Chlortalidone and bumetanide in advanced chronic kidney disease: HEBE-CKD Trial

Introduction Current treatment for hypertension and volume overload in chronic kidney disease consists of loop diuretics, nevertheless, chronic use leads to adaptive changes at the distal nephron, which in turn decreases their efficacy. The use of thiazide diuretics could be another treatment option in these patients, notwithstanding, there's not enough evidence to justify their use in this population. Purpose To evaluate the efficacy and safety of treatment with bumetanide plus chlorthalidone in in patients with advanced chronic kidney disease. Methods A double-blind randomized controlled trial was conducted at our hospital. Thirty-two patients with hypertension, chronic kidney disease stage IV/V, and chronic loop diuretic use where divided in two groups. The dual treatment group received bumetanide (4 mg QD) plus chlorthalidone (100 mg QD), while the control group was given bumetanide (4 mg QD) plus placebo, both for twenty-eight days. Systemic blood pressure, bioimpedance, and urinary electrolytes were measured at seven and twenty-eight days of treatment. Results There was a significant decrease of systemic blood pressure in the dual treatment group when compared with the control group; systolic blood pressure −26.1±15.3 vs. −10±23.3 mmHg (p=0.028), diastolic blood pressure −13.5±10.7 vs. −3.4±11.9 mmHg (p=0.018), and mean arterial pressure −18.1±8.7 vs. −5.4±14.3 mmHg (p=0.006). There was also a significant decrease of volume overload in the dual treatment group when compared to the control group; total body water −4.36±3.29 vs. +0.075±1.78 litres (p<0.001), extracellular water −2.55±1.1 vs. +0.150±1.2 litres (p<0.001), and extracellular water to total body water ratio −2.92±4.76 vs. −0.24±1.42 (p=0.039). The treatment group increased its fractional excretion of sodium, while the control group demonstrated an increase, though differences were non-significant. As for adverse effects, there was a non-significant increase of urea and creatinine levels in the dual treatment group when compared with controls. Conclusions In advanced chronic kidney disease plus hypertension patients whose treatment with loop diuretics is insufficient, combined use of bumetanide plus chlorthalidone can be useful for systemic blood pressure and volume overload control. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospital General de México