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November 29, 2021 - Patients with chronic kidney disease retain sodium and fluid, and this causes their blood pressure to rise. Current guidelines state that thiazide diuretics are not as effective in patients with a GFR < 30 ml/min, and loop diuretics are preferred. This guidance has never been confirmed in a randomized controlled trial.

A small study (N=160) published in the NEJM looked at the effects of chlorthalidone, an old thiazide diuretic, in patients with hypertension and stage 4 kidney disease (GFR < 30 ml/min). Patients were randomized to chlorthalidone 12.5 - 50 mg once daily (average study dose 23.1 mg) or placebo. Sixty percent of the patients in the study were also receiving loop diuretics. The primary outcome was change in 24-hour ambulatory systolic blood pressure (SBP) from baseline to 12 weeks. In the chlorthalidone group, average SBP decreased by 11 mmHg compared to 0.5 mmHg in the placebo group. Chlorthalidone-treated patients also had a 52% reduction in the spot albumin-to-creatinine ratio compared to 4% with placebo. NT-proBNP levels decreased by 30% in the chlorthalidone group and by 11% in the placebo group. Side effects were typical of what is expected with thiazide diuretics. In subgroup analysis, loop diuretic use had no significant effect on SBP reduction. [SH review]

Even though this study was short and small, its results are intriguing. Guidelines from the National Kidney Foundation contend that loop diuretics are preferred when the GFR falls below 30 ml/min because thiazides are not as effective. This study clearly contradicts that. Not only did chlorthalidone lower SBP by 11 mmHg, it also reduced proteinuria and NT-proBNP levels. Given the difficulty in treating chronic kidney disease, a cheap and effective drug like chlorthalidone would be a blessing. Long-term studies are needed to evaluate hard outcomes.


Thiazide diuretic review

KDIGO 2021 blood pressure recommendations in CKD