title: The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease.
abstract: The renin-angiotensin-aldosterone system (RAAS) is a well known regulator of blood pressure (BP) and determinant of target-organ damage. It controls fluid and electrolyte balance through coordinated effects on the heart, blood vessels, and Kidneys. Angiotensin II (AII) is the main effector of the RAAS and exerts its vasoconstrictor effect predominantly on the postglomerular arterioles, thereby increasing the glomerular hydraulic pressure and the ultrafiltration of plasma proteins, effects that may contribute to the onset and progression of chronic renal damage. AII may also directly contribute to accelerate renal damage by sustaining cell growth, inflammation, and fibrosis. Interventions that inhibit the activity of the RAAS are renoprotective and may slow or even halt the progression of chronic nephropathies. ACE inhibitors and angiotensin II receptor antagonists can be used in combination to maximize RAAS inhibition and more effectively reduce proteinuria and GFR decline in diabetic and nondiabetic renal disease. Recent evidence suggests that add-on therapy with an aldosterone antagonist may further increase renoprotection, but may also enhance the risk hyperkalemia. Maximized RAAS inhibition, combined with intensified blood pressure control (and metabolic control in diabetics) and amelioration of dyslipidemia in a multimodal approach including lifestyle modifications (Remission Clinic), may achieve remission of proteinuria and renal function stabilization in a substantial proportion of patients with proteinuric renal disease. Ongoing studies will tell whether novel drugs inhibiting the RAAS, such as the renin inhibitors or the vasopeptidase inhibitors, may offer additional benefits to those who do not respond, or only partially respond, to this multimodal regimen.
authors.affiliation: Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Italy. gremuzzi@marionegri.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Norberto
authors.initials: N
authors.lastname: Perico
authors.forename: Manuel
authors.initials: M
authors.lastname: Macia
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000191:economics / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000191:economics / Q000503:physiopathology*; D000451:Mineralocorticoid Receptor Antagonists; D009393:Nephritis / Q000503:physiopathology; D011110:Polymorphism, Genetic; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D012083:Renin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D023001:Transplantation Tolerance; D000092502:Renin Inhibitors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D012083:Renin; D000092502:Renin Inhibitors