title: Progression of chronic kidney disease: insights from animal models.
abstract: OBJECTIVE
  Chronic kidney diseases are emerging as a worldwide public health problem. Clarification of the mechanisms underlying progression of proteinuric nephropathies received significant input from the generation of transgenic and knockout animals and from novel approaches to block mediators of injury. Reviewed here are advances in animal models used as a tool to address some relevant questions to the pathophysiology of human chronic nephropathies.
  
  
  RESULTS
  Gene targeting in rodents identified podocyte loss as central event in the development of glomerulosclerosis. The trigger is dysfunction or absence of podocyte molecules that stabilize the slit diaphragm or anchor foot processes to the basement membrane. Sustained injury of the glomerular barrier to proteins is transmitted to the tubulointerstitial compartment leading to inflammation and fibrosis. Blocking NF-kappaB activity and chemokine signals in the kidney effectively interrupts such process. Growth factors produced by tubular cells and inflammatory cells contribute to interstitial fibrogenesis via myofibroblast activation.
  
  
  CONCLUSIONS
  Development of genetically engineered animals and techniques to specifically manipulate cellular mediators has highlighted the determinants of glomerulosclerosis and tubulointerstitial injury. This knowledge will provide basis for novel interventions to protect the podocyte in chronic progressive glomerulopathies and to halt renal scarring and loss of function.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy. zoja@marionegri.it
authors.forename: Carla
authors.initials: C
authors.lastname: Zoja
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D007676:Kidney Failure, Chronic / Q000473:pathology* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D023421:Models, Animal; D050199:Podocytes / Q000166:cytology
chemical_list: D008565:Membrane Proteins; C113267:nephrin