Pediatric acute kidney injury and adverse health outcomes: using a foundational framework to evaluate a causal link

Acute kidney injury (AKI) is a major global health problem, expensive to manage, and its associations with negative pediatric health outcomes have been clearly demonstrated. One of the most fundamental questions to consider as we use previous epidemiological information to advance research and care paradigms is the strength of the causal link between pediatric AKI and health outcomes. In this review, we apply the foundational framework of the Bradford Hill criteria to evaluate the extent to which a causal link exists between AKI and the associated adverse outcomes in children. Available data in children support a causal link between AKI and short-term outcomes including mortality, length of stay, and ventilation time. Clarifying the causal nature of longer term associations requires further high-quality observational studies in children, careful consideration of what defines the most meaningful and measurable longer term outcomes after pediatric AKI, and integration of evolving biological data related to mechanisms of disease. Preventing or mitigating AKI should lead to improved outcomes. Demonstrating such reversibility will solidify confidence in the causal relationship, improve child health, and highlight an aspect which is highly relevant to clinicians, scientists, and policy makers.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information