Reduced Production of Creatinine Limits Its Use as Marker of Kidney Injury in Sepsis
Reduced Production of Creatinine Limits Its Use as Marker of Kidney Injury in Sepsis
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DOI：
10.1681/asn.2008060617
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发表时间：
2009-06-01
影响因子：
13.6
通讯作者：
Star, Robert A.
中科院分区：
文献类型：
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作者：
Doi, Kent;Yuen, Peter S. T.;Star, Robert A.
虽然急性肾损伤的诊断和分期使用血清肌酐，但急性肌酐的变化滞后于肾损伤和恢复。急性肾损伤伴脓毒症时死亡风险增加；因此，我们试图探索血清肌酐在这种情况下的局限性。在小鼠中，双侧切除肾的小鼠通过盲肠结扎和穿刺诱导脓毒症增加了非肾器官损伤标志物和血清tnf - α。然而，脓毒症动物的血清肌酐明显低于双侧肾切除术和假肠结扎穿刺的动物。在这些情况下，氯喹治疗降低了非肾器官损伤标志物，但矛盾的是增加了血清肌酐。脓毒症显著降低肾切除小鼠肌酐的产生，而体重、红细胞压积或细胞外液容量没有变化。总之，脓毒症降低了肌酐的产生，从而减弱了脓毒症后血清肌酐的升高，可能限制了急性肾损伤的早期发现。这可能部分解释了为什么血清肌酐水平的小幅绝对升高与较差的临床结果相关。这些数据支持需要新的生物标志物来提供更好的肾损伤测量，特别是败血症患者。
Although diagnosis and staging of acute kidney injury uses serum creatinine, acute changes in creatinine lag behind both renal injury and recovery. The risk for mortality increases when acute kidney injury accompanies sepsis; therefore, we sought to explore the limitations of serum creatinine in this setting. In mice, induction of sepsis by cecal ligation and puncture in bilaterally nephrectomized mice increased markers of nonrenal organ injury and serum TNF-alpha. Serum creatinine, however, was significantly lower in septic animals than in animals subjected to bilateral nephrectomy and sham cecal ligation and puncture. Under these conditions treatment with chloroquine decreased nonrenal organ injury markers but paradoxically increased serum creatinine. Sepsis dramatically decreased production of creatinine in nephrectomized mice, without changes in body weight, hematocrit, or extracellular fluid volume. In conclusion, sepsis reduces production of creatinine, which blunts the increase in serum creatinine after sepsis, potentially limiting the early detection of acute kidney injury. This may partially explain why small absolute increases in serum creatinine levels are associated with poor clinical outcomes. These data support the need for new biomarkers that provide better measures of renal injury, especially in patients with sepsis.