title: Podocyte dysfunction in aging--related glomerulosclerosis.
abstract: We review podocyte molecular structure and function, consider the underlying mechanisms related to podocyte dysfunction and propose that podocyte dysfunction be considered in the evaluation and management of age-associated glomerulosclerosis. With aging, progressive sympathetic activation, increased intrarenal renin-angiotensin system (RAS) activity, endothelin system and oxidative stress and reduced nitric oxide (NO)-availability can damage podocytes. Apoptosis and proliferation are the principal podocyte changes following injury with the latter leading to sclerosis and loss of nephrons. Podocyte loss can be evaluated by either determining their average number in biopsed glomeruli or by estimating podocyte number or their associated molecules in urine sediment. Podocyturia may be considered a marker of active glomerular disease. Preliminary data suggest that antiadrenergic drugs, angiotensin converting enzyme (ACE) inhibitors, RAS blocking drugs, endothelin system inhibitors and reduced oxidative stress can protect podocytes. Thus podocytes appear to play an important role in the pathogenesis, evaluation and therapy of age related glomerulosclerosis.
authors.affiliation: Department of Internal Medicine, Pisa University, Pisa, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Camici
authors.forename: Angelo
authors.initials: A
authors.lastname: Carpi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cini
authors.forename: Fabio
authors.initials: F
authors.lastname: Galetta
authors.forename: Nader
authors.initials: N
authors.lastname: Abraham
mesh_terms: D018674:Adrenergic Antagonists / Q000627:therapeutic use; D000375:Aging / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology*; D016232:Endothelins / Q000037:antagonists & inhibitors; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D018674:Adrenergic Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016232:Endothelins; D009569:Nitric Oxide