Cardiorenal Metabolic Modifiers of In-Hospital Outcomes Among Hospitalizations with Acute Kidney Injury

Background: Acute kidney injury (AKI) is a common and high-risk complication of hospitalization that frequently occurs in patients with chronic cardiometabolic disease. Although heart failure (HF) and diabetes mellitus (DM) are prevalent among hospitalized adults and may differentially modify AKI-associated outcomes, their joint impact on in-hospital risk profiles and cumulative burden remains incompletely characterized. Methods: We conducted a retrospective analysis of adult hospitalizations complicated by AKI using a nationally representative inpatient database. Hospitalizations were classified into four cardiorenal metabolic phenotypes: AKI alone, AKI with HF, AKI with DM, and AKI with both HF and DM. Primary outcomes included in-hospital mortality, dialysis initiation, and mechanical ventilation. Survey-weighted multivariable logistic regression models incorporating HF, DM, and their interaction were used to estimate adjusted associations and model-based predicted probabilities. Adjusted risks were visualized across outcomes, and a composite burden metric was constructed to summarize cumulative in-hospital adverse events. Results: AKI outcomes varied substantially across cardiorenal metabolic phenotypes. HF was consistently associated with higher adjusted mortality and mechanical ventilation risk, whereas DM alone was associated with lower adjusted mortality. A significant interaction between HF and DM was observed regarding dialysis initiation, with a disproportionately higher adjusted risk when both conditions coexisted. Integrated visualization across outcomes demonstrated distinct risk profiles by phenotype, with the combined HF and DM group exhibiting the highest cumulative burden of adverse in-hospital events. Conclusions: Among hospitalizations complicated by AKI, the underlying cardiorenal metabolic status is associated with marked heterogeneity in in-hospital outcomes. HF appears to be a dominant modifier of AKI-associated risk, while DM exerts outcome-specific effects and synergistically increases the risk of dialysis initiation when combined with HF. These findings highlight the importance of incorporating cardiometabolic context into AKI risk stratification approaches and underscore the value of multidimensional in-hospital assessments.