Christopher D Wiley1. 1. Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94945, USA. cwiley@buckinstitute.org.
Abstract
PURPOSE OF REVIEW: Diabetic kidney disease (DKD) is the leading cause of kidney failure in the USA, representing ~ 44% of all cases of kidney failure. Advancements in both glucose management and inhibitors of the renin-angiotensin system have significantly improved prognosis for individuals with DKD, yet DKD continues to affect 30-40% of people with type 2 diabetes and is still a major predictor of mortality in this population. Thus, new interventions are required to address this significant health burden. RECENT FINDINGS: One potential target for intervention is cellular senescence. Senescence permanently arrests cell division in response to genotoxic, oncogenic, or metabolic stresses-coupled to the secretion of inflammatory cytokines, chemokines, growth factors, proteases, and other molecules that can have potent local and systemic effects. This senescence-associated secretory phenotype (SASP) explains how a relatively small number of senescent cells can promote pathology, and a growing number of degenerative conditions have been found to be caused or aggravated by senescent cells. Many SASP factors are also associated with loss of kidney function. Targeted elimination of senescent cells prevents the development of several degenerative pathologies. Since senescent cells appear in the proximal tubules and podocytes of patients with DKD, they are an appealing target for intervention in these disorders. Here, we review the current literature linking senescence to DKD and speculate on the likely routes to intervention in a clinical setting.
PURPOSE OF REVIEW: Diabetic kidney disease (DKD) is the leading cause of kidney failure in the USA, representing ~ 44% of all cases of kidney failure. Advancements in both glucose management and inhibitors of the renin-angiotensin system have significantly improved prognosis for individuals with DKD, yet DKD continues to affect 30-40% of people with type 2 diabetes and is still a major predictor of mortality in this population. Thus, new interventions are required to address this significant health burden. RECENT FINDINGS: One potential target for intervention is cellular senescence. Senescence permanently arrests cell division in response to genotoxic, oncogenic, or metabolic stresses-coupled to the secretion of inflammatory cytokines, chemokines, growth factors, proteases, and other molecules that can have potent local and systemic effects. This senescence-associated secretory phenotype (SASP) explains how a relatively small number of senescent cells can promote pathology, and a growing number of degenerative conditions have been found to be caused or aggravated by senescent cells. Many SASP factors are also associated with loss of kidney function. Targeted elimination of senescent cells prevents the development of several degenerative pathologies. Since senescent cells appear in the proximal tubules and podocytes of patients with DKD, they are an appealing target for intervention in these disorders. Here, we review the current literature linking senescence to DKD and speculate on the likely routes to intervention in a clinical setting.
Authors: Peter Stenvinkel; Glenn M Chertow; Prasad Devarajan; Adeera Levin; Sharon P Andreoli; Sripal Bangalore; Bradley A Warady Journal: Kidney Int Rep Date: 2021-05-04