Can dual blockade of the renin–angiotensin system reduce progression of kidney disease beyond monotherapy?

It is well-accepted that therapies directed at the renin-angiotensin system (RAS) reduce the progression of chronic kidney disease. Angiotensin-converting enzyme (ACE) inhibitors and the angiotensin receptor blockers (ARBs) are currently available to interrupt this cascade. Their positive actions result from better blood pressure control, a reduction in glomerular capillary pressure and a decrease in proteinuria. Blockade of the RAS may also reduce renal scarring by blunting direct pro-fibrotic effects of angiotensin II and aldosterone. Although these drugs successfully reduce urinary protein excretion and improve renal survival, a significant number of patients continue to progress to end stage renal disease. It is possible, however, that dual blockade of the RAS with an ACE inhibitor and an ARB might offer further benefit beyond using either agent alone. Optimally, the goal should be to completely halt the progression of kidney disease. With these concepts in mind, this paper will review the RAS and its effects on the kidney. The efficacy and safety of dual RAS blockade in proteinuric renal diseases will be examined. Finally, recommendations for utilising combined therapy with ACE inhibitors and ARBs will be provided.