Global burden of vaccine-associated kidney injury using an international pharmacovigilance database

Abstract

Global evidence on the association between vaccines and renal adverse events (AEs) is inconclusive. This pharmacovigilance study analyzed a total of 120,715,116 reports from VigiBase collected between 1967 and 2022. We evaluated the global reporting of acute kidney injury (AKI), glomerulonephritis (GN), and tubulointerstitial nephritis (TIN) and assessed disproportionate signals between vaccines and renal AEs using reporting odds ratios (ROR) and the lower limit of the 95% confidence interval of the information component (IC₀₂₅) in comparison with the entire database. The number and proportion of reports on AKI, GN, and TIN gradually increased, with a substantial increase after 2020. Disproportionate reporting of AKI was significant for COVID-19 mRNA vaccines (ROR, 2.38; IC₀₂₅, 1.09). Fourteen vaccines were significantly disproportionate for higher GN reporting, and the highest disproportionality for GN reporting was observed for COVID-19 mRNA (ROR, 13.41; IC₀₂₅, 2.90) and hepatitis B vaccines (ROR, 11.35; IC₀₂₅, 3.18). Disproportionate TIN reporting was significant for COVID-19 mRNA (ROR, 2.43; IC₀₂₅, 0.99) and human papillomavirus (ROR, 1.75; IC₀₂₅, 0.19) vaccines. Significant disproportionality in the reporting of AKI, GN, and TIN was observed in patients exposed to multiple vaccines, including COVID-19 mRNA vaccines, alongside increasing global reports of vaccine-associated renal AEs.

Keywords: Acute kidney injury; Glomerulonephritis; Pharmacovigilance; Tubulointerstitial nephritis; Vaccines.

Fig. 1

Temporal changes in the reported counts of vaccine- and drug-associated renal adverse events, and a world map showing reported cases across continents. The reported counts of AKI (A), GN (B), and TIN (C) are presented over timeframe. The number of each renal AE for vaccines (red bars) and all drugs (blue bars) is listed, and the proportions of renal AEs among all drug-related AEs are displayed as percentages adjacent to the red bars. Globally reported counts of AKI (D), GN (E), and TIN (F) are shown across continents. Regions with higher counts are indicated in red, while those with lower counts are marked in blue. AKI, acute kidney injury; GN, glomerulonephritis; TIN, tubulointerstitial nephritis.

Fig. 2

Cumulative counts of AKI (A), GN (B), and TIN (C) reports per year in association with different vaccines. Other vaccines included brucellosis, plague, typhus, leptospirosis, rabies, yellow fever, smallpox, Ebola, and dengue vaccines. The COVID-19 vaccine is illustrated separately within the same row because of its distinct temporal distribution. Ad5, adenovirus type-5; DTaP-IPV-Hib, diphtheria, tetanus, pertussis, polio, and Hemophilus influenzae type b; HPV, human papillomavirus; MMR, measles, mumps, and rubella. AKI, acute kidney injury; GN, glomerulonephritis; TIN, tubulointerstitial nephritis

Fig. 3

The overlap between vaccine-associated AKI, GN, and TIN. A total of 228 cases overlapped between AKI and GN, 82 cases between AKI and TIN, and 35 cases between GN and TIN. In addition, 24 cases were reported to overlap across all three renal AEs. AKI, acute kidney injury; GN, glomerulonephritis; TIN, tubulointerstitial nephritis.