Thiazide Diuretics in Chronic Kidney Disease

Widely prevalent in the general population, chronic kidney disease (CKD) is frequently complicated with hypertension. Control of hypertension in this high-risk population is a major modifiable cardiovascular and renal risk factor but often requires multiple medications. Although thiazides are an attractive agent, guidelines have previously recommended against thiazide use in stage 4 CKD. We review the updated guidelines on thiazide use in advanced CKD, the antihypertensive mechanism of thiazides, and the clinical studies of thiazides in CKD. Older uncontrolled studies have shown that metolazone reduces blood pressure in CKD, but more recently small randomized controlled trials of hydrochlorothiazide in CKD have shown significant improvement in mean arterial pressure of 15 mm Hg. Two recent uncontrolled studies of chlorthalidone including one that used ambulatory blood pressure monitoring found significant improvements in blood pressure. These findings all suggest that thiazides may be efficacious even in advanced CKD; however, electrolyte abnormalities were common in the studies reviewed so close monitoring is necessary during use. Adequately powered randomized trials are now needed before the routine use of thiazide diuretics in advanced CKD can be recommended.