循环S100A12与脓毒症相关急性肾损伤的关联及临床定位

Circulating S100A12 in Sepsis-Associated Acute Kidney Injury: Association and Clinical Positioning

摘要: 脓毒症相关急性肾损伤(sepsis-associated acute kidney injury, SA-AKI)是危重患者常见的器官功能障碍之一，与死亡风险升高、肾脏替代治疗需求增加及远期肾脏不良结局相关。目前，急性肾损伤(acute kidney injury, AKI)的识别与分期仍主要依据改善全球肾脏病预后组织(Kidney Disease: Improving Global Outcomes, KDIGO)规定的血清肌酐变化及尿量减少标准，但这些指标对AKI发生前风险及全身炎症状态的反映有限。S100钙结合蛋白A12 (S100 calcium-binding protein A12, S100A12)主要由中性粒细胞等髓系细胞表达和释放，其循环水平与先天免疫激活及全身炎症状态相关。本文聚焦循环S100A12与SA-AKI的临床研究证据，结合其生物学基础评估现有证据的可靠性，并讨论临床应用仍需解决的关键问题。目前仅有两项临床研究直接评价循环S100A12与SA-AKI的关系，且结果不一致：一项研究未发现脓毒症患者AKI与非AKI亚组间血浆S100A12水平存在显著差异，另一项单中心前瞻性队列则显示循环S100A12与SA-AKI相关，并具有一定区分度。由于采样时序尚未充分明确、结局定义存在差异，且检测方法尚未标准化、缺乏独立外部验证，目前还不能确定S100A12能否在AKI发生前识别高风险患者，也不能证明其能在现有临床评估基础上提供额外价值。现阶段，循环S100A12更适合作为炎症相关候选辅助风险标志物，尚不能替代KDIGO标准或独立指导临床决策。

Abstract: Sepsis-Associated acute kidney injury (SA-AKI) is a common complication in critically ill patients and is associated with higher mortality, an increased requirement for kidney replacement therapy, and adverse long-term renal outcomes. Acute kidney injury (AKI) is currently identified and staged mainly using Kidney Disease: Improving Global Outcomes (KDIGO) criteria based on changes in serum creatinine and urine output; however, these indicators have limited ability to identify risk before AKI onset or reflect systemic inflammatory status. S100 calcium-binding protein A12 (S100A12) is predominantly expressed and released by myeloid cells such as neutrophils, and its circulating level is associated with innate immune activation and systemic inflammation. This review focuses on clinical evidence regarding circulating S100A12 in SA-AKI, evaluates the reliability of current evidence in light of its biological basis, and discusses key issues that must be resolved before clinical application. Only two clinical studies have directly evaluated the relationship between circulating S100A12 and SA-AKI, and their results were inconsistent: one found no significant difference in plasma S100A12 between patients with sepsis who had AKI and those who did not, whereas a single-center prospective cohort showed that circulating S100A12 was associated with SA-AKI and showed discriminatory ability. Because the temporal relationship between S100A12 sampling and AKI onset remains unclear, outcome definitions differ, assay methods have not been standardized, and independent external validation is lacking, it remains uncertain whether S100A12 can identify high-risk patients before AKI onset or provide additional value beyond current clinical assessment. At present, circulating S100A12 is better regarded as an inflammation-related candidate adjunctive marker for risk assessment and should not replace KDIGO criteria or independently guide clinical decisions.