Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetic Kidney Disease: A Multicenter, Open-Label, Prospective Study

Abstract

Introduction: Clinical data of esaxerenone in hypertensive patients with diabetic kidney disease (DKD) are lacking. We evaluated the efficacy and safety of esaxerenone in patients with DKD and an inadequate response to blood pressure (BP)-lowering treatment.

Methods: In this multicenter, open-label, prospective study, patients were divided into urinary albumin-to-creatinine ratio subcohorts (UACR < 30, 30 to < 300, and 300 to < 1000 mg/gCr). Esaxerenone was initiated at 1.25 mg/day and followed by incremental dose escalation based on BP and serum potassium level monitoring. The treatment period was 12 weeks. The primary endpoint was change in morning home systolic BP/diastolic BP (SBP/DBP) from baseline to end of treatment (EOT). Secondary endpoints included achievement rate of target BP, change in UACR from baseline, and safety.

Results: In total, 113 patients were enrolled. Morning home SBP/DBP significantly decreased from baseline to EOT in the total population (- 11.6/- 5.2 mmHg, both p < 0.001) and in all UACR subcohorts (all p < 0.001). The target BP achievement rate was 38.5%. Significant reductions in bedtime home and office BPs were also shown in the total population and all UACR subcohorts. UACR significantly improved from baseline to EOT in the total (- 50.9%, p < 0.001) and all UACR subcohorts (all p < 0.001). Incidence of serum potassium elevation as drug-related treatment emergent adverse events was 2.7%. The change from baseline in estimated glomerular filtration rate (eGFR) was - 4.8 mL/min/1.73 m².

Conclusion: Esaxerenone demonstrated a BP-lowering effect and improved albuminuria. The effects were consistent regardless of the severity of albuminuria without clinically relevant serum potassium elevation and eGFR reduction.

Clinical trial registration: jRCTs06119002.

Keywords: Diabetic kidney disease; Esaxerenone; Hypertension; Mineralocorticoid receptor blocker; Urinary albumin-to-creatinine ratio.

Fig. 1

Change from baseline in morning home BP levels at EOT in the total population (a) and urinary albumin-to-creatinine ratio subcohorts (b), and change from baseline in bedtime home BP level (c) and office BP level (d) (full analysis set). Patients with a urinary albumin-to-creatinine ratio of < 30 mg/gCr, 30 to < 300 mg/gCr, and 300 to < 1000 mg/gCr were assigned to the A1, A2, and A3 subcohorts, respectively. Data are mean [95% confidence interval]. **p < 0.001. BP blood pressure, DBP diastolic blood pressure, EOT end of treatment, SBP systolic blood pressure

Fig. 2

Time course changes (a) and change from baseline (b) in morning home SBP and DBP throughout the study period (full analysis set). Data are mean ± standard deviation. **p < 0.001. BP blood pressure, DBP diastolic blood pressure, EOT end of treatment, SBP systolic blood pressure

Fig. 3

Geometric percentage change in UACR from baseline to EOT in the total population (a) and UACR subcohorts (b) (full analysis set). Patients with a UACR of < 30 mg/gCr, 30 to < 300 mg/gCr and 300 to < 1000 mg/gCr were assigned to the A1, A2, and A3 subcohorts, respectively. Error bars indicate 95% confidence intervals. **p < 0.001. EOT end of treatment, UACR urinary albumin-to-creatinine ratio

Fig. 4

Time course changes in eGFRcreat (a, b) and serum potassium levels (c, d) during the study period in the total population (a, c) and urinary albumin-to-creatinine ratio subcohorts (b, d) (safety analysis set). Patients with a urinary albumin-to-creatinine ratio of < 30 mg/gCr, 30 to < 300 mg/gCr, and 300 to < 1000 mg/gCr were assigned to the A1, A2, and A3 subcohorts, respectively. Data are mean ± standard deviation. eGFRcreat creatinine-based estimate of the glomerular filtration rate