Autophagy in kidney disease: Advances and therapeutic potential

Abstract

Autophagy is a highly conserved intracellular catabolic process for the degradation of cytoplasmic components that has recently gained increasing attention for its importance in kidney diseases. It is indispensable for the maintenance of kidney homeostasis both in physiological and pathological conditions. Investigations utilizing various kidney cell-specific conditional autophagy-related gene knockouts have facilitated the advancement in understanding of the role of autophagy in the kidney. Recent findings are raising the possibility that defective autophagy exerts a critical role in different pathological conditions of the kidney. An emerging body of evidence reveals that autophagy exhibits cytoprotective functions in both glomerular and tubular compartments of the kidney, suggesting the upregulation of autophagy as an attractive therapeutic strategy. However, there is also accumulating evidence that autophagy could be deleterious, which presents a formidable challenge in developing therapeutic strategies targeting autophagy. Here, we review the recent advances in research on the role of autophagy during different pathological conditions, including acute kidney injury (AKI), focusing on sepsis, ischemia-reperfusion injury, cisplatin, and heavy metal-induced AKI. We also discuss the role of autophagy in chronic kidney disease (CKD) focusing on the pathogenesis of tubulointerstitial fibrosis, podocytopathies including focal segmental glomerulosclerosis, diabetic nephropathy, IgA nephropathy, membranous nephropathy, HIV-associated nephropathy, and polycystic kidney disease.

Keywords: Acute kidney injury; Autophagy; Chronic kidney disease; Diabetic nephropathy; Podocytes; Tubular epithelial cells; Tubulointerstitial fibrosis.