Emerging role of autophagy in kidney function, diseases and aging

TL;DR: Tight glucose control significantly decreases DKD incidence, indicating that hyperglycemia-induced metabolic alterations, including changes in energy utilization and mitochondrial dysfunction, play critical roles in disease initiation.

TL;DR: Changes with normal aging are still of clinical significance, but the elderly have less kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.

TL;DR: 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.

Abstract: Diabetic kidney disease is the leading cause of kidney failure worldwide; in the USA, it accounts for over 50% of individuals entering dialysis or transplant programmes. Unlike other complications of diabetes, the prevalence of diabetic kidney disease has failed to decline over the past 30 years. Hyperglycaemia is the primary aetiological factor responsible for the development of diabetic kidney disease. Once hyperglycaemia becomes established, multiple pathophysiological disturbances, including hypertension, altered tubuloglomerular feedback, renal hypoxia, lipotoxicity, podocyte injury, inflammation, mitochondrial dysfunction, impaired autophagy and increased activity of the sodium–hydrogen exchanger, contribute to progressive glomerular sclerosis and the decline in glomerular filtration rate. The quantitative contribution of each of these abnormalities to the progression of diabetic kidney disease, as well as their role in type 1 and type 2 diabetes mellitus, remains to be determined. Sodium–glucose co-transporter 2 (SGLT2) inhibitors have a beneficial impact on many of these pathophysiological abnormalities; however, as several pathophysiological disturbances contribute to the onset and progression of diabetic kidney disease, multiple agents used in combination will likely be required to slow the progression of disease effectively. Multiple pathophysiological disturbances contribute to the onset and progression of diabetic kidney disease (DKD). This Review describes these pathogenic processes and discusses the ability of sodium–glucose co-transporter 2 (SGLT2) inhibitors to correct or improve many of these processes, which are likely to underlie the ability of these agents to slow progression of established diabetic kidney disease.

TL;DR: This Review summarizes recent advances in understanding the physiological functions of autophagy and its possible roles in the causation and prevention of human diseases.

TL;DR: A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.

TL;DR: Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health, and to play a role in cell death.

TL;DR: The physiological consequences of mammalianTORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders.