Progress has been made in our understanding of the mechanisms of endoplasmic reticulum (ER) proteostasis, ER stress and the unfolded protein response (UPR), as well as ER stress-induced autophagy, in the kidney. Experimental models have revealed that disruption of the UPR, including a protein that senses misfolded proteins (namely, inositol-requiring enzyme 1α) in mouse podocytes causes podocyte injury and albuminuria as mice age. Protein misfolding and ER stress are evident in various renal diseases, including primary glomerulonephritides, glomerulopathies associated with genetic mutations, diabetic nephropathy, acute kidney injury, chronic kidney disease and renal fibrosis. The induction of ER stress may be cytoprotective, or it may be cytotoxic by activating apoptosis. The UPR may interact in a coordinated manner with autophagy to alleviate protein misfolding and its consequences. Monitoring the excretion of ER chaperones into the urine can potentially serve as a biomarker of renal ER stress. In specific kidney diseases, the treatment of experimental animals with chemical chaperones that improve protein folding or with chaperone inducers has alleviated kidney injury. Given the limited availability of mechanism-based therapies for kidney diseases, normalization of ER stress using pharmacological agents represents a promising therapeutic approach towards preventing or arresting the progression of kidney disease.

我们对肾脏内质网（ER）蛋白质稳态，ER应激和未折叠的蛋白质反应（UPR）以及ER应激诱导的自噬的机理的理解已取得进展。实验模型表明，UPR的破坏（包括一种感觉到小鼠足细胞中折叠错误的蛋白质（即需要肌醇的酶1α）的蛋白质）会随着小鼠年龄的增长而引起足细胞损伤和蛋白尿。蛋白质错误折叠和内质网应激在各种肾脏疾病中都很明显，包括原发性肾小球磷脂，与基因突变相关的肾小球病变，糖尿病性肾病，急性肾损伤，慢性肾脏病和肾纤维化。内质网应激的诱导可能是细胞保护性的，也可能是通过激活细胞凋亡而具有细胞毒性的。UPR可以与自噬协同作用，以减轻蛋白质错误折叠及其后果。监测ER伴侣分子向尿液中的排泄可以潜在地充当肾脏ER应激的生物标记。在特定的肾脏疾病中，用改善蛋白折叠的化学伴侣或伴侣诱导剂治疗实验动物可减轻肾脏损伤。鉴于针对肾脏疾病的基于机制的疗法的可用性有限，使用药理学手段使内质网应激正常化代表了一种有希望的预防或阻止肾脏疾病进展的治疗方法。用改善蛋白折叠的化学伴侣或伴侣诱导剂治疗实验动物可减轻肾脏损伤。鉴于针对肾脏疾病的基于机制的疗法的可用性有限，使用药理学手段使内质网应激正常化代表了一种有希望的预防或阻止肾脏疾病进展的治疗方法。用改善蛋白折叠的化学伴侣或伴侣诱导剂治疗实验动物可减轻肾脏损伤。鉴于针对肾脏疾病的基于机制的疗法的可用性有限，使用药理学手段使内质网应激正常化代表了一种有希望的预防或阻止肾脏疾病进展的治疗方法。