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.