Internal Medicine Department, Hospital of Marcianise, ASL Caserta, 81031 Caserta, Italy.
Emergency Department, Hospital of Latina, ASL Latina, 04100 Latina, Italy.
Cells. 2022 Nov 29;11(23):3820. doi: 10.3390/cells11233820.
Acute kidney injury (AKI) is a major clinical problem associated with increased morbidity and mortality. Despite intensive research, the clinical outcome remains poor, and apart from supportive therapy, no other specific therapy exists. Furthermore, acute kidney injury increases the risk of developing chronic kidney disease (CKD) and end-stage renal disease. Acute tubular injury accounts for the most common intrinsic cause of AKI. The main site of injury is the proximal tubule due to its high workload and energy demand. Upon injury, an intratubular subpopulation of proximal epithelial cells proliferates and restores the tubular integrity. Nevertheless, despite its strong regenerative capacity, the kidney does not always achieve its former integrity and function and incomplete recovery leads to persistent and progressive CKD. Clinical and experimental data demonstrate sexual differences in renal anatomy, physiology, and susceptibility to renal diseases including but not limited to ischemia-reperfusion injury. Some data suggest the protective role of female sex hormones, whereas others highlight the detrimental effect of male hormones in renal ischemia-reperfusion injury. Although the important role of sex hormones is evident, the exact underlying mechanisms remain to be elucidated. This review focuses on collecting the current knowledge about sexual dimorphism in renal injury and opportunities for therapeutic manipulation, with a focus on resident renal progenitor stem cells as potential novel therapeutic strategies.
急性肾损伤 (AKI) 是一种与发病率和死亡率增加相关的主要临床问题。尽管进行了深入研究，但临床结果仍然不佳，除了支持性治疗外，尚无其他特定治疗方法。此外，急性肾损伤会增加慢性肾脏病 (CKD) 和终末期肾病的风险。急性肾小管损伤是 AKI 的最常见内在原因。损伤的主要部位是近端肾小管，因为它的工作量和能量需求很高。在损伤后，近端上皮细胞的一个肾小管亚群增殖并恢复肾小管完整性。然而，尽管肾脏具有很强的再生能力，但它并不总是能恢复到以前的完整性和功能，不完全恢复会导致持续和进行性的 CKD。临床和实验数据表明，肾脏解剖结构、生理学和对肾脏疾病的易感性存在性别差异，包括但不限于缺血再灌注损伤。一些数据表明女性性激素具有保护作用，而另一些数据则强调男性激素在肾缺血再灌注损伤中的有害作用。尽管性激素的重要作用是显而易见的，但确切的潜在机制仍有待阐明。本综述重点收集了关于肾损伤中性别二态性的现有知识和治疗干预的机会，重点关注肾固有祖细胞作为潜在的新型治疗策略。
