Combination therapy in chronic kidney disease?

The renin-angiotensin system (RAS) plays a fundamental role in preserving the circulation and yet, it may be injurious to heart and blood vessels and may also allow, and sometimes hasten, kidney disease progression. Thus, effective RAS inhibition may be a major pharmacologic necessity to control hypertension, to decrease cardiovascular complication, and to inhibit kidney disease progression. Unfortunately, the beneficial effects attained in the management of renal disease sometimes are incomplete. The reasons for these inadequate outcomes may include angiotensin escape or excessive local angiotensin production. Two pharmacologic strategies have been proposed to overcome this drawback including higher than recommended doses of RAS inhibitors and the combination of two different RAS inhibitors. However, three large studies have shown that these more intensive pharmacologic approaches should be treated with caution when applied to high-risk patients, as organ perfusion may fall to critical levels that may cause severe complications. Nevertheless, intensive RAS inhibition (including combination therapy) may be the sole alternative in patients with chronic kidney disease (CKD) in whom other therapeutics options have failed. In these cases, adequate precautions including close clinical and laboratory follow up should prevent major complications.