Comparison of serum creatinine and serum cystatin C as biomarkers to detect sepsis-induced acute kidney injury and to predict mortality in CD-1 mice
Comparison of serum creatinine and serum cystatin C as biomarkers to detect sepsis-induced acute kidney injury and to predict mortality in CD-1 mice
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DOI：
10.1152/ajprenal.00025.2013
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发表时间：
2014-10-15
影响因子：
4.2
通讯作者：
Yuen, Peter S. T.
中科院分区：
文献类型：
--
作者：
Leelahavanichkul, Asada;Souza, Ana Carolina P.;Yuen, Peter S. T.
急性肾损伤（阿基）显著增加脓毒症死亡率，但基于血清肌酐（SCr）变化时，阿基诊断延迟，部分原因是肌酐产生减少。在实验性脓毒症期间，我们比较了CD-1小鼠盲肠结扎穿孔（CLP）诱导脓毒症之前或之后3-18 h的血清胱抑素C（sCysC）、SCr和血尿素氮（BUN）与菊粉肾小球滤过率（iGFR）。在脓毒症和双侧肾切除术（BiNx）模型中，sCysC比SCr增加更快，达到峰值水平更快。在脓毒症期间，sCysC是比SCr更好的iGFR替代物。将sCysC与SCr值组合成复合生物标志物改善了与iGFR的相关性，优于任何单独的生物标志物或任何其他组合。我们确定了肾脏对BiNx处理sCysC的贡献。BiNx/CLP后sCysC和SCr低于单独BiNx后，尽管炎症和非肾器官损伤生物标志物增加。脓毒症减少了肾切除小鼠的CysC产生，而不改变体重或CysC空间。脓毒症减少sCysC的生产和增加非肾清除，类似于脓毒症对SCr的影响。在脓毒症后6小时测量sCysC、SCr和BUN，以将阿基与死亡率联系起来。脓毒症后6 h sCysC、BUN或SCr值高于中位值的小鼠比低于中位值的小鼠早死亡，对应于该模型中阿基与脓毒症死亡率的显著相关性。sCysC在对处于早期死亡风险的小鼠进行分类方面与SCr表现相似。我们得出结论，sCysC检测阿基早期和更好地反映iGFR在CLP诱导的脓毒症。这项研究表明，肾脏生物标志物需要在特定情况下进行评估。
Acute kidney injury (AKI) dramatically increases sepsis mortality, but AKI diagnosis is delayed when based on serum creatinine (SCr) changes, due in part, to decreased creatinine production. During experimental sepsis, we compared serum cystatin C (sCysC), SCr, and blood urea nitrogen (BUN) to inulin glomerular filtration rate (iGFR) before or 3-18 h after cecal ligation and puncture (CLP)-induced sepsis in CD-1 mice. sCysC had a faster increase and reached peak levels more rapidly than SCr in both sepsis and bilateral nephrectomy (BiNx) models. sCysC was a better surrogate of iGFR than SCr during sepsis. Combining sCysC with SCr values into a composite biomarker improved correlation with iGFR better than any biomarker alone or any other combination. We determined the renal contribution to sCysC handling with BiNx. sCysC and SCr were lower post-BiNx/CLP than post-BiNx alone, despite increased inflammatory and nonrenal organ damage biomarkers. Sepsis decreased CysC production in nephrectomized mice without changing body weight or CysC space. Sepsis decreased sCysC production and increased nonrenal clearance, similar to effects of sepsis on SCr. sCysC, SCr, and BUN were measured 6 h postsepsis to link AKI with mortality. Mice with above-median sCysC, BUN, or SCr values 6 h postsepsis died earlier than mice with below-median values, corresponding to a substantial AKI association with sepsis mortality in this model. sCysC performs similarly to SCr in classifying mice at risk for early mortality. We conclude that sCysC detects AKI early and better reflects iGFR in CLP-induced sepsis. This study shows that renal biomarkers need to be evaluated in specific contexts.