What Drives Balcinrenone’s BP Effect? With Adriana Marton, MD

In a phase 2 trial of patients with stage 3 chronic kidney disease (CKD), the blood pressure reduction with the investigational mineralocorticoid receptor antagonist (MRA) balcinrenone was sustained despite transient natriuresis and held even when dapagliflozin abolished its diuretic effect, a pattern the trial’s lead investigator says may point to mechanisms beyond sodium and water loss.¹

Adriana Marton, MD, the trial’s principal investigator at Klinikum Nürnberg in Germany and Duke-NUS Medical School in Singapore, presented the late-breaking data at American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado. In an interview with HCPLive, she discussed what the topline results could not explain and where the analyses go next.

Blood Pressure Lowering With MRAs and SGLT2 Inhibitors in CKD

MRAs and sodium glucose cotransporter 2 (SGLT2) inhibitors are both used for cardiorenal protection in CKD, and their blood pressure effects are commonly thought to involve sodium and water loss. DapaBalci-Leap randomized 103 patients to dapagliflozin 10 mg, balcinrenone 150 mg, the combination, or placebo for 28 days.¹

Balcinrenone reduced systolic blood pressure by 14.1 mm Hg (95% CI, 8.0–20.2; P < .001), and the reduction was preserved with the combination.

Blood Pressure Reduction Persisted After Natriuresis Resolved

Balcinrenone caused transient natriuresis, which Marton said was offset by 1 month through activation of the renin angiotensin aldosterone system (RAAS). With dapagliflozin, greater copeptin levels and lower free water clearance pointed to water conservation by the kidneys. Marton described these day 28 effects as physiological adaptations to each drug’s initial action.

“Blood pressure is lowest at 1 month, when the urine volume is back to baseline and there is no more natriuresis,” Marton said. “That means that blood pressure is not really a result of sodium and water loss. It is something else that is going on there.”

Unexplained Plasma Potassium Rise Points Beyond the Kidney

The combination increased fractional potassium excretion by 3.1% (95% CI, 0.81–5.35; P < .01).¹ Marton said total urinary potassium excretion did not change in any arm, yet plasma potassium rose mildly. She said renal potassium handling does not explain the rise.

Investigators will next examine acid base metabolism, including pH, bicarbonate, and ammonium excretion, along with glutamine metabolism. They will also test whether a shift of potassium between the intracellular and extracellular compartments is responsible.

Metabolomics and Comparison With DAPA-Shuttle1

Metabolomic analyses of the urea cycle will explore the strong water conservation response with dapagliflozin, which persisted in the combination arm. Investigators also plan comparisons with DAPA-Shuttle1, Marton’s earlier placebo-controlled trial of dapagliflozin in patients with heart failure.²

Marton noted the kidney plays a central role in water conservation and metabolic adjustment to SGLT2 inhibitors, making the comparison between heart failure and CKD informative.

Patient Commitment Behind Mechanistic Data

Marton said participants attended 5 visits over 2 months, including three 24 hour urine collections, and credited their commitment for the quality of the data.

“If they had not collected their urines properly and they had not attended every visit, we would not have this data now,” Marton said.

Editors’ Note: The trial was funded by AstraZeneca.

References

1. Marton A, Rauh M, Kraetsch HG, et al. Electrolyte, water, and blood pressure homeostasis with balcinrenone and dapagliflozin in patients with CKD: the DapaBalci-Leap trial. Late-breaking abstract TH-PO1237. Presented at: American Society of Nephrology Kidney Week 2026; October 21–25, 2026; Denver, Colorado. doi:10.1681/ASN.20263wzapwqz

2. Marton A, Saffari SE, Rauh M, et al. Water conservation overrides osmotic diuresis during SGLT2 inhibition in patients with heart failure. J Am Coll Cardiol. 2024;83(15):1386-1398. doi:10.1016/j.jacc.2024.02.020