Habshi Tahib, Shelke Vishwadeep, Kale Ajinath, Anders Hans-Joachim, Gaikwad Anil Bhanudas
Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani, Rajasthan, India.
Division of Nephrology, Department of Internal Medicine IV, Hospital of the Ludwig Maximilians University Munich, Munich, Germany.
J Cell Physiol. 2023 Jan;238(1):82-93. doi: 10.1002/jcp.30918. Epub 2022 Nov 21.
Acute kidney injury (AKI) and chronic kidney disease (CKD) are global health concerns with increasing rates in morbidity and mortality. Transition from AKI-to-CKD is common and requires awareness in the management of AKI survivors. AKI-to-CKD transition is a main risk factor for the development of cardiovascular disease and progression to end-stage kidney disease. The mechanisms driving AKI-to-CKD transition are being explored to identify potential molecular and cellular targets for renoprotective drug interventions. Endoplasmic reticulum (ER) stress and autophagy are involved in the process of AKI-to-CKD transition. Excessive ER stress results in the persistent activation of unfolded protein response, which is an underneath cause of kidney cell death. Moreover, ER stress modulates autophagy and vice-versa. Autophagy is a degradation defensive mechanism protecting cells from malfunction. However, the underlying pathological mechanism involved in this interplay in the context of AKI-to-CKD transition is still unclear. In this review, we discuss the crosstalk between ER stress and autophagy in AKI, AKI-to-CKD transition, and CKD progression. In addition, we explore possible therapeutic targets that can regulate ER stress and autophagy to prevent AKI-to-CKD transition to improve the long-term prognosis of AKI survivors.
急性肾损伤（AKI）和慢性肾脏病（CKD）是全球性的健康问题，其发病率和死亡率不断上升。从AKI转变为CKD很常见，在AKI幸存者的管理中需要引起重视。AKI向CKD的转变是心血管疾病发生和进展至终末期肾病的主要危险因素。目前正在探索驱动AKI向CKD转变的机制，以确定肾脏保护药物干预的潜在分子和细胞靶点。内质网（ER）应激和自噬参与了AKI向CKD的转变过程。过度的ER应激会导致未折叠蛋白反应的持续激活，这是肾细胞死亡的一个潜在原因。此外，ER应激调节自噬，反之亦然。自噬是一种保护细胞免受功能障碍的降解防御机制。然而，在AKI向CKD转变的背景下，这种相互作用所涉及的潜在病理机制仍不清楚。在这篇综述中，我们讨论了ER应激与自噬在AKI、AKI向CKD的转变以及CKD进展中的相互作用。此外，我们还探讨了可能的治疗靶点，这些靶点可以调节ER应激和自噬，以防止AKI向CKD的转变，从而改善AKI幸存者的长期预后。
