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Background <p>Acute kidney injury (AKI) is a significant complication among critically ill patients, particularly those with sepsis, yet no specific therapies exist. Progress in some diseases has been achieved by analyzing individuals who appear resistant. This study sought to develop a framework to investigate AKI resistance using clinical phenotyping and biomarkers and applied this framework to a large cohort of patients with septic shock.</p> Methods <p>We performed a retrospective analysis of patients enrolled in the Protocolized Care for Early Septic Shock (ProCESS) trial. We measured urinary tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein 7 (IGFBP7), and kidney injury molecule 1 (KIM-1) 6&#xa0;h after the start of resuscitation. AKI was defined first as high risk by [TIMP-2]•[IGFBP7] &gt; 1.0 (ng/mL)²/1000 and either meeting Kidney Disease Improving Global Outcomes Criteria (KDIGO) criteria within 7 days after the start of resuscitation or having [KIM-1] &gt; 2.0 ng/ml. AKI resistance was defined as the combination of (a) high-risk by [TIMP-2]•[IGFBP7] &gt; 1.0 (ng/mL)²/1000 but without meeting (b) KDIGO AKI criteria nor (c) [KIM-1] &gt; 2.0 ng/ml. We compared clinical characteristics and outcomes across three groups: AKI-resistant, AKI, and reduced risk, which was defined as [TIMP-2]•[IGFBP7] &lt; 1.0 (ng/mL)²/1000.</p> Results <p>Among 573 patients, 339 (59.2%) had reduced risk, 194 (33.9%) developed AKI, and 40 (7%) were AKI-resistant. Median (IQR) non-renal SOFA scores were lower for patients at reduced risk for AKI (5 [2–7]) than for those with AKI resistance (6 [4.5-8], <i>P</i> &lt; 0.01) or AKI (6 [5–9], <i>P</i> &lt; 0.01). Baseline characteristics did not differ between AKI-resistant and AKI-affected individuals. However, AKI-resistant patients experienced significantly lower 30-day mortality (10% vs. 32%; adjusted OR 0.26, 95% CI: 0.09–0.80, <i>P</i> = 0.02) and shorter ICU stays when compared to those with AKI.</p> Conclusion <p>Despite greater illness severity, AKI-resistant patients had similar mortality and length of stay as lower-risk patients but better outcomes than those with AKI. Studying these patients may reveal novel therapeutic targets for AKI prevention and treatment.</p>

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Discovery of a resistant cohort to acute kidney injury: insights from patients with septic shock

  • 期刊论文

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  • 发表日期：

    2025年10月8日

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  • Dana Y. Fuhrman,
  • Towia A. Libermann,
  • Neil A. Hukriede,
  • Luca Molinari,
  • Samir M. Parikh,
  • John A. Kellum

摘要

Background

Acute kidney injury (AKI) is a significant complication among critically ill patients, particularly those with sepsis, yet no specific therapies exist. Progress in some diseases has been achieved by analyzing individuals who appear resistant. This study sought to develop a framework to investigate AKI resistance using clinical phenotyping and biomarkers and applied this framework to a large cohort of patients with septic shock.

Methods

We performed a retrospective analysis of patients enrolled in the Protocolized Care for Early Septic Shock (ProCESS) trial. We measured urinary tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein 7 (IGFBP7), and kidney injury molecule 1 (KIM-1) 6 h after the start of resuscitation. AKI was defined first as high risk by [TIMP-2]•[IGFBP7] > 1.0 (ng/mL)²/1000 and either meeting Kidney Disease Improving Global Outcomes Criteria (KDIGO) criteria within 7 days after the start of resuscitation or having [KIM-1] > 2.0 ng/ml. AKI resistance was defined as the combination of (a) high-risk by [TIMP-2]•[IGFBP7] > 1.0 (ng/mL)²/1000 but without meeting (b) KDIGO AKI criteria nor (c) [KIM-1] > 2.0 ng/ml. We compared clinical characteristics and outcomes across three groups: AKI-resistant, AKI, and reduced risk, which was defined as [TIMP-2]•[IGFBP7] < 1.0 (ng/mL)²/1000.

Results

Among 573 patients, 339 (59.2%) had reduced risk, 194 (33.9%) developed AKI, and 40 (7%) were AKI-resistant. Median (IQR) non-renal SOFA scores were lower for patients at reduced risk for AKI (5 [2–7]) than for those with AKI resistance (6 [4.5-8], P < 0.01) or AKI (6 [5–9], P < 0.01). Baseline characteristics did not differ between AKI-resistant and AKI-affected individuals. However, AKI-resistant patients experienced significantly lower 30-day mortality (10% vs. 32%; adjusted OR 0.26, 95% CI: 0.09–0.80, P = 0.02) and shorter ICU stays when compared to those with AKI.

Conclusion

Despite greater illness severity, AKI-resistant patients had similar mortality and length of stay as lower-risk patients but better outcomes than those with AKI. Studying these patients may reveal novel therapeutic targets for AKI prevention and treatment.