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 (α, β, γ, δ) for sepsis, which have different outcomes and response to treatment, were described using routine clinical data in the electronic health record. Research questions 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 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 within 24h as KDIGO stage 2 or 3 or stage 1 with [TIMP-2]•[IGFBP7] >2.0), CKD, and AKD (persistence of AKI at any stage, on day 7 following enrollment) across four phenotypes. We performed multivariable logistic regression to assess the risk-adjusted association between development of AKI/AKD and phenotype. Results Among 1,090 eligible patients, 543 (50%) patients had AKI. Across phenotypes, the frequencies of AKI varied, being highest in the δ and β phenotypes (78% and 71%, respectively), and lowest in α (26%, P<0.001). AKD occurred most often in δ (41%) and least often in α (8% P<0.001). The highest frequencies of CKD and of AKI-on-CKD were found in β (53% and 38% respectively, both P<0.001). In the multivariable logistic regression models (α as reference), δ showed the strongest association with AKI (odds ratio (OR) 12.33, 95%CI 7.81-19.47, P<0.001) and AKD (OR 9.18, 95%CI 5.44-15.51, P<0.001). Interpretation The rates of AKI and AKD differed across clinical sepsis phenotypes and are more common among patients with phenotype β and δ. β-type had a higher level of underlying CKD that predisposed to new AKI. α and γ had lower frequencies of AKI and less progression to AKD.