Inhibition of the Renin-Angiotensin System in Chronic Kidney Disease: A Critical Look to Single and Dual Blockade

The clinical benefits of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) are well established in chronic kidney disease (CKD) patients with diabetic and non-diabetic nephropathies. But despite appearance, the magnitude of this effect has been questioned particularly in mild, proteinuric nephropathies. Given that the single agents can achieve only partial and not durable suppression of the renin-angiotensin system (RAS), it has been hypothesized that dual blockage with ACE inhibitors and ARBs would be most beneficial in the management of progressive CKD than either agent alone. Available evidence indicates significant anti-proteinuric effect, but long-term data in CKD patients are lacking. Recently, the findings of the ONTARGET trial even questioned the safety of this therapeutic approach. Given that preventing cardiovascular complications is extremely important in CKD and RAS inhibition may be useful in this setting, benefits of RAS blockade must be weighed against its possible adverse effects particularly in elderly patients.