[From the molecular genetics of Alport's syndrome to principles of organo-protection in chronic renal diseases].
BACKGROUND
Scarring is known to be the endpoint of most chronic kidney diseases. Therefore, prevention of renal fibrosis is a very important topic. The hereditary type IV collagen disease Alport's syndrome is a rare, but challenging cause of chronic renal fibrosis.
Increasing knowledge about the pathogenesis of Alport's syndrome may help to find principles of nephro-protection in chronic renal diseases. The defect gene in Alport's syndrome causes an altered assembly of extracellular matrix leading to a defect cell-matrix interaction and fibrosis. This scarring is regulated by comparable mechanisms as in diabetic nephropathy or chronic inflammatory renal diseases. NEPHRO-PROTECTION IN ANIMAL MODELS: By using an Alport animal model of chronic renal fibrosis, principles of nephro-protective therapies such as blockade of the renin-angiotensin system or the effect of HMG-CoA reductase inhibitors can be investigated. CURRENT AND FUTURE NEPHRO-PROTECTION IN HUMANS: The same model serves for evaluation of new organo-protective therapies such as vasopeptidase inhibitors, blockade of endothelin, chemokine and collagen receptors as well as stem cell therapy and their potential benefit for patients with chronic renal diseases.
Gross
Oliver
O
Medizinische Klinik I Kliniken der Stadt Köln gGmbH, Krankenhaus Merheim, Medizinische Fakultät der Universität zu Köln, Ostmerheimer Strasse 200, 51109 Köln. oliver.gross@uni-koeln.de
Weber
Manfred
M
D000818:Animals; D024141:Collagen Type IV / Q000235:genetics*; D004195:Disease Models, Animal; D050533:Glomerular Basement Membrane / Q000473:pathology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008854:Microscopy, Electron; D008967:Molecular Biology; D009394:Nephritis, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009395:Nephritis, Interstitial / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D009400:Nephrosclerosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D020011:Protective Agents / Q000627:therapeutic use*
D024141:Collagen Type IV; D020011:Protective Agents