Cinacalcet Improves Endothelial Dysfunction and Cardiac Hypertrophy in Patients on Hemodialysis with Secondary Hyperparathyroidism

Background: Secondary hyperparathyroidism (SHPT) in patients on hemodialysis is strongly associated with cardio-vascular morbidity and mortality. Treatment of SHPT with cinacalcet decreases circulating parathyroid hormone (PTH) concentrations and lowers serum calcium and phosphorus concentrations. Therefore, we investigated the cardiovascular effects of cinacalcet in hemodialysis patients with SHPT. Methods: We studied 12 hemodialysis patients with SPHT [serum intact PTH (iPTH) >300 pg/ml]. The study consisted of three phases: an initial run-in period of 16 weeks, including a wash-out period of 4 weeks (pretreatment), a cinacalcet treatment period of 20 weeks (treatment), and 20-week follow-up after suspension of cinacalcet treatment (posttreatment). In this study, vitamin D sterols were not prescribed to all the study subjects for at least 1 year during the pretreatment period. Results: Cinacalcet significantly decreased serum iPTH (pretreatment vs. treatment; 628.2 ± 250.8 vs. 251.7 ± 237.4 pg/ml, p < 0.01), calcium, phosphorus, and calcium × phosphorus product (p < 0.01), all of which returned to baseline levels after treatment. There was no change in C-reactive protein during the study period. There was significantly improvement in brachial flow-mediated dilatation (p < 0.01) and enhanced cardio-ankle vascular index (p < 0.01) with cinacalcet treatment. Moreover, cinacalcet significantly improved diastolic function (E/e' ratio, p < 0.05) and the left ventricular mass index (p < 0.05). Cinacalcet also increased serum NO x (p < 0.05) and decreased serum isoprostane (p < 0.05) and soluble intercellular adhesion molecule-1 concentrations (p < 0.05). All of these biochemical parameters returned to their pretreatment concentrations after withdrawal of cinacalcet. Conclusions: Cinacalcet hydrochloride without vitamin D might ameliorate endothelial dysfunction, diastolic dysfunction, and cardiac hypertrophy by decreasing oxidative stress and increasing the serum nitric oxide production in hemodialysis patients with SHPT.