title: Phosphate and FGF23 in the renoprotective benefit of RAAS inhibition.
abstract: Renin angiotensin-aldosterone system (RAAS) blockade is a mainstay of chronic kidney disease (CKD) treatment given its beneficial effects on proteinuria, nephroprotection, heart disease and global mortality. The FGF23/Klotho/phosphate axis is crucial for phosphate excretion. During CKD, loss of Klotho, decreased phosphate excretion and FGF23 elevation are early events contributing both to renal disease progression and to cardiovascular complications. Experimental evidence suggests that Klotho replacement may improve renal and cardiovascular disease during CKD. Recent evidence suggests that both RAAS activation and proteinuria decrease Klotho expression and lead to phosphate retention and FGF23 elevation. In opposition RAAS blockade may reverse Klotho loss during CKD in both experimental and human studies, with direct and indirect expected beneficial effects on the kidney and cardiovascular system. This effect of RAAS blockade on the FGF23/Klotho/phosphate axis may participate in explaining some of the beneficial effects of these drugs during CKD. In this article we review the evidence linking RAAS blockade to modulation of the FGF23/Klotho/phosphate axis and the beneficial effects of these regulations.
authors.affiliation: Service of Nephrology, Department of Medical Specialties, University Hospital of Geneva and University of Geneva, Switzerland; Laboratory of Nephrology, Department of Medicine Specialties and PHYME Department, University of Geneva, Switzerland. Electronic address: Sophie.deseigneux@hcuge.ch.
authors.forename: Sophie
authors.initials: S
authors.lastname: de Seigneux
authors.affiliation: Service of Nephrology, Department of Medical Specialties, University Hospital of Geneva and University of Geneva, Switzerland; Laboratory of Nephrology, Department of Medicine Specialties and PHYME Department, University of Geneva, Switzerland.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Martin
mesh_terms: D000818:Animals; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D000090265:Klotho Proteins; D010710:Phosphates / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Ace inhibitors; Chronic kidney disease; FGF23; Klotho; Phosphate; RAA system