Gross haematuria after mRNA COVID‐19 vaccination in two patients with histological and clinical diagnosis of IgA nephropathy

A 28 years old lady with history of microscopic haematuria for 5 years underwent a pre‐scheduled kidney biopsy for suspected IgA nephropathy. Her renal function was normal with proteinuria 0.11 g/day. 3 weeks prior to biopsy, she received her second dose of mRNA COVID‐19 vaccine (Pfizer‐BioNTech BNT162b2) and developed painless gross hematuria 3 h later. Serum creatinine level was mildly elevated from 58 to 72 μmol/L. Urine protein creatinine ratio increased from 20 to 320 mg/mmol. Her anti‐nuclear antibody (ANA) turned from negative to positive with a titre of 1: 640, but anti‐dsDNA remained negative. Her C3 and C4 levels were normal. 5 days later, her serum creatinine level fell to 54 μmol/L and hematuria subsided spontaneously. 3 weeks later, her urine protein creatinine ratio fell to 34 mg/mmol and ANA became negative. Kidney biopsy confirmed IgA nephropathy with Oxford classification M1E0S0T0‐C0 without features suggestive of lupus nephritis.

The second patient was a 58 years old lady with hypertension and microscopic haematuria for 1 year. She recalled an episode of painless gross haematuria in 2008. CT urogram and cystoscopy were normal. There were 4% dysmorphic red blood cells in urine. Urine protein creatinine ratio was 24 mg/mmol. IgA nephropathy was suspected clinically. Kidney biopsy was not arranged. 1 day after her second dose of Pfizer‐BioNTech mRNA COVID‐19 vaccine, she developed painless gross haematuria lasting for 2 days. Her serum creatinine level remained stable at 78 μmol/L 3 weeks later.

To date, at least 15 cases of acute flare of IgA nephropathy after COVID‐19 vaccination have been published, involving both the Pfizer‐BioNTech and Moderna mRNA vaccines. All of them had gross haematuria, mostly within 6 to 24 h after the second dose vaccination, with or without increase in proteinuria. Most of them had spontaneous resolution after a few days. Only two patients required steroid therapy for acute kidney injury. ¹ , ² Our first patient had earliest onset of gross haematuria within just 3 h. The transient strongly positive ANA indicates that the COVID‐19 vaccination may trigger more generalized immunological response beyond just stimulating IgA production. Reactivation of and new onset lupus nephritis after COVID‐19 vaccination with elevated ANA titre have also been reported recently, one after mRNA and the other after the AstraZeneca COVID‐19 vaccination. ³ , ⁴ Flare of other glomerulonephritis has also been reported after different types of COVID‐19 vaccination. ⁵ Our second patient reflects that gross haematuria developing shortly after COVID‐19 vaccination may reflect or unmask the presence of pre‐existing IgA nephropathy. As flare of IgA nephropathy after COVID‐19 vaccination is uncommon and mostly benign, it should not be a reason for deterring vaccination. More data on the incidence and significance of acute flare of IgA nephropathy after COVID‐19 vaccination will be very useful.