THE IMPACT of sepsis on survival in critically ill patients with acute kidney injury (AKI) may depend strongly on how sick patients are at baseline, according to a large retrospective study.
Sepsis and AKI frequently co-occur in intensive care units (ICUs) and are each associated with high mortality. Sepsis is generally considered a negative prognostic factor in AKI, but researchers questioned whether this relationship is consistent across the full spectrum of illness severity.
To investigate, the team analysed data from 35,926 adults with AKI, examining whether baseline illness severity, measured using the Simplified Acute Physiology Score II (SAPS II), modified the association between sepsis and 30-day survival. Sepsis was defined according to Sepsis-3 criteria. Multivariable logistic regression models were adjusted for demographics, comorbidities and organ dysfunction.
Sepsis Impact on AKI Survival Varies by Illness Severity
The findings revealed a striking interaction between sepsis and illness severity (p<0.001). At lower levels of severity (SAPS II score of 20), sepsis was associated with a 4.3 percentage point reduction in 30-day survival, confirming its expected harmful effect in relatively less critically ill patients.
However, this association reversed at the highest levels of severity. Among patients with a SAPS II score of 90, sepsis was linked to a 23.6 percentage point increase in 30-day survival. Overall, this represented a net reversal of 27.9 percentage points across the severity spectrum. The pattern remained robust in multiple sensitivity analyses.
High Illness Severity Linked to Paradoxical Sepsis Survival Benefit
The authors describe this as a paradoxical finding that challenges the assumption that sepsis uniformly worsens outcomes in AKI. In the sickest patients, they suggest, sepsis may signal a form of organ dysfunction that is potentially reversible, rather than irreversible systemic collapse.
The results highlight the importance of incorporating baseline illness severity into prognostic assessments for AKI. Relying on severity scores alone may underestimate recovery potential in patients with severe septic AKI.
While the study was observational and cannot establish causality, it underscores the complexity of critical illness and suggests that risk stratification tools in the ICU may need refinement to better account for interactions between syndromes such as sepsis and AKI.
Reference
Derakhshan M et al. Illness severity modifies the association between sepsis and survival in critically ill patients with acute kidney injury. Clin Exp Nephrol. 2026.doi: 10.1007/s10157-026-02824-x.
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