Distribution of Acute and Chronic Kidney Disease Across Clinical Phenotypes for Sepsis

BACKGROUND: Sepsis is the most common cause of acute kidney injury (AKI) in critically ill patients. Four phenotypes (alpha, beta , gamma , delta) for sepsis, which have different outcomes and responses to treatment, were described using routine clinical data in the electronic health record. RESEARCH QUESTION: Do the frequencies of AKI, acute kidney disease (AKD), chronic kidney disease (CKD), and AKI on CKD differ by sepsis phenotype? STUDY DESIGN AND METHODS: This was a secondary analysis of a randomized clinical trial of early resuscitation, including patients with septic shock at 31 sites. After excluding patients with end-stage kidney disease and missing data, we determined frequencies of the following clinical outcomes: AKI (defined fi ned within 24 h as Kidney Disease: Improving Global Outcomes stages 2 or 3 or stage 1 with tissue inhibitor of metalloproteinases-2 x insulin-like growth factor binding protein 7 value of > 2.0), CKD, and AKD (persistence of AKI at any stage on day 7 after enrollment) across four phenotypes. We performed multivariable logistic regression to assess the risk-adjusted association between development of AKI and AKD and phenotype. RESULTS: Among 1,090 eligible patients, 543 patients (50%) had AKI. Across phenotypes, the frequencies of AKI varied, being highest in the delta and beta phenotypes (78% and 71%, respectively) and the lowest in the alpha phenotype (26%; P < .001). AKD occurred most often in the delta phenotype (41%) and least often in the alpha phenotype (8%; P < .001). The highest frequencies of CKD and of AKI on CKD were found in the beta phenotype (53% and 38% respectively; P < .001 for both). In the multivariable logistic regression models (alpha phenotype as reference), delta phenotype showed the strongest association with AKI (OR, 12.33; 95% CI, 7.81-19.47; P < .001) and AKD (OR, 9.18; 95% CI, 5.44-15.51; P < .001). INTERPRETATION: The rates of AKI and AKD differed across clinical sepsis phenotypes and are more common among patients with phenotypes beta and delta. Phenotype beta showed a higher level of underlying CKD that predisposed patients to new AKI. The alpha and gamma phenotypes showed lower frequencies of AKI and less progression to AKD.