Adding the novel non-steroidal mineralocorticoid receptor antagonist (MRA) balcinrenone to dapagliflozin therapy significantly reduces albuminuria in patients with chronic kidney disease (CKD) at risk of progression, according to results from the MIRO-CKD trial.¹

MIRO-CKD was a multicentre, randomised, double-blind, active-controlled, phase 2b trial conducted across 106 sites in 15 countries. The study enrolled 324 adults with an estimated glomerular filtration rate (eGFR) of 25 to <60 mL/min per 1.73 m² and a urine albumin-to-creatinine ratio (UACR) of >100 to ≤5000 mg/g. Participants were already receiving renin-angiotensin system inhibitors where tolerated.²

Patients were randomly assigned (1:1:1) to receive one of three once-daily treatments for 12 weeks: balcinrenone 15 mg plus dapagliflozin 10 mg (n=108), balcinrenone 40 mg plus dapagliflozin 10 mg (n=110), or dapagliflozin 10 mg plus placebo (n=106). The primary efficacy endpoint was the relative change in UACR from baseline to week 12.

The cohort had a mean age of 64.6 years, a mean eGFR of 42.2 mL/min per 1.73 m², and a median UACR of 365 mg/g.

Both combination therapy groups demonstrated superiority in reducing UACR compared with dapagliflozin alone. At week 12, the UACR difference versus the dapagliflozin plus placebo group was –22.8% (90% CI –33.3 to –10.7; p=0.0038) for the balcinrenone 15 mg combination and –32.8% (90% CI –42.0 to –22.1; p<0.0001) for the balcinrenone 40 mg combination.

The combination was well tolerated. Investigator-reported hyperkalaemia occurred in 6% of the balcinrenone 15 mg group, 7% of the balcinrenone 40 mg group, and 5% of the control group. Adverse events of hypotension and other renal events were infrequent, balanced across all groups, and none were classified as serious. Two deaths occurred during the study, both more than 28 days after the last dose of the study drug.

The study investigators concluded that in participants with CKD at increased risk of disease progression, a fixed-dose combination of balcinrenone and dapagliflozin was superior to dapagliflozin alone in reducing albuminuria. They noted that the combination was well tolerated, effects on potassium were minor, and no unexpected safety concerns were identified.

This study was funded by AstraZeneca.

References

1. Heerspink HJL, Cardona JF, Jolly S, et al. Balcinrenone in combination with dapagliflozin compared with dapagliflozin alone in patients with chronic kidney disease and albuminuria: a randomised, active-controlled double-blind, phase 2b clinical trial. Lancet. 2025. https://doi.org/10.1016/S0140-6736(25)02014-8

2. Kidney Disease: Improving Global Outcomes CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105:S117-S314.

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