Safety Evaluation of COVID-19 Vaccine in Patients With IgA Nephropathy or IgA Vasculitis Nephritis.

To the Editor:

IgA nephropathy (IgAN) is the most commonly reported glomerulonephritis associated with COVID-19 vaccine., As an immunostimulant, safety is the principal concern of patients with IgAN. Lim et al. reported that no patient experienced gross hematuria and serum creatinine level of a few patients rose slightly. However, the vaccine type was restricted to mRNA vaccine and the sample size was small. Thus, the safety of COVID-19 vaccine in the population of IgAN still needs to be fully explored.

We retrospectively investigated 965 patients with IgAN or IgA vasculitis nephritis, and 46% (443 of 965) of the patients received at least 1-dose vaccination (Supplementary Figure S1). Of these, 76 patients vaccinated before kidney biopsy were excluded. Finally, 367 vaccinated patients were included for primary safety evaluation. Most (351 of 367, 96%) patients were injected an inactivated vaccine (CoronaVac or BBIBP-CorV).

There were 2 (0.5%, 95% CI, 0.07%–2.0%) flare-up events reported by patients and adjudicated. After 2 weeks from receiving the first dose, 1 patient experienced gross hematuria episode. Another developed nephrotic syndrome, 3 months after the second dose. The 2 patients started or escalated their immunosuppressive therapy after exacerbation. Further analysis revealed that 3 patients exhibited >30% estimated glomerular filtration rate decrease and 3 patients progressed to nephrotic proteinuria within 3 months. Overall, 6 (1.6% [0.6%–3.5%]) composite kidney adverse events were adjudicated (Table 1). The subsequent change of these patients was displayed in Supplementary Figure S2.

Table 1

The characteristics of the patients developing kidney adverse events

Patient	Age/Sex	Vaccine	Baseline			Postvaccination
			eGFR, ml/min per 1.73 m2	Proteinuria, g/d	IS
1	32/F	CoronaVac	108	0.35	No	Gross hematuria 2 wk later; received immunosuppressive therapy.
2	40/F	CoronaVac	90.1	1.04	No	>30% eGFR decline within 3 mo.
3	35/F	CoronaVac	63.8	0.09	Yes	>30% eGFR decline; progressed to nephrotic syndrome within 3 mo;adjusted immunosuppressive regime.
4	36/M	CoronaVac	66.3	0.73	Yes	>30% eGFR decline within 2 mo.
5	36/M	CoronaVac	61.2	2.28	No	Progressed to nephrotic proteinuria within 3 mo.
6	37/F	BBIBP-CorV	25.2	1.14	No	Progressed to nephrotic proteinuria within 2 mo.

eGFR, estimated glomerular filtration rate; F, female; IS, immunosuppressants; M, male.

Furthermore, 202 patients received blood and urine tests within 3 months before and after vaccination were available for further statistical analysis. There was no significant difference between the baseline and postvaccination proteinuria (0.59 [interquartile range, 0.30–0.98] vs. 0.54 [0.33–0.92] g/d; P = 0.52) and hematuria (25.1 [8.9–72.2] vs. 25.4 [9–59.2]/μl; P = 0.47). Estimated glomerular filtration had a mild but statistically significant difference (68.39 [23.18] vs. 67.33 [23.53] ml/min per 1.73 m2; P = 0.03) from prevaccination to postvaccination (Table 2).

Table 2

Baseline and postvaccination characteristics of included patients

Characteristics	Baseline (n = 202)	Postvaccination (n = 202)	P value
Age, yr, mean (SD)	41.5 (11.3)	—	—
Sex
Male	107 (53.0)	—	—
Female	95 (47.0)	—	—
Disease
IgA nephropathy	197 (97.5)	—	—
IgA vasculitis nephritis	5 (2.5)	—	—
Vaccine
Inactivated vaccine	192 (95.0)	—	—
Recombinant subunit vaccine	10 (5.0)	—	—
eGFR, ml/min per 1.73 m2, mean (SD)	68.39 (23.18)	67.33 (23.53)	0.03a
Hematuria, /μl, median (IQR)	25.1 (8.9–72.2)	25.4 (9–59.2)	0.52b
Proteinuria, g/d, median (IQR)	0.59 (0.30–0.98)	0.54 (0.33–0.92)	0.47b
IS use during vaccination	31 (15.3)	—	—

eGFR, estimated glomerular filtration rate; IQR, interquartile range; IS, immunosuppressants.

Values are presented as n (%), unless otherwise indicated.

t test.

Wilcoxon signed-rank test.

Overall, the absolute incidence of adverse events was low, and COVID-19 vaccine was well tolerated in patients with IgAN, especially to those having relatively stable disease. Although glomerular filtration rate decline was observed in a few patients, the change was temporary. But close monitoring of the kidney function after vaccination should be offered to intervene as early as possible.