Combination Therapies to Treat Hypertensive Patients with CKD

The need for combination therapy in hypertensive patients with chronic kidney disease (CKD) should require no elaboration. This is particularly true when considering the need to achieve the lower blood pressure goals (<130/80 mmHg) recommended by most guidelines for patients with CKD. Mean number of antihypertensives required to achieve this blood pressure goal in renal outcome trials is between 3.5 and 4 agents. However, the benefit of inhibitors of renin angiotensin system (RAS) shown in multiple renal outcome trials makes their inclusion in the antihypertensive regimen in hypertensive patients with CKD obvious. Adequate diuresis is required to achieve blood pressure goal. In addition, in the ALLHAT trial, the thiazide‐type diuretic, chlorthalidone, was found to be at least as effective as the ACE inhibitor, lisinopril, in slowing progression of renal disease regardless of diabetic status (including the metabolic syndrome) and stage of kidney disease. Although calcium channel blockers in renal outcome trials have been shown to be less effective than RAS inhibitors in slowing the progression of CKD, their efficacy in blood pressure lowering generally requires their inclusion in the regimen. In addition, no loss of renal protection is seen when they are combined with RAS inhibitors. In those with estimated GFR < 40 ml/min/1.73m 2 , loop diuretics should replace thiazide‐type diuretics in antihypertensive drug combinations, though indapamide and metolazone may retain some efficacy if volume status is not an issue. While some earlier studies suggested additive benefit of multiple RAS inhibitors on renal outcomes, recent large renal outcome trials have failed to confirm this benefit.