Schaalan Mona, Mohamed Waleed
Misr International University, Faculty of Pharmacy, Department of Biochemistry, Cairo, Egypt.
Cairo General Hospital, Chemistry Department, Cairo, Egypt.
Eur Cytokine Netw. 2017 Jun 1;28(2):52-62. doi: 10.1684/ecn.2017.0393.
Though significant progress has been made towards new diagnostic approaches for early detection of acute kidney injury (AKI) induced by different factors, there is still an urgent demand for a more specific and predictive biomarker for each type. The aim of this study is to unravel the potential diagnostic utility of circulating osteoprotegerin (OPG) in septic patients who developed AKI in the ICU, compared to cystatin C (a renal function maker) and KIM-1 (a kidney damage marker). Eighty patients (male = 43, female = 37) with ages ranging from 42 to 46 years and with sepsis, 40 of whom developed AKI, and 30 healthy controls were enrolled in this prospective study. Results revealed significant progressive elevation of OPG, along with cystatin C and KIM-1, among sepsis, severe sepsis, and sepsis-AKI patients. The progression of OPG levels paralleled the deterioration of kidney and endothelial functions from sepsis to sepsis-AKI, revealed as progressively increased levels of serum E-selectin (15.3%), endothelin-1 (ET-1) (19.6%), and decreased nitric oxide (NO) (29.7%), associated with elevations of TNF-α (25.5%) and TGF-β (18%). Their comparative prognostic validity of sepsis-AKI was assessed using ROC analysis, which revealed that OPG, KIM-1, and cystatin C showed similar AUCs (0.827-0.83) but with different sensitivities, viz., 84%, 88%, and 92%, respectively. Although cystatin showed 82% specificity, OPG showed a higher, similar specificity to KIM-1 of 85%, indicating its potential function as a marker of renal damage such as KIM-1. This study revealed a significant elevation of circulating OPG in septic patients with different levels of severity and those who progressed to AKI. Moreover, OPG showed a significant correlation to KIM-1 and cystatin, as well as conventional renal, inflammatory, and endothelial markers. Having a similar specificity to KIM-1, as evidenced by the ROC analysis, OPG has the potential to serve as a reliable biomarker of kidney damage in cases of sepsis-AKI.
尽管在针对不同因素所致急性肾损伤（AKI）的早期检测的新诊断方法方面已取得显著进展，但对于每种类型仍迫切需要一种更具特异性和预测性的生物标志物。本研究的目的是，与胱抑素C（一种肾功能标志物）和KIM-1（一种肾损伤标志物）相比，揭示循环骨保护素（OPG）在重症监护病房发生AKI的脓毒症患者中的潜在诊断效用。80例年龄在42至46岁之间的脓毒症患者（男性43例，女性37例）被纳入这项前瞻性研究，其中40例发生了AKI，并纳入了30名健康对照者。结果显示，在脓毒症、严重脓毒症和脓毒症相关性AKI患者中，OPG以及胱抑素C和KIM-1均有显著的进行性升高。OPG水平的变化与从脓毒症到脓毒症相关性AKI的肾脏和内皮功能恶化平行，表现为血清E-选择素水平逐渐升高（15.3%）、内皮素-1（ET-1）水平逐渐升高（19.6%）、一氧化氮（NO）水平降低（29.7%），同时伴有肿瘤坏死因子-α（TNF-α）升高（25.5%）和转化生长因子-β（TGF-β）升高（18%）。使用ROC分析评估了它们对脓毒症相关性AKI的比较预后有效性，结果显示OPG、KIM-1和胱抑素C的曲线下面积（AUC）相似（0.827 - 0.83），但敏感性不同，分别为84%、88%和92%。尽管胱抑素的特异性为82%，但OPG显示出更高的特异性，与KIM-1相似，为85%，表明其具有作为如KIM-1一样的肾损伤标志物的潜在功能。本研究显示，在不同严重程度的脓毒症患者以及进展为AKI的患者中，循环OPG显著升高。此外，OPG与KIM-1、胱抑素以及传统的肾脏、炎症和内皮标志物均显示出显著相关性。ROC分析表明，OPG与KIM-1具有相似的特异性，在脓毒症相关性AKI病例中，OPG有潜力作为可靠的肾损伤生物标志物。
