Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathy

To the editor:

After the publication of the 2 letters by Negrea and Rovin¹ and Rahim et al.,² we herein describe 3 additional patients with IgA nephropathy (IgAN) who developed gross hematuria after receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA-based vaccines. The clinical data of our cases are summarized in Table 1 . In line with the 3 previously reported cases, patient 1 had normal kidney function. However, patients 2 and 3 were treated with kidney transplantation (KT) and hemodialysis, respectively. Notably, gross hematuria developed as early as after the first vaccine dose in patients 1 and 2. Additionally, gross hematuria in patient 1 relapsed after the second vaccine dose. Gross hematuria was sporadically accompanied by increased proteinuria, arthralgia, abdominal pain, and urticaria. Serum creatinine also transiently increased in patient 2. Symptoms spontaneously regressed in all the 3 cases. The apparent exacerbation of IgAN in patient 2 occurred in the absence of an anti–SARS-CoV-2 antibody response. Out of a total of 726 KT recipients, we examined the tolerability of 2 doses of the Moderna vaccine in 80 recipients with IgAN. No additional cases of gross hematuria were identified. Seventy patients had available data on anti–SARS-CoV-2 antibodies 1 month after the second dose, and positive serology was identified in 32 cases (45.7%). This finding is in accordance with our previous data.³

Table 1.

Patient demographics and clinical characteristics

Patient no.	Age, yr	Sex	Year of biopsy-proven IgAN diagnosis	Treatment	GFR (ml/min per 1.73 m2) or renal treatment	Episodes of gross hematuria during the disease course	Persistent microscopic hematuria	Proteinuria in 2020, UPR, g/g	Vaccine name	Timing of gross hematuria occurrence after vaccination	Associated symptoms	Proteinuria after the first dose, g/g	GFR 1 mo after the second dose, ml/min per 1.73 m2	Proteinuria 1 mo after the second dose	Anti-spike IgG antibody titers (AU/ml) measured 1 mo after the injection
1	22	M	2019 (IgA vasculitis)	Steroids for 6 mo followed by RAASi	89	No	Yes	0.20	mRNA-1273 (Moderna)	D2 and D25 after the first dose, D2 after the second dose	Arthralgia, transient proteinuria (3 g/g)	0.34	107	0.40	NA
2	41	F	2005	Tac, MPA, and steroids for KT	KT as of 2013	Yes	Yes	0	BNT162b2 (Pfizer)	D2 after the first dose (the patient refused the second dose)	Marked leukocytosis	0.47	57	0.41	14.9a
3	27	F	2020	Steroid for 1 mo followed by RAASi	HD since 1 yr	No	No	20	BNT162b2 (Pfizer)	D2 after the second dose	Abdominal pain, urticaria at D5, moderate pancytopenia	1.9	NA	1.2	>250b

AU, arbitrary unit; D, day; GFR, glomerular filtration rate; HD, hemodialysis; IgAN, IgA nephropathy; KT, kidney transplantation; MPA, mycophenolic acid; NA, not available; RAASi, renin-angiotensin-aldosterone system inhibitor; Tac, tacrolimus; UPR, urine protein-to-creatinine ratio.

^aSerology assessment performed 1 mo after the first vaccine dose using the ARCHITECT IgG II Quant test (Abbott). Titers >50 AU/ml were considered positive (detection range, 6.8–80,000 AU/ml).

^bSerology assessment performed 1 mo after the second vaccine dose using the Elecsys Anti-SARS-CoV-2 S (Roche). Titers >0.8 U/ml were considered positive (detection range, 0.8–250 U/ml).

In summary, gross hematuria can occur even after the first vaccine dose and it can also affect—albeit rarely—KT recipients with IgAN. This event seems unrelated to the anti-SARS-CoV-2 antibody response. Patients with IgAN should be thoroughly followed up to shed more light on this potential adverse event.