Adriana Marton, MD, of Klinikum Nürnberg in Germany and Duke-NUS Medical School in Singapore

Adriana Marton, MD

In a phase 2 trial of patients with stage 3 

, 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 

, she discussed what the topline results could not explain and where the analyses go next.

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

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; 

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; 

 < .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.

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:

Marton A, Saffari SE, Rauh M, et al. Water conservation overrides osmotic diuresis during SGLT2 inhibition in patients with heart failure. 

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Investigators will probe acid base metabolism and metabolomics to explain the blood pressure and potassium findings from DapaBalci-Leap.

, adding the investigational mineralocorticoid receptor antagonist (MRA) balcinrenone to dapagliflozin preserved dapagliflozin’s glucosuric effect and increased fractional potassium excretion, findings that may inform how the 2 drug classes are combined.¹

Adriana Marton, MD, of Klinikum Nürnberg in Germany and Duke-NUS Medical School in Singapore, presented the data as a late-breaking poster at the 

 in Denver, Colorado, and discussed the findings in an interview with 

In a phase 2 trial of patients with stage 3 chronic kidney disease (CKD), adding the investigational mineralocorticoid receptor antagonist (MRA) balcinrenone to dapagliflozin preserved dapagliflozin’s glucosuric effect and increased fractional potassium excretion, findings that may inform how the 2 drug classes are combined.¹  Adriana Marton, MD, of Klinikum Nürnberg in Germany and Duke-NUS Medical School in Singapore, presented the data as a late-breaking poster at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado, and discussed the findings in an interview with HCPLive.

Potassium Concerns Limit MRA Use With SGLT2 Inhibitors in CKD

Sodium glucose cotransporter 2 (SGLT2) inhibitors have improved CKD care and slowed progression, but many patients continue to lose kidney function. MRAs offer cardiorenal protection, and they are increasingly added on top. Marton noted that the steroidal MRA spironolactone lowers blood pressure more than newer nonsteroidal agents but also raises potassium more.

“The problem is that the potassium elevation with MR antagonists is often a reason why they are not prescribed in chronic kidney disease,” Marton said. “There is an idea based on the physiology that combining an SGLT2 inhibitor with an MRA would increase potassium excretion in the urine and therefore would lower the risk of potassium elevation with MRAs. But it has never really been studied or measured.”

To address this gap in research, DapaBalci-Leap tested whether balcinrenone interferes with the solute and water excretion profile of dapagliflozin. The trial compared each agent alone and in combination against placebo. Marton noted that a placebo arm like this is difficult to include today, since SGLT2 inhibitors have become standard background therapy in CKD trials.

DapaBalci-Leap Design: Balcinrenone, Dapagliflozin, and Placebo in Stage 3 CKD

In the investigator-initiated, double-blind, placebo-controlled phase 2 trial, patients with stage 3 CKD were randomized to dapagliflozin 10 mg, balcinrenone 150 mg, the combination, or placebo for 28 days.¹ Participants were >50 years of age,² and Marton said all were naive to both drug classes. Study visits took place at baseline, day 3 for early effects, and day 28 for late effects.

The primary endpoint was the change in glucosuria. Secondary endpoints included urinary water and solute excretion. Blood pressure and plasma potassium were exploratory and safety endpoints.¹

Of 103 randomized patients, 99 completed all visits. The mean estimated glomerular filtration rate (eGFR) was 48.4 mL/min/1.73 m².

Marton noted that the 150 mg balcinrenone dose is greater than the dose in current phase 3 trials. It was the dose recommended for CKD when the study began, and investigators kept it unchanged to preserve the mechanistic design.

Balcinrenone Lowered Systolic Blood Pressure by 14.1 mm Hg

Balcinrenone produced a persistent diuretic effect, caused by transient natriuresis (+0.50 mmol/kg/d; 95% CI, 0.17–0.83; P < .01) with sustained urine dilution. Balcinrenone reduced systolic blood pressure by 14.1 mm Hg (95% CI, 8.0–20.2; P < .001).¹

Dapagliflozin caused persistent glucosuria, which increased urine volume only transiently. Adaptive urine concentration eliminated the osmotic diuretic effect of the SGLT2 inhibitor.¹

Combination Preserved Glucosuria and Increased Fractional Potassium Excretion

Combination therapy fully preserved the glucosuric effect of dapagliflozin at day 3 (+1.28 mmol/kg/d; 95% CI, 0.98–1.57; 

 < .001) and day 28 (+1.22 mmol/kg/d; 95% CI, 0.86–1.59; 

 < .001).¹ Fractional potassium excretion increased by 3.1% (95% CI, 0.81–5.35; 

Dapagliflozin’s urine-concentrating effect overrode the diuretic, urine-diluting effect of balcinrenone, while the blood pressure reduction with balcinrenone was preserved.¹ Marton said plasma potassium rose mildly with the combination. By her calculation, blood pressure fell by about 4.7 mm Hg for every 0.1 mmol/L increase in plasma potassium.

“This blood pressure lowering effect is basically coupled with a very mild and, I think, completely manageable increase in plasma potassium levels,” Marton said. “This ratio is something that has not really been seen with other drugs in this class.”

All treatments were well tolerated. One hyperkalemia event occurred in the balcinrenone group, in a patient with diarrhea and prerenal acute kidney injury (AKI).¹ Investigators plan further analyses of the mechanisms behind the blood pressure and potassium findings.

Editors’ Note: The trial was funded by AstraZeneca. 

A study to investigate the mechanistic effects of dapagliflozin alone or in combination with balcinrenone, compared to balcinrenone and placebo, on body fluid and electrolyte handling and energy metabolism in participants over 50 years of age with chronic kidney disease. ClinicalTrials.gov identifier: NCT05884866. Accessed October 26, 2026. 

https://clinicaltrials.gov/study/NCT05884866

Balcinrenone lowered systolic BP by 14.1 mm Hg in stage 3 CKD, while combination therapy preserved dapagliflozin's glucosuric effect.

Adriana Marton, MD

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