Medical Advisor Public Health Agency of Canada Ottawa, Canada
Background: The Safety Platform for Emergency vACcines (SPEAC) listed acute kidney injury (AKI) on its priority list of COVID-19 adverse events of special interest (AESI); however, a Brighton Collaboration case definition (BCCD) has not been planned for development due to resource limitations, weak evidence to justify inclusion on the AESI list, and the availability of the Kidney Disease Improving Global Outcomes (KDIGO) expert consensus group definition (which was recommended for use). Staging severity of disease, KDIGO’s definition is mainly relevant to hospital-acquired AKI and does not address levels of certainty of the diagnosis, among other limitations in vaccine safety surveillance settings.
Objectives: To describe a working definition for AKI used by the Public Health Agency of Canada that accounts for levels of certainty, in the context of limited clinical information available within adverse event following immunization (AEFI) reports in Canada. In addition, an approach to the classification of any renal or renal-related diagnosis occurring after immunization is outlined, to enable high quality safety signal detection and investigation.
Methods: Physicians working in vaccine safety engaged in a quality improvement exercise where they conducted a literature review, applied working knowledge, and consulted with a nephrologist to identify limitations of current approaches in addressing vaccine safety surveillance needs regarding renal AEFIs, and create processes and tools to mitigate these limitations.
Results: An AKI definition was developed, where any stage of the KDIGO definition would be classified as a definitive case (level of certainty 1). Criteria for probable (level 2) and possible (level 3) cases were proposed based on serum creatinine in the absence of baseline levels and non-objectively measured urine output. A case finding definition was developed for hematuria and/or proteinuria with hypertension, edema, and systemic symptoms (e.g., fever, fatigue, night sweats, shortness of breath, and headache), or acute interstitial nephritis, or glomerulonephritis. A standard operating procedure was developed to guide medical case reviews of renal AEFIs conducted by vaccine safety physicians.
Conclusions: KDIGO’s AKI definition has limited ability to support vaccine safety signal detection of renal AEFIs after COVID-19 immunization of interest, particularly when baseline creatinine levels are often unavailable or reported. An AKI definition incorporating levels of certainty can enhance the quality of vaccine safety surveillance investigations and consistency in the interpretation of often limited clinical information contained within AEFI reports.
