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Can Chlorthalidone Lower Blood Pressure in Patients with Advanced Kidney Disease?

Literature published decades ago suggested that thiazide diuretics lose their antihypertensive effects in patients with advanced chronic kidney disease (CKD). Consequently, many of us were taught to discontinue thiazides when serum creatinine levels exceeded roughly 2 mg/dL. However, more-recent data indicate that thiazides might lower blood pressure (BP) even in patients with substantially impaired renal function.

In this trial, researchers randomized 160 patients with hypertension and stage 4 CKD (mean estimated glomerular filtration rate, 23 mL/minute/1.73 m2) to receive either the thiazide-like diuretic chlorthalidone or placebo. Enrollment criteria included 24-hour ambulatory BP of 130 to 160 mm Hg (systolic) or 80 to 100 mm Hg (diastolic) while receiving antihypertensive therapy. All patients were taking an angiotensin-converting–enzyme inhibitor, angiotensin-receptor blocker, or β-blocker, and most were taking a calcium-channel blocker; patients on high-dose loop diuretics were excluded. The starting dose of chlorthalidone was 12.5 daily and could be titrated as high as 50 mg daily, if needed.

At 12 weeks, mean systolic BP fell by 11 mm Hg in the chlorthalidone group and was unchanged in the placebo group (a significant difference); for diastolic BP, the between-group difference was 4 mm Hg. The average chlorthalidone dose at 12 weeks was about 25 mg. No serious adverse events occurred, but chlorthalidone recipients were more likely to have hypokalemia, hyperuricemia, and hyperglycemia.

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