Beunders Remi, Struck Joachim, Wu Alan H B, Zarbock Alexander, Di Somma Salvatore, Mehta Ravindra L, Koyner Jay L, Nadim Mitra K, Maisel Alan S, Murray Patrick T, Neath Sean-Xavier, Jaffe Allan, Pickkers Peter
Department of Intensive Care, Radboud University Medical Centre, Nijmegen, the Netherlands.
Sphingotec GmbH, Hennigsdorf, Germany.
J Appl Lab Med. 2017 Nov 1;2(3):400-412. doi: 10.1373/jalm.2017.023598.
The assessment of kidney function and detection of acute kidney injury (AKI) remain cumbersome. On the one hand, because of limited accuracy of established tests: The most widely used methods are creatinine based, which lack in sensitivity, as creatinine is not purely filtrated by the kidney and rises relatively late after onset of AKI. On the other hand, because of labor-intensiveness: Gold standard inulin clearance and comparable methods involve intravenous compound infusion, blood sampling at several time points, and have error-sensitive determination methods. In recent years, several biomarkers have been put forward (e.g., NGAL, KIM-1, TIMP-2*IGFBP-7), but clinical implementation is limited up to now.
Proenkephalin (PENK) represents a new candidate to determine kidney function. This peptide is cleaved from the precursor peptide preproenkephalin A alongside enkephalins (endogenous opioids) and is filtrated in the glomerulus. PENK plasma concentration appears to accurately represent glomerular filtration rate in patients diagnosed with sepsis or cardiac diseases. Moreover, increased PENK concentration is found to be associated with longer-term outcome concerning AKI and cardiac diseases. Lastly, the predominant receptor of enkephalins, the δ-opioid receptor, is expressed with the highest density in the kidney, suggesting that enkephalins could also exert a direct effect on kidney function.
In this review, we present an overview of enkephalins and the assessment of kidney function using this possible new functional biomarker PENK and compare it with established and novel biomarkers.
肾功能评估及急性肾损伤（AKI）的检测仍然繁琐。一方面，由于现有检测方法准确性有限：目前最广泛使用的方法基于肌酐，缺乏敏感性，因为肌酐并非完全由肾脏滤过，且在AKI发病后相对较晚才升高。另一方面，由于劳动强度大：金标准菊粉清除率及类似方法涉及静脉输注化合物、在多个时间点采血，且测定方法对误差敏感。近年来，已提出几种生物标志物（如中性粒细胞明胶酶相关脂质运载蛋白、肾损伤分子-1、金属蛋白酶组织抑制因子-2*胰岛素样生长因子结合蛋白-7），但目前临床应用有限。
前脑啡肽原（PENK）是一种用于评估肾功能的新候选物。该肽与脑啡肽（内源性阿片类物质）一同从前体肽前脑啡肽原A裂解而来，并在肾小球中滤过。在诊断为脓毒症或心脏病的患者中，PENK血浆浓度似乎能准确反映肾小球滤过率。此外，发现PENK浓度升高与AKI和心脏病的长期预后相关。最后，脑啡肽的主要受体δ-阿片受体在肾脏中表达密度最高，这表明脑啡肽也可能对肾功能产生直接影响。
在本综述中，我们概述了脑啡肽以及使用这种可能的新功能生物标志物PENK评估肾功能的情况，并将其与已有的和新的生物标志物进行比较。
