Cheap Diuretic, Chlorthalidone, Drops BP in Advanced Kidney Disease

Mitchel L. Zoler, PhD

November 05, 2021
Twelve weeks of remedy with the thiazide diuretic chlorthalidone caused approximately a median 10 mmHg reduction in systolic blood strain in sufferers with remedy-resistant high blood pressure and superior level four persistent kidney ailment in a randomized take a look at with one hundred sixty sufferers.

Results from the CLICK trial have disproved traditional awareness that thiazide diuretics are useless in sufferers with an anticipated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2.

The findings also seem to cement chlorthalidone’s function as a brand new alternative for decreasing systolic blood strain in sufferers with level four persistent kidney ailment (CKD) (eGFR 15-29 mL/min/1.73m2) who stay hypertensive notwithstanding remedy with numerous antihypertensive agents.

“We had been fooled that thiazide diuretics do not paintings in sufferers with superior CKD, however, chlorthalidone is superb at reducing blood strain on the pinnacle of 3 or 4 different medicinal drugs. It decreased systolic blood strain via way of means of a median of approximately 10 mmHg, a superb result,” stated Rajiv Agarwal, MD, who provided the outcomes throughout digital Kidney Week 2021, backed via way of means of the American Society of Nephrology.

The outcomes had been concurrently posted in The New England Journal of Medicine.

“Treatment of refractory high blood pressure in sufferers with CKD may be very challenging. I assume chlorthalidone could be followed into exercise primarily based totally on those data,” commented F. Perry Wilson, MD, a nephrologist at Yale University in New Haven, Connecticut.

“You do not constantly want section three take a look at to begin to extrude exercise,” Wilson stated, noting that the CLICK trial randomized simply one hundred sixty sufferers and used surrogate endpoints which include systolic blood strain discount and effect on urinary albumin to creatinine ratio (UACR) to evaluate efficacy.

Agarwal agreed that the CLICK trial might be comparable to a section 2 look at, but additionally highlighted chlorthalidone’s exceptionally sensible repute.

Treatment Costs About five Cents a Day
“The actual promise is that you could deal with sufferers for approximately five cents a day,” stated Agarwal, a nephrologist and professor at Indiana University in Indianapolis.

This good deal fee is a characteristic of chlorthalidone’s long-status normal repute because it first obtained US regulatory approval approximately six many years ago. That additionally method clinicians are “very comfortable” prescribing chlorthalidone, stated Wilson.

Tejas Desai, MD, a nephrologist with the America Department of Veterans Affairs, Charlotte, North Carolina, agrees. “Because chlorthalidone is cheap, effortlessly available, and each the occurrence and incidence of CKD level four are high, the consequences of this trial may have wide and instant applicability, he instructed Medscape Medical News.

Paul K. Whelton, MD, professor at Tulane University in New Orleans, Louisiana, and chair of the panel that wrote the 2017 American College of Cardiology/American Heart Association high blood pressure-remedy guideline concurred: “Chlorthalidone is a superb drug, and the fine documented of any diuretic for reducing blood strain.”

“An 11-mmHg discount in blood strain may be very impressive” in sufferers who are “a conventional organization with resistant high blood pressure,” Whelton stated in an interview.

Whelton suggested that the proof did come from a short, 12-week take a look at, however “it is higher than another proof we have” for the efficacy of a brought antihypertensive drug withinside the forms of sufferers studied.

CLICK enrolled sufferers already on a median of three. four blood strain medicinal drugs a day, and notwithstanding that, that they’d a median systolic blood strain of approximately a hundred and forty mmHg, kind of 10 mmHg above their goal.

Halving Proteinuria Compared With Controls Is “the Big Finding”

Another aspect of chlorthalidone’s advantage changed into that 12 weeks of remedy reduce common UACR via way of means of 50 percent factors most of the eighty-one chlorthalidone-dealt with sufferers as compared with the seventy-nine sufferers randomized to placebo.

This impact led Agarwal and associates to signify that remedy with chlorthalidone may produce kidney and cardiovascular protection, speculation that Wilson referred to as “plausible.”

Chlorthalidone’s impact on proteinuria “is the large finding,” Wilson stated in an interview.

A 50% discount “is absolutely important” due to the fact proteinuria is a first-rate danger issue for modern CKD.

“Not an Agent to Prescribe and Forget,” however Few Safety Surprises
Chlorthalidone’s protection profile in CLICK additionally “appears acceptable” and changed into “now no longer surprising,” stated Wilson, even as Whelton referred to as the destructive occasions of remedy “not anything dramatic.”

Agarwal stated that a few clinicians can be hesitant approximately prescribing chlorthalidone, however, he recommended them to embody it, albeit with caution.

Chlorthalidone “isn’t an agent to prescribe and forget. It’s a completely strong drug and also you want to reveal sufferers for complications,” in particular sufferers already on a loop diuretic, Agarwal stated throughout a Kidney Week digital press briefing.

The largest worries middle on fluctuations in serum tiers of a few electrolytes and different components.

In CLICK, 10% of sufferers on chlorthalidone advanced hypokalemia as compared without an instance amongst controls; 23�veloped hypermagnesemia as compared with 16% of controls; and 20% of these on chlorthalidone advanced hyperuricemia as compared with 9% of controls.

CLICK ran at 3 clinical facilities in Indianapolis in 2016-2021. Of the one hundred sixty randomized sufferers, a hundred and forty (88%) finished the 12-week remedy course. The take a look at protocol referred to as for sluggish up-titration of chlorthalidone as wished throughout the remedy section with a beginning dose of 12. five-mg as soon as daily. The common dose sufferers obtained at 12 weeks changed into 23 mg as soon as daily.

CLICK obtained no industrial funding. Agarwal has stated being a representative for numerous drug companies. Wilson and Desai are individuals to Medscape and stated no different applicable monetary relationships. Whelton has stated no applicable monetary relationships.

N Engl J Med. Published online November five, 2021. Abstract

Mitchel L. Zoler is a reporter for Medscape and MDedge primarily based totally withinside the Philadelphia area. @

 

https://www.medscape.com/viewarticle/962402?src=#vp_2

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