Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan.
Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan.
Int J Mol Sci. 2024 Feb 1;25(3):1755. doi: 10.3390/ijms25031755.
This article provides a thorough overview of the biomarkers, pathophysiology, and molecular pathways involved in the transition from acute kidney injury (AKI) and acute kidney disease (AKD) to chronic kidney disease (CKD). It categorizes the biomarkers of AKI into stress, damage, and functional markers, highlighting their importance in early detection, prognosis, and clinical applications. This review also highlights the links between renal injury and the pathophysiological mechanisms underlying AKI and AKD, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses. In addition, various molecules play pivotal roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system reactions, and the cellular senescence of renal cells. Key signaling pathways, such as Wnt/β-catenin, TGF-β/SMAD, and Hippo/YAP/TAZ, promote fibrosis and impact renal function. The renin-angiotensin-aldosterone system (RAAS) triggers a cascade leading to renal fibrosis, with aldosterone exacerbating the oxidative stress and cellular changes that promote fibrosis. The clinical evidence suggests that RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed to confirm their full impact.
本文全面概述了从急性肾损伤（AKI）和急性肾疾病（AKD）向慢性肾脏病（CKD）转变过程中涉及的生物标志物、病理生理学和分子途径。它将 AKI 的生物标志物分为应激、损伤和功能标志物，强调了它们在早期检测、预后和临床应用中的重要性。本综述还强调了肾脏损伤与 AKI 和 AKD 背后的病理生理机制之间的联系，包括肾脏低灌注、脓毒症、肾毒性和免疫反应。此外，各种分子在炎症和缺氧中发挥关键作用，引发适应性修复、线粒体功能障碍、免疫系统反应和肾脏细胞的衰老。关键信号通路，如 Wnt/β-catenin、TGF-β/SMAD 和 Hippo/YAP/TAZ，促进纤维化并影响肾功能。肾素-血管紧张素-醛固酮系统（RAAS）引发导致肾纤维化的级联反应，醛固酮加剧促进纤维化的氧化应激和细胞变化。临床证据表明，RAS 抑制剂可能有助于预防 CKD 进展，特别是在 AKI 后，但需要更多的大规模试验来确认其全部影响。
