Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents.
Renal fibrogenesis can be induced by several injury mechanisms in different renal diseases, but ultimately produces identical fibrotic changes in the kidney. Recently, a number of agents that can inhibit extracellular matrix (ECM) accumulation have been studied, suggesting a therapeutic utility in the treatment of fibrotic renal disease. Pirfenidone (PFD) is a small molecule that has shown efficacy in various models of renal damage with progressive disease. The apparent absence of toxicity in PFD suggests that it does not affect the normal ECM turnover. Relaxin, a hormone belonging to the insulin-like growth factor (IGF) family, has antifibrotic properties and has been used for a long time to induce transient remissions in patients with scleroderma. Only recently it has been shown to drastically reduce corticomedular scarring in animal models. Bone morphogenetic protein 7 (BMP-7), a member of the transforming growth factor beta (TGF-beta) superfamily, has been shown to reduce glomerular and interstitial area, and prevent glomerular sclerosis even more effectively than enalapril. Finally, hepatocyte growth factor (HGF), with its multiple biological activities on a wide variety of cells, has an organotrophic role in the regeneration and protection of various organs including the kidney. Both endogenous and exogenous HGF have shown suppressive effects on renal fibrosis and chronic renal damage in various animal models. The inhibition of pathological ECM accumulation and the modulation of fibrotic mechanisms with these new antifibrotic agents is an achievable goal and could confer further benefits beyond the current therapies used in the treatment of chronic renal diseases.
Negri
Armando Luis
AL
Physiology and Biophysics Department, University of Salvador, Buenos Aires, Argentina. negri@casasco.com.ar
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D018450:Disease Progression; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000517:prevention & control; D005919:Glomerular Filtration Rate; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000473:pathology* / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D011379:Prognosis; D011728:Pyridones / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012065:Relaxin / Q000627:therapeutic use*; D018570:Risk Assessment; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011728:Pyridones; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor; D012065:Relaxin; C093844:pirfenidone