Abstract
Acute kidney injury (AKI) is a heterogeneous syndrome in which conventional stratification based on serum creatinine and urine output may fail to capture the full spectrum of underlying metabolic disturbances. In a retrospective cohort study of hospitalized adults with AKI admitted to Hospital General de Mazatlán between January 2022 and July 2025, we sought to identify biochemical phenotypes associated with major adverse kidney events (MAKE). Demographic, clinical, and biochemical variables, including urea, creatinine, calcium, phosphorus, potassium, hemoglobin, albumin, and pH, were standardized using z-scores and clustered using k-means analysis. The primary outcome was MAKE, defined as in-hospital mortality or new requirement for kidney replacement therapy (KRT). Among 797 patients, three distinct biochemical phenotypes were identified: Phenotype 1, characterized by relatively preserved biochemical parameters; Phenotype 2, defined by anemia and hypocalcemia; and Phenotype 3, marked by severe metabolic derangements. Phenotype 3 exhibited the most severe kidney dysfunction and metabolic instability, including anemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acidosis, and was strongly associated with MAKE (odds ratio [OR] 3.39, 95% confidence interval [CI] 2.12-5.40; p < 0.001), in-hospital mortality (OR 2.47, 95% CI 1.48-4.12; p < 0.001), and initiation of KRT (OR 5.80, 95% CI 1.60-21.12; p = 0.007). Phenotype 2 was more frequently observed in women and was associated with AKI stage 3, gastrointestinal bleeding, and malignancy, but was not independently associated with MAKE. Biochemical phenotyping identified clinically meaningful AKI subgroups and highlighted a high-risk phenotype characterized by profound metabolic instability and adverse kidney outcomes.