预示危重病人长期肾脏损伤及死亡风险的生物标志物

  近日，来自匹兹堡大学的研究人员发现，危重疾病早期两种尿液生物标志物的较高水平和急性肾损伤(AKI)病人的长期预后不良结果直接相关，相关研究刊登于国际杂志Journal of the American Society of Nephrology上。AKI是一种经常影响重症监护病人的疾病，而且其往往在严重感染及术后会持续病症数小时至数天。

  文章中，研究者表示，组织抑制剂金属蛋白酶-2（TIMP-2）和IGF结合蛋白-7（IGFBP7）的结合或可帮助鉴别那些死亡风险较高及需要肾脏替代治疗的AKI病人；这两种生物标志物是揭示细胞压力、损伤及AKI发生的良好指示器。

  AKI在患者机体中发生往往并无症状，而且不会表现出一些警报信号，比如疼痛、呼吸短促或其它临床症状，尤其是在疾病发生早期，而那时进行临床干预往往可以有效预防患者AKI的发生。AKI在危重病人中的发生率较高，在患病期间某种程度的AKI甚至发生率可以达到50%，这往往会增加个体因肾脏衰竭死亡的风险。

  研究者John Kellum说道，我们发现，不仅上述生物标志物可以帮助预测AKI的发生，而且当这些生物标志物处于较高水平时，其会告知我们患者长期的预后结果；TIMP-2和IGFBP7或可以最大程度帮助临床医生和研究人员考虑应用于治疗其它常见的并发症。

  这项研究中，研究人员在北美及欧洲的35个医疗中心招募了692名危重病人，最初研究人员利用FDA批准的生物标志物检测手段NEPHROCHECK对进入重症监护病房的病人的预后进行了分析，研究人员发现，两种生物标志物TIMP-2和IGFBP7的结合同肾脏替代疗法或死亡的风险之间存在强相关关联。（转化医学网360zhyx.com）

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转化医学网推荐的原文摘要：

Classifying AKI by Urine Output versus Serum Creatinine Level
Journal of the American Society of Nephrology DOI:10.1681/ASN.2014070724
John A. Kellum*†, Florentina E. Sileanu*†‡, Raghavan Murugan*†, Nicole Lucko*†, Andrew D. Shaw*§ and Gilles Clermont*†
Severity of AKI is determined by the magnitude of increase in serum creatinine level or decrease in urine output. However, patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease. Thus, we investigated the relationship of AKI severity and duration across creatinine and urine output domains with the risk for RRT and likelihood of renal recovery and survival using a large, academic medical center database of critically ill patients. We analyzed electronic records from 32,045 patients treated between 2000 and 2008, of which 23,866 (74.5%) developed AKI. We classified patients by levels of serum creatinine and/or urine output according to Kidney Disease Improving Global Outcomes staging criteria for AKI. In-hospital mortality and RRT rates increased from 4.3% and 0%, respectively, for no AKI to 51.1% and 55.3%, respectively, when serum creatinine level and urine output both indicated stage 3 AKI. Both short- and long-term outcomes were worse when patients had any stage of AKI defined by both criteria. Duration of AKI was also a significant predictor of long-term outcomes irrespective of severity. We conclude that short- and long-term risk of death or RRT is greatest when patients meet both the serum creatinine level and urine output criteria for AKI and when these abnormalities persist.