Initial Changes in eGFR during Treatment with Balcinrenone and Dapagliflozin
Key result
Balcinrenone/dapagliflozin induces a modest, reversible acute eGFR dip of ~1.7 mL/min/1.73m2 vs dapagliflozin in CKD.
- MD -1.7
- 95% CI -3.5 to -0.01
- n=324
Why the study?
Does balcinrenone/dapagliflozin improve UACR and affect eGFR in adults with chronic kidney disease compared to dapagliflozin alone?
Key Points
- To evaluate acute changes in eGFR following the initiation of balcinrenone combined with dapagliflozin and assess their association with safety and efficacy outcomes.
- Adults with chronic kidney disease (N=324, eGFR 25 to <60 mL/min/1.73m², UACR 100 to <5000 mg/g) receiving background RAS therapy were randomized to balcinrenone/dapagliflozin (15/10 mg or 40/10 mg) or dapagliflozin 10 mg/placebo.
- Acute eGFR changes at 4 weeks post-randomization and 4 weeks post-treatment were evaluated using mixed model repeated measures.
- Participants were categorized by eGFR trajectory (≥10% reduction, >0 to <10% reduction, or increase) to assess concomitant changes in systolic blood pressure, UACR, and safety events.
- Relative to dapagliflozin/placebo, the acute week 4 eGFR reduction was -0.6 mL/min/1.73m² (95% CI: -2.4, 1.1) with balcinrenone/dapagliflozin 15/10 mg and -1.7 mL/min/1.73m² (95% CI: -3.5, -0.01) with 40/10 mg.
- The initial eGFR reductions fully reversed 4 weeks after treatment discontinuation across all subgroups.
- Greater initial eGFR reductions correlated with larger drops in systolic blood pressure and UACR, while rates of serious adverse events remained low and comparable across groups.
Study Design
Type
RCT (n=324)
Randomization
randomized
Structured PICO
Does balcinrenone/dapagliflozin improve UACR and affect eGFR in adults with chronic kidney disease compared to dapagliflozin alone?
P
Population
324 adults with chronic kidney disease (eGFR 25 to <60 mL/min/1.73m2 and UACR 100 to <5000 mg/g) treated for 12 weeks.
I
Intervention
Balcinrenone/dapagliflozin 15/10 mg or 40/10 mg as adjunct to renin-angiotensin-system therapy
C
Comparator
Dapagliflozin 10 mg/placebo as adjunct to renin-angiotensin-system therapy
O
Outcome
Relative change in UACR from baseline over 12 weekssurrogate
Main Result
Mean Difference: -1.7 (95% CI -3.5–-0.01)
In adults with CKD, adding balcinrenone to dapagliflozin induces a modest, reversible acute eGFR reduction that is associated with greater UACR and SBP lowering without increasing adverse events.
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The patients who are likely to benefit from this [combination] particularly are those patients who are already treated with an SGLT2 inhibitor who have ongoing albuminuria. These patients are still at high risk of progressing to kidney failure.”
“We found that 12 weeks of treatment with balcinrenone at either 15 milligrams or 40 milligrams, combined with dapagliflozin 10 milligrams, significantly reduced urinary albumin to creatinine ratio compared to dapagliflozin alone in people with CKD Stage III to IV. These patients with significantly advanced CKD are at risk of progression to kidney failure, and the results were consistent across all sub-groups that that included type 2 diabetes status, baseline eGFR, baseline urine albumin-to-creatinine ratio and use of SGLT-2 inhibitors.”
Implication
Modest reversible eGFR dip supports short-term safety of balcinrenone/dapagliflozin in CKD; extends phase 2 evidence for combination use.
Abstract
Introduction: The novel non-steroidal mineralocorticoid receptor antagonist balcinrenone in combination with dapagliflozin reduced urinary albumin-to-creatinine ratio (UACR) over 12 weeks in the MIRO-CKD phase 2 trial in chronic kidney disease (CKD) and induced a modest acute eGFR reduction upon treatment initiation. This pre-specified analysis explored the acute eGFR changes in response to balcinrenone/dapagliflozin and the association of these acute eGFR changes on safety and efficacy parameters. Methods: Adults with CKD (n=324, eGFR ≥25 to <60 mL/min/1.73m 2 ; UACR ≥100 to <5000 mg/g) were randomized to balcinrenone/dapagliflozin 15/10 mg, balcinrenone/dapagliflozin 40/10 mg, or dapagliflozin 10 mg/placebo as adjunct to renin-angiotensin-system therapy. The primary outcome was the relative change in UACR from baseline over 12 weeks. Acute eGFR changes 4 weeks post-randomization and 4 weeks post-treatment were assessed using mixed model repeated measures. We categorized participants according to relative eGFR changes: ≥ 10% reduction (eGFR dip); >0 to <10% reduction; or an eGFR increase. We examined safety and concomitant changes in systolic blood pressure (SBP) and UACR across categories of eGFR changes. Results: Relative to dapagliflozin/placebo, the acute eGFR dip at Week 4 with balcinrenone/dapagliflozin 15/10 mg was -0.6 mL/min/1.73m 2 (95%CI: -2.4, 1.1) and with balcinrenone/dapagliflozin 40/10 mg -1.7 mL/min/1.73m 2 (95%CI -3.5, -0.01). The acute reduction in eGFR with balcinrenone/dapagliflozin was reversible 4 weeks after treatment discontinuation. This finding was consistent across subgroups. In the overall cohort, larger acute eGFR reductions were associated with larger reductions in UACR and SBP across treatment arms. Rates of serious adverse events and adverse events of special interest were low, similar in the balcinrenone/dapagliflozin versus placebo/dapagliflozin group, and unrelated to the acute eGFR change. Conclusion: In adults with CKD, balcinrenone/dapagliflozin induced a modest acute eGFR reduction which was reversible after treatment discontinuation, did not lead to increased rates of adverse events, and was associated with greater SBP and UACR lowering.
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Cite This Study
Heerspink et al. (2026) conducted an RCT in chronic kidney disease (CKD) (n=324). balcinrenone/dapagliflozin vs. dapagliflozin 10 mg/placebo was evaluated on acute eGFR dip at Week 4 (MD -1.7, 95% CI -3.5 to -0.01). Balcinrenone/dapagliflozin 40/ induced a modest, reversible acute eGFR reduction of -1.7 mL/min/1.73m2 relative to dapagliflozin/placebo at 4 weeks in adults with CKD.