Harnessing Molecular Markers in Sepsis-Associated Acute Kidney Injury

Sepsis-associated acute kidney injury (SA-AKI) presents formidable challenges in emergency medicine, demanding timely recognition and evidence-based management. Emerging evidence suggests that molecular markers offer promising pathways to address these challenges by facilitating earlier risk assessment alongside established criteria.

Emerging data on microvascular and endothelial dysfunction suggest potential for earlier detection; however, these markers remain investigational and are not part of routine diagnosis. Markers reflecting endothelial dysfunction illuminate biological processes that are fundamental in sepsis-related kidney injury, offering hypotheses that may refine future diagnostic approaches.

Disruption of molecular pathways not only alters kidney function but also impairs systemic recovery, impacting overall sepsis management. This shared pathway pivot highlights the interconnected nature of sepsis and kidney injury, where markers like neutrophil gelatinase-associated lipocalin (NGAL) and [TIMP-2]*[IGFBP7] play important roles—used as adjunctive risk tools in select settings—while AKI diagnosis in practice remains defined by creatinine and urine output criteria.

Current evidence indicates these biomarkers can inform risk-adapted supportive care—such as hemodynamic optimization, avoidance of nephrotoxins, and earlier nephrology involvement—while serial measurement has been explored primarily in research settings. For patients experiencing rapid AKI onset, they may help flag high-risk physiology, prompting closer monitoring and timely supportive interventions.

Managing AKI during sepsis remains critical, especially when traditional signs are delayed. In practice, these tools may function as adjuncts to standard sepsis and AKI care, potentially supporting earlier ICU triage or nephrology consultation in patients who screen as high risk. Their integration should proceed alongside established protocols, with ongoing evaluation of impact on process measures and outcomes.

For frontline teams, practical responses to elevated biomarker risk include earlier nephrology consultation, avoidance of nephrotoxins (when feasible), and closer hemodynamic monitoring. Important limitations remain: thresholds and timing vary by setting, and definitive biomarker-guided treatment strategies have yet to be established.

Operational considerations include where testing fits in emergency workflows (triage vs. early ICU), result turnaround times, and pathways for escalation when risk is elevated. Centers adopting biomarker testing should align protocols with established sepsis bundles and AKI care processes, and track process measures such as time to nephrology consult and avoidance of nephrotoxins.

Evidence gaps remain. Key questions include which patients benefit most from testing, how serial measurements should be timed, and whether biomarker-informed care improves patient-centered outcomes beyond existing risk scores.

Future directions will likely focus on integrating biomarker data with clinical predictors and electronic alerts to support timely, guideline-concordant actions without overuse. Until then, clinicians can use these tools judiciously to complement creatinine and urine output criteria, particularly in patients at high risk for SA-AKI.

Key takeaways

• SA-AKI is time-critical; biomarkers are promising adjuncts that complement established creatinine and urine output criteria rather than replace them.
• NGAM and [TIMP-2]*[IGFBP7] may support early risk stratification in select settings, helping identify patients who warrant closer monitoring and earlier specialty input.
• Implementation opportunities include triage and consult workflows, but biomarker-guided therapy remains investigational and an active area of research.