Phenotype-Specific Heterogeneity in Acute Kidney Injury, Dialysis, and Mortality Among Hospitalized Patients with...

Background: Hospitalized patients with chronic kidney disease (CKD) are at high risk for acute kidney injury (AKI), dialysis, and mortality, yet CKD is often treated as a clinically homogeneous condition. Whether distinct cardiometabolic comorbidity patterns define meaningful inpatient CKD subgroups with differential outcome risks remains unclear. Methods: We conducted a retrospective cross-sectional study of adult hospitalizations for CKD using the 2022 Healthcare Cost and Utilization Project National Inpatient Sample. Hospitalizations were classified into five mutually exclusive CKD phenotypes using a rule-based framework based on diabetes mellitus, heart failure, hypertension, and vascular disease: isolated, hypertensive/vascular, metabolic, cardiorenal, and multimorbid cardiometabolic. Outcomes included AKI, dialysis during hospitalization, and in-hospital mortality. Survey-weighted multivariable logistic regression models were used to estimate adjusted odds ratios (aORs). Sensitivity analyses excluded end-stage kidney disease and dialysis dependence and restricted this study to non-transfer hospitalizations. The effect modification by age was assessed for dialysis. Results: Among 1,062,813 CKD hospitalizations, the unadjusted outcome rates varied substantially across phenotypes. After adjustment, cardiorenal CKD was associated with higher odds of acute kidney injury (aOR 1.16, 95% CI 1.12-1.19) and in-hospital mortality (aOR 1.54, 95% CI 1.50-1.58), whereas multimorbid cardiometabolic CKD demonstrated the strongest association with dialysis during hospitalization (aOR 2.34, 95% CI 2.25-2.43). Hypertensive/vascular CKD was not associated with a difference in mortality risk, while metabolic CKD was associated with a lower adjusted mortality rate compared to isolated CKD. Integrated analyses revealed distinct phenotype-specific risk profiles rather than a single severity gradient. Our findings were robust across the sensitivity analyses, and age significantly modified phenotype-dialysis associations. Conclusions: Hospitalized CKD populations exhibit marked phenotype-specific heterogeneity in AKI, dialysis, and mortality risk. A simple, clinically interpretable phenotype framework identifies distinct inpatient failure patterns and may inform future studies evaluating phenotype-specific risk stratification and management strategies.