Pejchinovski Ilinka, Turkkan Sibel, Pejchinovski Martin
Department of Quality Assurance, Nikkiso Europe GmbH, 30885 Langenhagen, Germany.
Department of Analytical Instruments Group, Thermo Fisher Scientific, 82110 Germering, Germany.
Diagnostics (Basel). 2023 Aug 11;13(16):2648. doi: 10.3390/diagnostics13162648.
Acute Kidney Injury (AKI) is currently recognized as a life-threatening disease, leading to an exponential increase in morbidity and mortality worldwide. At present, AKI is characterized by a significant increase in serum creatinine (SCr) levels, typically followed by a sudden drop in glomerulus filtration rate (GFR). Changes in urine output are usually associated with the renal inability to excrete urea and other nitrogenous waste products, causing extracellular volume and electrolyte imbalances. Several molecular mechanisms were proposed to be affiliated with AKI development and progression, ultimately involving renal epithelium tubular cell-cycle arrest, inflammation, mitochondrial dysfunction, the inability to recover and regenerate proximal tubules, and impaired endothelial function. Diagnosis and prognosis using state-of-the-art clinical markers are often late and provide poor outcomes at disease onset. Inappropriate clinical assessment is a strong disease contributor, actively driving progression towards end stage renal disease (ESRD). Proteins, as the main functional and structural unit of the cell, provide the opportunity to monitor the disease on a molecular level. Changes in the proteomic profiles are pivotal for the expression of molecular pathways and disease pathogenesis. Introduction of highly-sensitive and innovative technology enabled the discovery of novel biomarkers for improved risk stratification, better and more cost-effective medical care for the ill patients and advanced personalized medicine. In line with those strategies, this review provides and discusses the latest findings of proteomic-based biomarkers and their prospective clinical application for AKI management.
急性肾损伤(AKI)目前被认为是一种危及生命的疾病,导致全球发病率和死亡率呈指数级增长。目前,AKI的特征是血清肌酐(SCr)水平显著升高,通常随后肾小球滤过率(GFR)突然下降。尿量变化通常与肾脏无法排泄尿素和其他含氮废物有关,导致细胞外液量和电解质失衡。有人提出几种分子机制与AKI的发生和发展有关,最终涉及肾上皮肾小管细胞周期停滞、炎症、线粒体功能障碍、近端肾小管无法恢复和再生以及内皮功能受损。使用最先进的临床标志物进行诊断和预后评估往往较晚,且在疾病发作时预后不佳。不恰当的临床评估是疾病的一个重要促成因素,积极推动疾病进展至终末期肾病(ESRD)。蛋白质作为细胞的主要功能和结构单位,为在分子水平上监测疾病提供了机会。蛋白质组学图谱的变化对于分子途径的表达和疾病发病机制至关重要。高灵敏度和创新技术的引入使得能够发现新的生物标志物,以改善风险分层,为患病患者提供更好、更具成本效益的医疗护理,并推进个性化医疗。符合这些策略,本综述提供并讨论了基于蛋白质组学的生物标志物的最新发现及其在AKI管理中的前瞻性临床应用。