The aggravating mechanisms of aldosterone on kidney fibrosis.

The renin-angiotensin-aldosterone system (RAS) is a widely known regulator of BP and a determinant of target organ damage. Angiotensin II, the main effector of RAS, is a key mediator of renal injury by increasing intraglomerular capillary pressure and ultrafiltration of plasma proteins and by promoting cell growth and fibroproliferative effects. RAS blockade with inhibitors of RAS is beneficial in slowing progressive loss of renal function in chronic kidney disease. Experimental evidence also indicates that aldosterone, besides being a regulator of extracellular fluid volume and sodium and potassium balance, directly contributes to accelerate renal damage by sustaining cell growth, inflammation, and fibrosis. This occurs through production of growth factors and reactive oxygen species as well as inhibition of extracellular matrix degradation. Attenuation of growth-promoting and fibroproliferative effect of aldosterone may contribute to protection against progressive renal injury. Initial studies that detail the efficacy of aldosterone blockade in animals and humans are encouraging. Nevertheless, further studies in larger populations with longer follow-up are warranted to address more definitely the safety and renoprotective effect of aldosterone antagonism in chronic kidney disease patients.