Therapeutic implications and pathophysiological role of calprotectin in acute kidney injury

钙卫蛋白在急性肾损伤中的治疗意义和病理生理学作用

• 批准号: 192650496
• 负责人: Professor Dr. Kai Schmidt-Ott
• 金额: --
• 依托单位: Medizinische Klinik I - Allgemeine Innere, Nephrologie, Gastroenterologie, Pneumologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/192650496?language=en
• 关键词: Therapeutic; implications; pathophysiological; role; calprotectin

Acute kidney injury (AKI) is classified according to its origin. There are hemodynamic (prerenal) and non-hemodynamic causes (intrarenal, postrenal). The prognosis of AKI crucially depends on an early diagnosis and immediate onset of therapy. The differential diagnosis of hemodynamic and intrarenal AKI, however, may be difficult. Unfortunately, there is no reliable marker for the non-invasive differentiation of these two entities. The present project investigates the use of urinary calprotectin as a new biomarker for the differentiation of hemodynamic and non-hemodynamic AKI. Calprotectin is a calcium-binding protein that is derived predominantly from neutrophils and monocytes. Being part oft the innate immune system, it is released as a ”damage-associated molecular pattern protein (DAMP)“ in a variety of inflammatory processes. In gastroenterology, fecal calprotectin concentration is a well established marker for the differentiation of inflammatory bowel disease and irritable bowel syndrome. Preliminary results of our group indicate that urinary calprotectin concentrations in patients with hemodynamic AKI is almost identical to healthy controls, whereas urinary calprotectin concentrations are approximately 1000 times higher in intrarenal AKI. If the preliminary results of our pilot study are confirmed by the current project, these findings will be of outstanding clinical relevance: A differentiation between hemodynamic and non-hemodynamic AKI would be available within minutes. “Calprotectin-negative” patients with hemodynamic AKI will immediately receive fluid repletion, whereas “calprotectin-positive” patients with intrarenal failure may require renal biopsy and specific treatment.

急性肾损伤 (AKI) 根据其来源进行分类，有血流动力学原因（肾前性）和非血流动力学原因（肾内性、肾后性）。AKI 的预后主要取决于早期诊断和立即开始治疗。然而，不幸的是，血流动力学和肾内 AKI 可能很困难，没有可靠的标记来非侵入性区分这两种实体，本项目研究了尿钙卫蛋白的用途。一种用于区分血流动力学和非血流动力学 AKI 的新生物标志物，钙卫蛋白是一种钙结合蛋白，主要源自中性粒细胞和单核细胞，是先天免疫系统的一部分，以“损伤相关分子模式蛋白”的形式释放。 （DAMP）“在胃肠病学中，粪便钙卫蛋白浓度是区分炎症性肠病和肠易激综合征的公认标志物。我们小组的结果表明，血流动力学 AKI 患者的尿钙卫蛋白浓度与健康对照者几乎相同，而肾内 AKI 患者的尿钙卫蛋白浓度大约高 1000 倍。研究结果具有显着的临床意义：血流动力学 AKI 和非血流动力学 AKI 之间的区别将在几分钟内实现，患有血流动力学 AKI 的“钙卫蛋白阴性”患者将立即接受液体治疗。肾功能衰竭的“钙卫蛋白阳性”患者可能需要肾活检和特殊治疗。

项目成果

Urinary biomarkers for the differentiation of prerenal and intrinsic pediatric acute kidney injury

区分肾前性和内源性小儿急性肾损伤的尿液生物标志物

• DOI: 10.1007/s00467-016-3418-1
• 发表时间: 2016
• 期刊: Pediatric Nephrology
• 影响因子: 3
• 作者: Westhoff JH;Fichtner A;Waldherr S;Pagonas N;Seibert FS;Babel N;Tönshoff B;Bauer F;Westhoff TH
• 通讯作者: Westhoff TH

Dynamics of Urinary Calprotectin after Renal Ischaemia

• DOI: 10.1371/journal.pone.0146395
• 发表时间: 2016-01-08
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Ebbing, Jan;Seibert, Felix S.;Westhoff, Timm H.
• 通讯作者: Westhoff, Timm H.

Urinary calprotectin: a new diagnostic marker in urothelial carcinoma of the bladder

• DOI: 10.1007/s00345-013-1227-8
• 发表时间: 2014-12-01
• 期刊: WORLD JOURNAL OF UROLOGY
• 影响因子: 3.4
• 作者: Ebbing, Jan;Mathia, Susanne;Westhoff, Timm H.
• 通讯作者: Westhoff, Timm H.

Urinary calprotectin, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin for the prediction of adverse outcome in pediatric acute kidney injury

• DOI: 10.1007/s00431-017-2907-y
• 发表时间: 2017-06-01
• 期刊: EUROPEAN JOURNAL OF PEDIATRICS
• 影响因子: 3.6
• 作者: Westhoff, Jens H.;Seibert, Felix S.;Westhoff, Timm H.
• 通讯作者: Westhoff, Timm H.

Urinary Calprotectin Differentiates Between Prerenal and Intrinsic Acute Renal Allograft Failure

尿钙卫蛋白可区分肾前性和内源性急性同种异体肾移植衰竭

• DOI: 10.1097/tp.0000000000001124
• 发表时间: 2017
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Seibert FS;Rosenberger C;Mathia S;Arns W;Andrea H;Pagonas N;Bauer F;Zidek W;Westhoff TH
• 通讯作者: Westhoff TH