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

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Parathyroid Glands in Chronic Kidney Disease

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Abstract

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.

In preparation of this book chapter, we used previously published material, with permission (Licence number 4463751218679)—Review Paper “Old and new calcimimetics for treatment of secondary hyperparathyroidism: impact on biochemical and relevant clinical outcomes”; authors Luciano Pereira, Catarina Meng, Daniela Marques and João M. Frazão; Clinical Kidney Journal, 2018, vol 11, no.1, 80–88.

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Authors and Affiliations

  1. Institute of Investigation and Innovation in Health, University of Porto, Porto, Portugal

    Luciano Pereira & João M. Frazão

  2. INEB – National Institute of Biomedical Engineering, University of Porto, Porto, Portugal

    Luciano Pereira & João M. Frazão

  3. Department of Nephrology, São João Hospital Center, Porto, Portugal

    Luciano Pereira & João M. Frazão

  4. DaVita Kidney Care, Amadora, Portugal

    João M. Frazão

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  1. Luciano Pereira
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Correspondence to João M. Frazão .

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Editors and Affiliations

  1. Internal Medicine - Nephrology, Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania

    Adrian Covic

  2. Renal Unit, Guy's and St Thomas' NHS Foundation Hospital, London, UK

    David Goldsmith

  3. Nephrology-Dialysis Service, AURA Nord Saint Ouen, Saint Ouen, France

    Pablo A. Ureña Torres

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Luciano Pereira received speaker honoraria and travel grant from Amgen. João Frazão received consulting, speaker and travel honoraria from Amgen.

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Pereira, L., Frazão, J.M. (2020). The Role of the Old and the New Calcimimetic Agents in Chronic Kidney Disease-Mineral and Bone Disorder. In: Covic, A., Goldsmith, D., Ureña Torres, P. (eds) Parathyroid Glands in Chronic Kidney Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-43769-5_11

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