Balcinrenone maintained normal urine potassium excretion in diabetic mice versus reduced excretion with eplerenone, suggesting lower hyperkalemia risk.
Does balcinrenone improve cardiac and renal outcomes with better potassium excretion compared to eplerenone in STZ-induced diabetic male mice?
In a diabetic mouse model, the non-steroidal MR modulator balcinrenone offered similar cardiac and renal protection to eplerenone but maintained better potassium excretion, indicating a potentially lower risk of hyperkalemia.
Absolute Event Rate: 0% vs 0%
Patients with diabetes are disproportionately affected by cardiovascular and kidney disease. Mineralocorticoid receptor antagonists (MRA) show organ protection against cardiovascular and renal injury; however, major side effects including hyperkalaemia and reduced renal function limit their use in individuals with diabetic complications. The non-steroidal MR modulator, balcinrenone, may offer end-organ protection with fewer side effects. We compared responses to balcinrenone and eplerenone delivered from 8 weeks post-induction of streptozotocin (STZ)-induced type 1 diabetes in male mice. RNA-sequencing revealed diabetes induced modulation of immune function, and metabolic and vascular targets in the kidney, which were similarly attenuated by balcinrenone or eplerenone treatment. Urine K+ excretion was lower following eplerenone treatment, but not balcinrenone treatment, compared to diabetes without treatment. We identified a 5.90-fold increase in the expression of K+ transporter G protein-activated inward rectifier potassium channel 1 (GIRK-1) in eplerenone-, but not balcinrenone-treated diabetic mice. Balcinrenone and eplerenone similarly attenuated the diabetes-induced reduction in peak E-wave/A-wave velocity (E/A) compared to mice without treatment at 15 weeks post-STZ. Gene markers of cardiac injury, B-type natriuretic peptide (Bnp) and beta-myosin heavy chain protein (Myh7), were higher in diabetic versus non-diabetic left ventricles (LV). Conversely, gene expression of Ca2+ ion channel subunits, voltage-dependent L type, calcium channel subunit alpha 1C (Cav1.2) and ryanodine receptor 2 (Ryr2), in LV was lower in diabetic but not eplerenone- or balcinrenone-treated diabetic mice. Although balcinrenone and eplerenone similarly modified cardiac changes, potassium excretion was greater with balcinrenone, consistent with a reduced risk of hyperkalemia with the non-steroidal MR modulator.
Kanki et al. (Fri,) reported a other. Balcinrenone maintained normal urine potassium excretion in diabetic mice versus reduced excretion with eplerenone, suggesting lower hyperkalemia risk.