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Control pressure blood pressure in patients with chronic kidney disease is a complex task. The use of certain drugs is reinforced by clinical practice, but without statistical evidence. An example of this is the use of thiazide diuretics (also including thiazide-like diuretics in this class), such as Chlorthalidone, which reduces cardiovascular morbidity and mortality. However, the efficacy and safety of this medication have few studies in relation to patients with advanced chronic kidney disease.
Less robust studies suggest the ability to control blood pressure in patients with advanced chronic kidney disease and the reduction of albuminuria when using chlorthalidone, evidencing its cardio and nephroprotective effect. In December 2021, a randomized clinical trial was published to investigate these effects in the New England Journal of Medicine
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Also read: Rapid test for the diagnosis of chronic kidney disease is on the way
Study designThis is a randomized, double-blind clinical trial, where patients with advanced chronic kidney disease (stage 4) and poorly controlled arterial hypertension were divided into two groups. The intervention group received chlorthalidone (12.5 mg/day, increased every four weeks, up to a maximum dose of 50 mg/day) and the control group received placebo. The primary endpoint was the change in ambulatory systolic blood pressure from the first 24 hours to 12 weeks after starting medication. Secondary outcomes were: urinary albumin/creatinine ratio, serum level of n-terminal pro-B-type natriuretic peptide, plasma renin and aldosterone levels, and total body volume. Security has also been evaluated.
Results
A total of 160 patients were randomized (81 in the intervention group and 79 in the control group), of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. The mean estimated glomerular filtration rate was 23.2 ml/min/1.73 m² of body surface (± 4.2 standard deviation ) and the mean number of antihypertensive drugs prescribed was 3.4 (± 1.4 SD). Mean 24-hour ambulatory systolic blood pressure was 142.6 mmHg (± 8.1 SD) in the Chlorthalidone group and 140.1 mmHg (± 8.1 SD) in the placebo group.
The adjusted change in systolic blood pressure from baseline to 12 weeks later was -11.0 mmHg (95%CI, -13.9 to -8.1) in the Chlorthalidone group and -0 .5 mmHg (95%CI,−3.5 to 2.5) in the placebo group. The difference between the groups was -10.5 mmHg (95%CI, -14.6 to -6.4; p albumin /urinary creatinine from baseline to 12 weeks was lower in the chlorthalidone group than in the placebo group by 50% (95%CI, 37-60%). The occurrence of adverse events such as hypokalemia, hypomagnesaemia, hyponatremia, reversible increases in serum creatinine level, hyperglycemia, dizziness and hyperuricemia were more common in the chlorthalidone group than in the placebo group.
Practical message The conclusion of the study is that “among patients with advanced chronic kidney disease and hypertension, use of chlorthalidone improved blood pressure control at 12 weeks when compared to placebo.”
Some details that call attention: the lowest dose of Chlorthalidone ensured a better therapeutic effect with less occurrence of side effects, as already pointed out in relation to Hydrochlorothiazide; the study did not include a representative portion of women and Hispanics; the nephroprotective and cardioprotective capabilities of Chlorthalidone would be extremely beneficial to patients with chronic kidney disease.
Physician graduated from Faciplac, Gama-DF ⦁ Residency in Internal Medicine at Hospital de Base of the Federal District ⦁ Routine and care leader for Savie in the Internal Medicine ward of Hospital Santa Helena, Rede D’Or, Brasília-DF ⦁ On duty at the Neurocardiovascular Center, Instituto Hospital de Base of the Federal District .
Study designThis is a randomized, double-blind clinical trial, where patients with advanced chronic kidney disease (stage 4) and poorly controlled arterial hypertension were divided into two groups. The intervention group received chlorthalidone (12.5 mg/day, increased every four weeks, up to a maximum dose of 50 mg/day) and the control group received placebo. The primary endpoint was the change in ambulatory systolic blood pressure from the first 24 hours to 12 weeks after starting medication. Secondary outcomes were: urinary albumin/creatinine ratio, serum level of n-terminal pro-B-type natriuretic peptide, plasma renin and aldosterone levels, and total body volume. Security has also been evaluated.
Results
A total of 160 patients were randomized (81 in the intervention group and 79 in the control group), of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. The mean estimated glomerular filtration rate was 23.2 ml/min/1.73 m² of body surface (± 4.2 standard deviation ) and the mean number of antihypertensive drugs prescribed was 3.4 (± 1.4 SD). Mean 24-hour ambulatory systolic blood pressure was 142.6 mmHg (± 8.1 SD) in the Chlorthalidone group and 140.1 mmHg (± 8.1 SD) in the placebo group.
The adjusted change in systolic blood pressure from baseline to 12 weeks later was -11.0 mmHg (95%CI, -13.9 to -8.1) in the Chlorthalidone group and -0 .5 mmHg (95%CI,−3.5 to 2.5) in the placebo group. The difference between the groups was -10.5 mmHg (95%CI, -14.6 to -6.4; p albumin /urinary creatinine from baseline to 12 weeks was lower in the chlorthalidone group than in the placebo group by 50% (95%CI, 37-60%). The occurrence of adverse events such as hypokalemia, hypomagnesaemia, hyponatremia, reversible increases in serum creatinine level, hyperglycemia, dizziness and hyperuricemia were more common in the chlorthalidone group than in the placebo group.
Practical message The conclusion of the study is that “among patients with advanced chronic kidney disease and hypertension, use of chlorthalidone improved blood pressure control at 12 weeks when compared to placebo.”
Some details that call attention: the lowest dose of Chlorthalidone ensured a better therapeutic effect with less occurrence of side effects, as already pointed out in relation to Hydrochlorothiazide; the study did not include a representative portion of women and Hispanics; the nephroprotective and cardioprotective capabilities of Chlorthalidone would be extremely beneficial to patients with chronic kidney disease.
Physician graduated from Faciplac, Gama-DF ⦁ Residency in Internal Medicine at Hospital de Base of the Federal District ⦁ Routine and care leader for Savie in the Internal Medicine ward of Hospital Santa Helena, Rede D’Or, Brasília-DF ⦁ On duty at the Neurocardiovascular Center, Instituto Hospital de Base of the Federal District .
The conclusion of the study is that “among patients with advanced chronic kidney disease and hypertension, use of chlorthalidone improved blood pressure control at 12 weeks when compared to placebo.”
Some details that call attention: the lowest dose of Chlorthalidone ensured a better therapeutic effect with less occurrence of side effects, as already pointed out in relation to Hydrochlorothiazide; the study did not include a representative portion of women and Hispanics; the nephroprotective and cardioprotective capabilities of Chlorthalidone would be extremely beneficial to patients with chronic kidney disease.
Physician graduated from Faciplac, Gama-DF ⦁ Residency in Internal Medicine at Hospital de Base of the Federal District ⦁ Routine and care leader for Savie in the Internal Medicine ward of Hospital Santa Helena, Rede D’Or, Brasília-DF ⦁ On duty at the Neurocardiovascular Center, Instituto Hospital de Base of the Federal District .
References:
10.1056/NEJMoa2110730
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The PEBMED Portal is intended for doctors and other health professionals . Our contents inform recent panoramas of medicine.
If you are interested in publishing your curriculum on the internet, connecting with patients and increasing your differentials, create a free profile on AgendarConsulta, PEBMED’s partner site.
If you are interested in more content and courses aimed at medical residency, get to know Medcel, the PEBMED partner site
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