Autophagy in the proximal tubule cell and its role in the progression of chronic kidney disease

Abstract

Chronic kidney disease is a substantial health problem effecting a large portion of the US population. Presence of excess protein, particularly albumin, in the urine of patients with chronic kidney disease is an independent risk factor for cardiovascular disease and progression to end stage renal disease. In addition, excess protein reabsorption in the proximal tubule is sufficient to cause damage to the proximal tubule independent of the initial condition that lead to chronic disease. In the last decade, excess protein reabsorption by the proximal tubule as a result of chronic kidney damage has been shown to cause oxidative and ER stress, cell death, as well as tubule inflammation and fibrosis in the proximal tubule cell. Only recently have two studies investigated the role of autophagy in protein-induced tubule damage. Autophagy is a dynamic catabolic mechanism used to degrade cytosolic elements in times of cell starvation and is an important process in the cell's response to stress. The results of the studies by Wei Jin Liu et al. and Yamahara et. al. provide important first steps to determine whether autophagy of excess protein in proteinuric states prevents proximal tubule cell toxicity and potentially slow the progression of chronic kidney disease (CKD). This thesis will explore the results of these two studies in the context of proximal tubule damage in chronic kidney disease, and discuss the potential for protein autophagy to improve our understanding and treatment of chronic kidney disease.