CONTROL OF SECONDARY HYPERPARATIREOSIS BY INTRAVENOUS INTRODUCTION OF PARSABIV IN PATIENTS WITH CHRONIC KIDNEY DISEASE V D STAGE IN HEMODIALYSIS
Keywords:chronic kidney disease, hemodialysis, etelcalcetide, parsabiv, cinacalcet, secondary hyperparathyroidism
Introduction. Secondary hyperparathyroidism (VGPT), a common complication of chronic kidney disease characterized by elevated serum parathyroid hormone (PTH). Parsabiv (etecalcetide) is an intravenous calcimimetic that increases the sensitivity of the calciumsensitive receptor to calcium and reduces the secretion of PTH.
Goal. Evaluation of VGPT control by intravenous administration of Parsabiv in patients with end-stage chronic kidney disease (CKD) treated with hemodialysis (HD) compared with cinacalcet for oral administration.
Materials and methods. A prospective observational study included 40 patients with VGPT treated with HD who had not previously received appropriate treatment (ie, never received calcimimetics before), patients who had previously received cinacalcet, and patients who continued to receive cinacalcet. The primary endpoint for efficacy was the number of patients with a PTH reduction of more than 30% compared to baseline at the efficacy stage (weeks 12-14) and whether Parsabiv was more effective in controlling VGPT than cinacalcet. Secondary endpoints were presented by some patients who achieved a reduction in PTH levels of more than 50% from baseline and a reduction in PTH and calcium levels during the evaluation period.
Results and discussion. The study included data from 40 patients obtained during a 14-week follow-up period. The mean age of 40 patients was 47.62 ± 12.97 years, 70% were male. The average duration of dialysis was 8.3 ± 2.34 years. The mean PTH concentration before the start of the study and for 12-14 weeks was 1137.34 ± 544.84 and 838.7 ± 458.8 pg / ml and 1010.6± 478.53 and 760.8 ± 373.86 pg / Jr. in the Parsabiva and cinacalcet groups, respectively. The mean total calcium remained within the normal range in the Parsabiva group and in the cinacalcet group, although the decrease in total calcium was higher in the Parsabiva group (2.23% vs. 5.15%), in all cases it was not accompanied by symptoms.
Conclusions. The results of our observational study are of clinical interest. They confirm that the use of Parsabiva is a new important treatment option for patients with VGPT. Parsabiv has been shown to be more effective in controlling VGPT in patients compared with cinacalcet. In addition, the use of Parsabiv helps to reduce the stress caused by the need to take a large number of drugs, typical of dialysis patients, and thus may contribute to better adherence to the recommended treatment regimen and eliminate the risk of persistent VGPT. It is also important that Parsabiv does not interact with isoenzymes of the cytochrome P450 system, that is, there are no interactions with other drugs received by dialysis patients.
Further studies are needed to assess the clinical consequences, as well as efficacy and safety with long-term use.
2. Сторожук О.Б., Луговський Е.В., Сторожук Л.О., Сторожук Б.Г., Селезньова І.Б. Вплив вторинного гіперпаратиреозу на деякі показники гемостазу у хворих хронічною хворобою нирок VД стадії. Вісник проблем біології і медицини. 2018. 2 (1): 201-204
3. Block, G.A.; Bushinsky, D.A.; Cunningham, J.; Drueke, T.B.; Ketteler, M.; Kewalramani, R., et al. Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism. JAMA. 2017;317(2):146-155.
4. Block, G.A.; Bushinsky, D.A.; Cheng, S.; Cunningham, J.; Dehmel, B.; Drueke, T.B., et al. Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis. With Secondary Hyperparathyroidism. JAMA 2017; 317(2),156–164.
5. David A. Bushinsky, Glenn M. Chertow, Sunfa Cheng, Hongjie Deng, Nelson Kopyt, Kevin J. Martin, et al. One-year safety and efficacy of intravenous etelcalcetide in patients on hemodialysis with secondary hyperparathyroidism. Nephrol Dial Transplant. 2020; 35(10): 1769-1778
6. Russo D., Tripepi R., Malberti F., Iorio D.B., Scognamiglio B., Lullo D.L., et al. Etelcalcetide in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism. Multicenter Studyin “Real Life”. J. Clin. Med. 2019, 8(7), 1066;
7. Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, et al. Executivesummary of the 2017 KDIGO chronic kidney disease-mineral and bone disorder (CKD-MBD) guideline update: what’s changed and why it matters. Kidney Int 2017;92:26–36.
8. Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, et al: Diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder: synopsis of the kidney disease: improving global outcomes 2017 clinical practice guideline update. Ann Intern Med 2018; 168: 422– 430.
9. Martin, K.J.; Pickthorn, K.; Huang, S.; Block, G.A.; Vick, A.; Mount, P.F.; Power, D.A.; Bell, G. AMG 416 (velcalcetide) is a novel peptide for the treatment of secondary hyperparathyroidism in a single-dose study in hemodialysis patients. Kidney Int. 2013, 85 (1): 191–197.
10. Subramanian, R.; Zhu, X.; Kerr, S.J.; Esmay, J.D.; Louie, S.W.; Edson, K.Z.; Walter, S.; Fitzsimmons, M.; Wagner, M.; Soto, M. Nonclinical Pharmacokinetics, Disposition, and Drug-Drug Interaction Potential of a Novel d-Amino Acid Peptide Agonist of the Calcium- Sensing Receptor AMG 416 (Etelcalcetide). Drug Metab. Dispos. 2016, 44 (8): 1319–1331