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.