The Role of the Old and the New Calcimimetic Agents in Chronic Kidney Disease-Mineral and Bone Disorder

Secondary hyperparathyroidism (SHPT) is associated with increased bone turnover, risk of fractures, vascular calcifications, cardiovascular and all-cause mortality. The classical treatment for SHPT includes active vitamin D compounds and phosphate binders. However, achieving the optimal laboratory targets is often difficult because vitamin D sterols suppress PTH secretion, but also promote calcium and phosphate intestinal absorption. Calcimimetics increase the sensitivity of calcium sensing receptor so that even with lower levels of extracellular calcium a signal can still exist, leading to the decrease of the set-point for systemic calcium homeostasis. This enables a decrease in plasma PTH levels, and consequently of calcium levels. Cinacalcet was the first calcimimetic approved for clinical use. After more than 15 years from its approval, cinacalcet demonstrated that effectively reduces PTH and improves biochemical control of mineral and bone disorders in chronic kidney patients. Three randomized controlled trials analyzed cinacalcet treatment effects on hard clinical outcomes such as vascular calcification, bone histology and cardiovascular mortality and morbidity. However, a final conclusion on the effect of cinacalcet on hard outcomes remains elusive. Etelcalcetide is a new second generation intra-venously administered calcimimetic agent with a pharmacokinetic profile that allows thrice-weekly dosing at the time of hemodialysis. It was recently approved in Europe and is regarded as a second opportunity to improve outcomes optimizing the treatment for SHPT. Evocalcet is the newly developed oral calcimimetic agent with less gastrointestinal adverse effects than cinacalcet and may be an alternative option for the treatment of secondary hyperparathyroidism in dialysis patients. This chapter summarizes the impact of cinacalcet in biochemical and relevant clinical outcomes, discusses the possible implications of etelcalcetide in the quest for improving outcomes and review the available data of the new oral calcimimetic evocalcet.