Calcimimetics such as etelcalcetide (ET) are used to manage secondary hyperparathyroidism patients with chronic kidney disease (CKD) on dialysis. While their cardiovascular benefits—including left ventricular hypertrophy (LVH) suppression—are recognized, the underlying mechanisms remain unclear. This study investigated how ET suppresses LVH using rat models.

LVH was induced via transverse aortic coarctation, and CKD by 5/6 nephrectomy. Rats were assigned to the sham, CKD, LVH, or CKD/LVH groups, with each pathological group further divided into vehicle- or ET-treated subgroups. After eight weeks of treatment, echocardiography, histological, biochemical, and molecular analyses were conducted.

ET reduced serum parathyroid hormone and fibroblast growth factor 23 (FGF23) levels in the CKD and CKD/LVH groups but not in the LVH group, where these levels were not increased. ET did not affect serum calcium, phosphorus, or vitamin D levels in the LVH and CKD/LVH groups. Nonetheless, ET suppressed cardiac hypertrophy and cardiomyocyte enlargement in the LVH and CKD/LVH groups despite no changes in systemic mineral metabolism parameters. Mechanistically, ET attenuated cardiac hypertrophy, serum aldosterone levels, and cardiac renin-angiotensin-aldosterone system (RAAS) components in the LVH and CKD/LVH groups. Cardiac FGF23 expression, elevated in the LVH and CKD/LVH groups, was also decreased by ET. The calcineurin/nuclear factor of the activated T-cell signaling pathway was unaffected.

ET effectively suppressed LVH in the LVH and CKD/LVH groups. These findings suggest that ET’s cardioprotective effects are mediated via the modulation of the RAAS and cardiac FGF23 expression rather than solely through the correction of CKD-mineral bone disorder abnormalities.