Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Kidney Int. 2010 Apr;77(7):571-80. doi: 10.1038/ki.2009.424. Epub 2009 Nov 18.
Proteinuria is a major health-care problem that affects several hundred million people worldwide. Proteinuria is a cardinal sign and a prognostic marker of kidney disease, and also an independent risk factor for cardiovascular morbidity and mortality. Microalbuminuria is the earliest cue of renal complications of diabetes, obesity, and the metabolic syndrome. It can often progress to overt proteinuria that in 10-50% of patients is associated with the development of chronic kidney disease, ultimately requiring dialysis or transplantation. Therefore, reduction or prevention of proteinuria is highly desirable. Here we review recent novel insights into the pathogenesis and treatment of proteinuria, with a special emphasis on the emerging concept that proteinuria can result from enzymatic cleavage of essential regulators of podocyte actin dynamics by cytosolic cathepsin L (CatL), resulting in a motile podocyte phenotype. Finally, we describe signaling pathways controlling the podocyte actin cytoskeleton and motility and how these pathways can be manipulated for therapeutic benefit.
蛋白尿是一个主要的医疗保健问题，影响着全球数亿人。蛋白尿是肾脏疾病的一个主要标志和预后标志物，也是心血管发病率和死亡率的一个独立危险因素。微量白蛋白尿是糖尿病、肥胖和代谢综合征肾脏并发症的最早线索。它通常会进展为显性蛋白尿，在 10-50%的患者中与慢性肾脏病的发展相关，最终需要透析或移植。因此，减少或预防蛋白尿是非常可取的。在这里，我们回顾了蛋白尿发病机制和治疗的最新新见解，特别强调了一个新出现的概念，即蛋白尿可能是由于胞质组织蛋白酶 L (CatL)对足细胞肌动蛋白动力学的必要调节剂进行酶切导致的，从而产生一个可移动的足细胞表型。最后，我们描述了控制足细胞肌动蛋白细胞骨架和运动的信号通路，以及如何操纵这些通路以获得治疗益处。
