Chronic Kidney Disease: A Vicarious Relation to Premature Cell Senescence

Chronic kidney disease (CKD), commonly fostering nonrenal complications, themselves more life threatening than renal pathology, remains enigmatic. Despite more than a century of intense research, therapeutic options to halt or reverse renal disease are rather limited. Recently, similarity between manifestations of progressive CKD and aging kidney has attracted investigative attention that revealed senescent cells and secreting proinflammatory and profibrotic mediators in all renal compartments, even at young age, in patients with kidney maladies. The overlapping features of these categories have been noticed previously and are briefly summarized herein. I propose two hypothetical scenarios for interactive association of kidney diseases and cell senescence, both culminating in progressive deterioration of renal function. Persistence of senescent cells is considered as a critical contributor to this association; and the mechanisms explaining persistence, such as activation of cell cycle regulators, anti-apoptotic stimuli, metabolic aberrations, and their interactions, are discussed. The mutual encroachment of underlying kidney disease and cell senescence bring about the conclusion that both entities merge along the natural history of the disease. This putative interpretation of vicarious relation between cell senescence and CKD may expand the arsenal of pharmacotherapy to include the judicious use of senotherapeutics in the management of renal disease