Supratherapeutic Doses of Angiotensin Receptor Blockers to Decrease Proteinuria in Patients with Chronic Kidney Disease

An important endpoint in treating chronic kidney disease, a prevalent disease that can lead to kidney failure and cardiovascular disease, is reducing proteinuria. Proteinuria is an independent risk factor for disease progression and the development of cardiovascular disease and is a key factor that can be used to guide therapy designed to maximize kidney protection. Proteinuria is targeted by using pharmacologic agents that suppress the renin-angiotensin-aldosterone system (RAAS), a regulator of intravascular volume and blood pressure; this has been shown to decrease proteinuria, slow disease progression, and improve coronary disease outcome, independent of effects on blood pressure. The efficacy of RAAS blockers, including angiotensin receptor blockers and angiotensin-converting enzyme inhibitors, may be limited by currently recommended doses, which are based on treatment of hypertension. Data are now emerging from clinical trials demonstrating that use of 'supratherapeutic doses' (doses greater than those approved for lowering blood pressure), compared with standard doses, has favorable safety, tolerability, and efficacy in reducing proteinuria in both diabetic and nondiabetic patients with chronic kidney disease. Supratherapeutic dosing may be a valuable approach for optimizing RAAS blockade and providing renoprotection.