Podocyte injury is a major cause of proteinuria in kidney diseases, and persistent loss of podocytes leads to rapid irreversible progression of kidney disease. Sirtuins, a class of nicotinamide adenine dinucleotide-dependent deacetylases, can promote DNA repair, modify transcription factors, and regulate the cell cycle. Additionally, sirtuins play a critical role in renoprotection, particularly against podocyte injury. They also have pleiotropic protective effects on podocyte injury-related glomerular diseases, such as improving the immune inflammatory status and oxidative stress levels, maintaining mitochondrial homeostasis, enhancing autophagy, and regulating lipid metabolism. Sirtuins deficiency causes podocyte injury in different glomerular diseases. Studies using podocyte sirtuin-specific knockout and transgenic models corroborate this conclusion. Of note, sirtuin activators have protective effects in different podocyte injury-related glomerular diseases, including diabetic kidney disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, and lupus nephritis. These findings suggest that sirtuins are promising therapeutic targets for preventing podocyte injury. This review provides an overview of recent advances in the role of sirtuins in kidney diseases, especially their role in podocyte injury, and summarizes the possible rationale for sirtuins as targets for pharmacological intervention in podocyte injury-related glomerular diseases.

足细胞损伤是肾脏疾病蛋白尿的主要原因，足细胞的持续丢失导致肾脏疾病快速不可逆的进展。Sirtuins 是一类烟酰胺腺嘌呤二核苷酸依赖性脱乙酰酶，可促进 DNA 修复、修饰转录因子和调节细胞周期。此外，sirtuins 在肾脏保护中发挥关键作用，特别是防止足细胞损伤。它们还对足细胞损伤相关的肾小球疾病具有多效保护作用，例如改善免疫炎症状态和氧化应激水平、维持线粒体稳态、增强自噬和调节脂质代谢。Sirtuins 缺乏会导致不同肾小球疾病中的足细胞损伤。使用足细胞沉默调节蛋白特异性敲除和转基因模型的研究证实了这一结论。值得注意的是，sirtuin 激活剂对不同的足细胞损伤相关肾小球疾病具有保护作用，包括糖尿病肾病、局灶节段性肾小球硬化、膜性肾病、IgA 肾病和狼疮性肾炎。这些发现表明，sirtuins 是预防足细胞损伤的有希望的治疗靶点。本综述概述了 sirtuins 在肾脏疾病中作用的最新进展，特别是它们在足细胞损伤中的作用，并总结了 sirtuins 作为药物干预足细胞损伤相关肾小球疾病靶点的可能原理。包括糖尿病肾病、局灶节段性肾小球硬化、膜性肾病、IgA肾病和狼疮性肾炎。这些发现表明，sirtuins 是预防足细胞损伤的有希望的治疗靶点。本综述概述了 sirtuins 在肾脏疾病中作用的最新进展，特别是它们在足细胞损伤中的作用，并总结了 sirtuins 作为药物干预足细胞损伤相关肾小球疾病靶点的可能原理。包括糖尿病肾病、局灶节段性肾小球硬化、膜性肾病、IgA肾病和狼疮性肾炎。这些发现表明，sirtuins 是预防足细胞损伤的有希望的治疗靶点。本综述概述了 sirtuins 在肾脏疾病中作用的最新进展，特别是它们在足细胞损伤中的作用，并总结了 sirtuins 作为药物干预足细胞损伤相关肾小球疾病靶点的可能原理。