaceted renal injury in glomeruli, tubulointerstitium and small arteries.

【Case presentation】A 51-year-old woman who exhibited urinary findings of occult blood 2+ without proteinuria at consecutive health examinations from 20 years ago, received two doses of the Pfizer COVID-19 mRNA vaccine in August, year X–3, without any adverse events. However, she repeated gross hematuria after each booster injections in March and November, year X–2, which resolved spontaneously. At the end of December, year X-1, she developed the third episodes of gross hematuria associated with general malaise, and then visited our urology department, on January, year X. Consecutive urinalysis showed occult blood 2+ with dysmorphic RBCs, she was referred to the nephrology division, in April, year X. Serum creatinine (sCr) was 1.00 mg/dL, eGFR 46 mL/min/1.73 m², with serum IgA 238 mg/dL, C3 123 mg/dL and urinary findings of occult blood 3+, sediment RBC>100/HPF, protein 1.86 g/gCr, β₂-microglobulin 3365 μg/L and N-acetyl-β-D-glucosaminidase 25.1 U/L.

A renal biopsy was performed in May, year X, by surgical open biopsy because of too skinny figure. Light microscopy revealed 134 glomeruli, of which 18% were globally sclerotic. Mesangial matrix expansion and mesangial cell proliferation were observed in 28% glomeruli. Most glomeruli showed collapse of the capillary loops and swelling of endothelial cells and podocytes. In small arteries and arterioles an increase in smooth muscle cells with narrow space was observed without hyalinosis or fibrous thickening, suggesting vasculitis rather than arteriosclerosis. The tubulointerstitial area showed patchy inflammatory cell infiltration predominantly by lymphocytes. Electron microscopy showed swollen glomerular endothelial cells and wrinkling glomerular basement membrane. Electron-dense deposits were observed in the mesangial regions and partly in subepithelial and subendothelial basement membrane. Immunofluorescence demonstrated granular deposits of IgA and C3 in the mesangial and paramesangial area. Immunoenzyme staining with anti-CD34 antibody reactive against an endothelial antigen revealed granular perinuclear pattern suggesting collapsed glomerular capillaries in the most glomeruli. These findings indicated IgA nephropathy associated with collapsing glomerulopathy, tubulointerstitial nephritis, and small-vessel arteritis.

She declined glucocorticoid or immunosuppressive therapy. A sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin was administered. After one year, her renal function was maintained at sCr 0.85 mg/dL, with urinary protein 0.75 g/gCr and sediment RBC>30-39/HPF.

【Discussion and Conclusion】In this case, urinary abnormalities were minimal before vaccination. However, they worsened rapidly after repetitive booster injections. Renal biopsy revealed several acute-phase lesions, including glomerular endothelial swelling, capillary collapse, tubulointerstitial nephritis, and small-vessel arteritis. These findings suggest that vaccine-induced immune and inflammatory activation might have triggered endothelial injury leading to multifaceted pathological process in a patient with subclinical IgA nephropathy. This abstract was also submitted for the 55th Western Regional Meeting of the Japanese Society of Nephrology.