Thiazide Diuretics as Chronic Antihypertensive Therapy in Patients with Severe Renal Disease—Is There a Role in the Absence of Diuresis?

Abstract

OBJECTIVE: To determine whether thiazides have a chronic antihypertensive effect, in the absence of diuresis, in patients with severe renal disease (creatinine clearance <30 mL/min) or in those receiving dialysis. DATA SOURCES: A search was performed in PubMed, CENTRAL, and International Pharmaceutical Abstracts, using MeSH terms and/or key words. MeSH terms included kidney failure, chronic and exploded terms hydrochlorothiazide, renal dialysis, and thiazides. Key words included thiazide*, hydrochlorothiazide, chlorothiazide, chlorthalidone, indapamide, metolazone, methyclothiazide, bendroflumethiazide, hemodialysis, dialysis, kidney failure, renal failure, renal insufficiency, hypertension, vasodilation, vascular, and diuretics. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language publications were evaluated. Studies evaluating the efficacy of thiazides in renal insufficiency or dialysis were limited to those that included blood pressure measurements. Studies were included only if treatment duration was at least 4 weeks to evaluate chronic antihypertensive effects. DATA SYNTHESIS: Thiazide diuretics are associated with a chronic reduction in peripheral vascular resistance secondary to a purported vasodilatory effect. However, few clinical studies have evaluated the chronic antihypertensive efficacy of thiazide and thiazide-like diuretics in patients with severe renal disease or those on dialysis. Agents studied include hydrochlorothiazide, chlorothiazide, indapamide, and metolazone, with results varying by drug and patient population. Hydrochlorothiazide 25–200 mg daily, chlorothiazide 500 mg twice daily, and indapamide 2.5 mg daily provided long-term blood pressure reduction in patients with severe renal disease who were not on dialysis. In studies involving patients on dialysis, hydrochlorothiazide 50 mg daily and metolazone 5 mg daily did not affect blood pressure; however, 1 study suggested that indapamide 2.5 mg daily may confer an antihypertensive effect. All studies were small (≤12 subjects) and had methodological limitations. CONCLUSIONS: Thiazide diuretics may decrease peripheral vascular resistance independent of natriuresis. However, because current clinical data are inconclusive as to the efficacy of these agents at chronically lowering blood pressure in patients with severe renal disease or in those on dialysis, thiazide diuretics cannot be routinely recommended for this indication.