Hooper Levi, Heung Michael, Kenes Michael, Stringer Kathleen A, Mueller Bruce A, Pai Manjunath P
Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan.
Clin J Am Soc Nephrol. 2025 Apr 1;20(4):477-484. doi: 10.2215/CJN.0000000654. Epub 2025 Jan 31.
Modeling shows that serum cystatin C can detect AKI 6–48 hours earlier than serum creatinine, regardless of baseline kidney function. Absolute value diagnostic cutoffs are more effective than percentage-based thresholds for AKI detection across different CKD stages.
AKI is a common condition affecting a significant portion of hospitalized and critically ill patients. Current AKI diagnosis relies on serum creatinine (sCr), which has several recognized limitations that affect the timely detection and response to AKI management. Serum cystatin C (sCys) has characteristics that can overcome the limitations of sCr, but head-to-head comparisons of these biomarkers are difficult to study prospectively. A quantitative assessment of the kinetics of sCys and sCr during AKI is necessary to support clinical workflow implementation for AKI diagnosis and management.
A quantitative systems pharmacology model was developed using Matrix Laboratories and Simbiology (The MathWorks, Natick, MA), to simulate the concentration–time profiles of sCr and sCys under varying degrees of AKI across a spectrum of baseline kidney function. The model incorporated parameters from existing literature and used a contemporary sCr and sCys GFR equation to assess the time to reach AKI diagnostic criteria for both biomarkers.
The model demonstrated that sCys achieves steady-state concentration and meets AKI diagnostic thresholds significantly faster than sCr, with an advantage of 6–48 hours, depending on CKD stage. sCys exhibited greater sensitivity in detecting GFR reductions, with the ability to detect AKI within 12–24 hours after AKI, compared with 12–72 hours for sCr. The study also identified that for sCys, absolute value diagnostic cutoffs are more effective than percentage-based thresholds and can provide consistent detection across different CKD stages.
sCys has superior kinetics for early AKI detection compared with sCr, making it a valuable addition to AKI diagnostic protocols, particularly in high-risk populations. Daily monitoring of sCys in patients at risk of AKI would facilitate more timely detection and potentially improve clinical outcomes. Future research should focus on validating sCys diagnostic criteria and integrating it with other biomarkers to enhance AKI management.
模型显示，无论基线肾功能如何，血清胱抑素C检测急性肾损伤（AKI）比血清肌酐早6 - 48小时。在不同慢性肾脏病（CKD）阶段，绝对值诊断临界值在检测AKI方面比基于百分比的阈值更有效。
AKI是一种常见病症，影响着很大一部分住院患者和危重症患者。目前AKI的诊断依赖血清肌酐（sCr），其存在一些公认的局限性，影响了对AKI的及时检测和处理。血清胱抑素C（sCys）具有能够克服sCr局限性的特性，但对这些生物标志物进行直接比较的前瞻性研究很困难。对AKI期间sCys和sCr的动力学进行定量评估，对于支持AKI诊断和管理的临床工作流程实施很有必要。
使用Matrix Laboratories和Simbiology（MathWorks公司，马萨诸塞州纳蒂克）开发了一个定量系统药理学模型，以模拟在不同程度AKI以及一系列基线肾功能情况下sCr和sCys的浓度 - 时间曲线。该模型纳入了现有文献中的参数，并使用当代的sCr和sCys估算肾小球滤过率（GFR）方程来评估两种生物标志物达到AKI诊断标准的时间。
该模型表明，sCys达到稳态浓度并达到AKI诊断阈值的速度明显快于sCr，根据CKD阶段不同，优势为6 - 48小时。sCys在检测GFR降低方面表现出更高的敏感性，并能够在AKI发生后12 - 24小时内检测到AKI，而sCr则需要12 - 72小时。该研究还发现，对于sCys，绝对值诊断临界值比基于百分比的阈值更有效，并且能够在不同CKD阶段提供一致的检测结果。
与sCr相比，sCys在早期检测AKI方面具有更好的动力学特性。这使其成为AKI诊断方案中的一个有价值的补充，特别是在高危人群中。对有AKI风险的患者每日监测sCys将有助于更及时地检测，并可能改善临床结局。未来的研究应侧重于验证sCys诊断标准，并将其与其他生物标志物整合以加强AKI管理。
