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Based on updated definitions, SA-AKI affects nearly half of all patients with sepsis in the ICU and one‑sixth of all ICU admissions, according to research.

Based on updated consensus definitions, sepsis-associated acute kidney injury (SA‑AKI) affects nearly half of all patients with sepsis in the ICU and one‑sixth of all ICU admissions, with substantial attributable harm, according to a recent study published in Critical Care.

“Applying updated consensus definitions highlights the high prevalence of SA-AKI in the ICU and its significant associated morbidity and mortality,” wrote study author Tomonori Takeuchi, MD, University of Alabama at Birmingham, and colleagues.

According to the authors, sepsis and acute kidney injury (AKI) are heterogeneous syndromes whose evolving definitions have complicated epidemiological assessments. SA‑AKI, now uniformly defined by the 28th Acute Disease Quality Initiative Workgroup as the concurrence of sepsis (per Sepsis‑3 criteria) and AKI (per Kidney Disease: Improving Global Outcomes criteria [KDIGO]) occurring within 7 days of sepsis diagnosis, carries a mortality and morbidity burden that exceeds non‑septic AKI and sepsis alone.

Methodology

The researchers conducted a retrospective analysis of 187,888 adult ICU admissions across two academic medical centers (University of Alabama at Birmingham: February 2010–June 2022; University of Kentucky: January 2009–March 2020). Patients were stratified into four groups: SA‑AKI, sepsis only, AKI only, and concurrent sepsis and AKI not meeting SA‑AKI criteria. Baseline demographics, comorbidities (Charlson Comorbidity Index), and illness severity (Sequential Organ Failure Assessment [SOFA]) were recorded. Sepsis onset was determined by culture and antibiotic timestamps and a SOFA increase greater than or equal to 2, while AKI onset classification followed KDIGO serum creatinine and urine‑output criteria. SA‑AKI cases were further subclassified as early (≤ 48 hours post‑sepsis) or late (2–7 days), with septic shock defined by vasopressor use plus lactate greater than or equal to 2.0 mmol/L. Clinical outcomes included in‑hospital mortality and major adverse kidney events (MAKE) at discharge.

Incidence & Phenotypes

The study showed that of all ICU admissions, 33.8% met Sepsis‑3 criteria; 46.6% of these developed SA‑AKI (15.8% overall), with a median onset 1 day post-sepsis. Early SA‑AKI accounted for approximately two‑thirds of cases; late onset represented 36.1%. Allowing AKI to precede sepsis onset by up to 2 days increased SA‑AKI prevalence by 7%, suggesting pre‑recognition injury in select patients, according to the authors.

Outcomes & Comparative Risk

Based on study findings, patients with SA‑AKI exhibited a 2‑fold higher hospital mortality (25.0% vs. 11.2%) and nearly 3‑fold higher MAKE incidence (37.7% vs 12.9%) than patients with sepsis‑only. In adjusted Cox models, SA‑AKI conferred a 59% higher mortality risk relative to sepsis alone (HR 1.59; 95% CI 1.51–1.66) and a 3.35‑fold increase in odds of MAKE. Early and late phenotypes exhibited similar mortality hazards, although late SA‑AKI was linked to greater MAKE rates at discharge. The presence of septic shock further doubled mortality and raised MAKE incidence to 50%.

Clinical Characteristics

The authors reported that patients with SA‑AKI were older, bore a greater comorbidity burden (including chronic kidney disease), and had lower baseline estimated glomerular filtration rate. Early SA‑AKI correlated with acute comorbidities (eg, diabetes, hypertension) and higher acuity (SOFA scores), whereas late SA‑AKI was more often associated with chronic conditions (eg, liver cirrhosis) and nephrotoxin exposure. Nearly one‑eighth of patients with SA‑AKI required kidney replacement therapy within the first week.

Implications & Future Directions

“Using contemporary definitions of SA-AKI, this study provides an update on the epidemiology of SA-AKI in critically ill adult patients as well as demonstrated the significant morbidity and mortality of SA-AKI in comparison to sepsis and AKI in isolation,” the authors concluded. “Updated epidemiology of a common condition, such as SA-AKI, is a critical first step towards identifying vulnerable populations, guiding quality assurance, and informing policy to promote health equity.”