Is Sex by Age Interaction The Missing Factor in Acute Kidney Injury Epidemiology?

Background and hypothesis Acute kidney injury (AKI) is a multifactorial syndrome associated with increased morbidity and mortality during hospitalization and in the long-term follow-up. Emerging evidence suggests that biological sex and age may influence kidney damage and recovery; however, the specific role of these biological variables on AKI outcomes remains to be fully elucidated. This retrospective study aimed to explore the impact of sex and age on AKI epidemiology and outcomes in a large cohort of hospitalized adults. Methods We analyzed clinical and administrative data from 87,087 adult patients admitted to two Italian university hospitals between 2016 and 2019. Excluding patients with stage 5 chronic kidney disease, we assessed AKI based on KDIGO criteria using serum creatinine trends during hospitalization. Demographic characteristics, comorbidities, estimated glomerular filtration rate, hospital stay, and outcomes were evaluated, with a focus on sex-based comparisons. Results AKI occurred in 20.6% of patients, with a higher incidence in females (21.4%) than males (19.8%). Female patients were older and had lower eGFR at hospital admission, less incidence of diabetes and CKD, but a more frequent diagnosis of congestive heart failure. While stage 3 AKI was more common in males, undiagnosed AKI was more frequent in females with stage 1 AKI. Of note, age-stratified analysis revealed a dynamic sex-related risk: AKI incidence was higher in males in younger age groups, whereas females showed a progressively higher incidence in the oldest age quartiles. However, outcomes such as mortality, ICU admission, and length of hospital stay were worse in the older male AKI population. Conclusions AKI incidence and in-hospital outcomes differ between males and females in an age-dependent manner. These findings emphasize the relevance of considering sex-by-age interaction when investigating AKI epidemiology and outcomes.