A new experimental drug lowered blood pressure and sharply reduced signs of kidney damage in people with chronic kidney disease.
Baxdrostat, an investigational pill designed to block production of the hormone aldosterone, showed encouraging results in people facing a difficult and dangerous combination: chronic kidney disease and uncontrolled high blood pressure.
In a Phase 2 clinical trial published in the Journal of the American Society of Nephrology, adding baxdrostat to standard treatment lowered systolic blood pressure more than placebo and sharply reduced a urine marker tied to kidney and cardiovascular risk. The findings suggest that the drug may do more than lower blood pressure. It may also help protect the kidneys from further damage.
The results are especially important because chronic kidney disease and high blood pressure often fuel each other. When blood pressure stays high, kidney damage can worsen. As kidney function declines, blood pressure can climb even higher. Over time, this cycle can raise the risk of heart attack, stroke, heart failure, and kidney failure.
A Hormone That Can Drive Blood Pressure and Kidney Damage
Aldosterone is made by the adrenal glands and helps the body regulate salt and water. When levels are too high or poorly controlled, the hormone can cause the body to hold on to sodium, which leads to water retention and higher blood pressure.
Excess aldosterone may also damage blood vessels, contribute to thickening and stiffening in the cardiovascular system, and promote scarring in the kidneys. Because of that, researchers have been studying whether directly lowering aldosterone production could help patients whose blood pressure remains high despite standard medications.
Baxdrostat belongs to a class of drugs known as aldosterone synthase inhibitors. These medicines are designed to reduce the body’s production of aldosterone and are being tested for conditions that include high blood pressure, chronic kidney disease, and heart failure. Baxdrostat has not been approved for any use by the U.S. Food and Drug Administration.
“These findings are encouraging for people living with chronic kidney disease and high blood pressure, two conditions that often go hand-in-hand and create a dangerous cycle,” said lead study author Jamie P. Dwyer, M.D., a professor of medicine in the division of nephrology and hypertension at University of Utah Health in Salt Lake City. “High blood pressure can worsen kidney function, and declining kidney function can further elevate blood pressure, and these outcomes can be life-altering for patients.”
Testing Baxdrostat in High-Risk Kidney Patients
The trial was designed to evaluate whether baxdrostat could safely improve blood pressure control when added to standard care in people with chronic kidney disease and uncontrolled hypertension. The participants had kidney disease serious enough that they were considered likely to face kidney failure or require a transplant during their lifetime.
Their blood pressure remained high even though they were already taking either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). These commonly used medicines act on a hormone system that helps control blood pressure.
At the start of the study, participants had an average systolic (top number) blood pressure of 151 mm Hg despite treatment. Laboratory tests also showed clear evidence of kidney disease. Their average urine albumin level was 714 mg/gm of creatinine. Levels of 30 or higher may signal chronic kidney disease. Their average estimated glomerular filtration rate (eGFR, a key indicator of kidney function) was 44mL/min/1.73. Persistent levels below 60 suggest chronic kidney disease.
The study enrolled 195 people, and 192 were randomly assigned to receive low-dose baxdrostat (0.5 mg-1 mg), high-dose baxdrostat (2 mg-4 mg), or a placebo in addition to standard care. Three people ended participation early because of adverse events, their own decision to leave the study, or other reasons.
Blood Pressure Fell and Kidney Strain Markers Improved
After 26 weeks, participants taking baxdrostat had an average systolic blood pressure reduction that was 8.1 mm Hg greater than those taking placebo. That represented a reduction of about 5%.
The researchers also examined urine albumin in an exploratory analysis. Albumin is a protein that, when found in urine at high levels, can signal elevated risk for kidney and cardiovascular disease. Participants taking baxdrostat had urine albumin levels that were 55% lower than those taking placebo. That reduction was comparable to what has been seen with medications known to slow kidney disease progression.
“The reduction in urine albumin gives us hope that baxdrostat may also help delay kidney damage. This potential is now being tested in two large Phase 3 trials to determine if baxdrostat delays the progression of kidney disease,” said Dwyer.
Safety findings showed that high potassium levels in the blood were much more common among people taking baxdrostat. This is a known concern with medications that affect the renin angiotensin aldosterone system. High potassium occurred in 41% of baxdrostat participants and 5% of placebo participants, with most cases described as mild to moderate.
No deaths or unexpected adverse events occurred during the trial. Serious adverse events were reported in 9% of participants taking baxdrostat and 3% of participants taking placebo.
Why the Findings Matter
Jordana B. Cohen, M.D., M.S.C.E., who was not involved in the study, said the results are notable because people with chronic kidney disease have often been left out of drug studies, even though they face high rates of hypertension and elevated renin angiotensin aldosterone activity.
“These new findings are reassuring that this new class of antihypertensive medications are likely to have both kidney- and cardio-protective benefits and to be safe and effective for broad patient populations,” said Cohen, immediate past chair of the American Heart Association’s Hypertension and Kidney Cardiovascular Science Committee. “Patients with chronic kidney disease were historically often excluded from drug studies. It is particularly reassuring to know that patients with chronic kidney disease, who have very high rates of hypertension and elevated renin-angiotensin aldosterone activity, were represented in their own study, tolerated the medication well, and had both blood pressure and albuminuric benefits. This medication class could be a game changer in the management of hypertension in this patient group.”
Cohen is deputy director and associate professor of medicine and epidemiology in the Perelman School of Medicine at the University of Pennsylvania.
Newer Findings Strengthen the Case for Baxdrostat
Since these kidney-focused findings were reported in September 2025, additional baxdrostat data have added momentum to the drug’s development.
In the Phase 3 BaxHTN trial, published in the New England Journal of Medicine and presented at the European Society of Cardiology Congress 2025, baxdrostat significantly lowered seated systolic blood pressure in people with uncontrolled or resistant hypertension. AstraZeneca reported that the 2 mg dose lowered systolic blood pressure by 15.7 mm Hg from baseline, a 9.8 mm Hg placebo-adjusted reduction, after 12 weeks.
Later results from the Phase 3 Bax24 trial showed that baxdrostat lowered 24-hour ambulatory systolic blood pressure by 14.0 mm Hg compared with placebo in people with resistant hypertension. The study also found a 13.9 mm Hg placebo-adjusted reduction in nighttime systolic blood pressure. AstraZeneca said the results were being shared with regulatory authorities.
For chronic kidney disease specifically, baxdrostat is now being evaluated in combination with dapagliflozin in large Phase 3 studies. One trial is testing the combination in adults with chronic kidney disease and hypertension over a 24 month double blind period, while another renal outcomes study is assessing whether baxdrostat plus dapagliflozin can reduce the risk of major kidney and cardiovascular outcomes, including a sustained decline in eGFR, kidney failure, heart failure events, or cardiovascular death.
These later trials do not yet prove that baxdrostat prevents kidney failure. However, they show that researchers are now testing the bigger question raised by the Phase 2 results: whether lowering aldosterone can translate into long-term kidney and heart protection.
Study Details
The trial included 195 participants with an average age of 66 years. Among them, 32% were women, 40% were non-Hispanic white, and 80% had Type 2 diabetes. The study was conducted at 71 sites in the United States. Three participants were not randomized or included in the final analysis.
All participants had uncontrolled high blood pressure (systolic blood pressure of 140 mm Hg or higher, or 130 mm Hg or higher for people with Type 2 diabetes ) despite taking the maximum tolerated dose of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker among their medications. Their average systolic blood pressure was 151.2 mm Hg at the beginning of the trial.
Participants also had chronic kidney disease, but were not in kidney failure. Eligibility included an eGFR of 25 to 75 mL/min/1.73, with an average eGFR of 44 mL/min/1.73 at the start of the study, and a urine albumin-creatinine ratio of 100 mg/g or higher, with an average of 713.8 at the start of the study.
The 192 randomized participants were assigned to one of three groups: low-dose baxdrostat (0.5 mg/day, increasing to 1 mg/day after two weeks), high-dose baxdrostat (2 mg/day, increasing to 4 mg/day after two weeks), or placebo. After 26 weeks, researchers repeated blood pressure and kidney function testing. The primary analysis compared changes in systolic blood pressure across the three groups, and adverse events were tracked for each group.
Reference: “Efficacy and Safety of Baxdrostat in Participants with CKD and Uncontrolled Hypertension: A Randomized, Double-Blind, Placebo-Controlled Trial” by Jamie P. Dwyer, Noha Maklad, Ola Vedin, John Monyak, Robin Myte, Glenn M. Chertow, Hiddo J.L. Heerspink and Dustin J. Little, 6 September 2025, Journal of the American Society of Nephrology.
DOI: 10.1681/ASN.0000000849
The study was funded by AstraZeneca, the developer of baxdrostat.
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