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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Meta-Analysis

A Systematic Review and Meta-analysis of Efficacy and Safety of Calcimimetic Agents in the Treatment of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

Author(s): Yiping Liu, Qian Yang, Guangyong Chen and Tianbiao Zhou*

Volume 28, Issue 40, 2022

Published on: 10 November, 2022

Page: [3289 - 3304] Pages: 16

DOI: 10.2174/1381612829666221027110656

Price: $65

Abstract

Background: Some reports have pointed out that calcimimetics agents are effective in the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, but there is no detailed description of the advantages and disadvantages of calcimimetics agents of SHPT in CKD patients. We tried to pool the published data to verify the effectiveness of calcimimetics agents and to compare the advantages and disadvantages of cinacalcet compared with control in the treatment of SHPT in CKD patients.

Methods: We included eligible studies of published papers from January 1st, 2000 to December 31st, 2020 in Medline, Pubmed and Web of science databases, and the data were extracted for this meta-analysis.

Results: Twenty-seven studies were eligible, and all the included studies were randomized controlled trials (RCT) including patients treated with long-term dialysis. The results indicated that calcimimetic agents can reduce the parathyroid hormone (PTH, pg/ml) level (WMD = -178.22, 95% CI: -238.57, -117.86, P < 0.00001), calcium (Ca, mg/dl) level (WMD = -0.71, 95% CI: -0.86, -0.55, P < 0.00001), phosphorus (P, mg/dl) level (WMD = -0.32, 95% CI: -0.55, -0.08, P = 0.008), calcium-phosphorus product level (WMD = -7.73, 95% CI: -9.64, -5.82, P < 0.00001). Calcimimetic agents increased the bone alkaline phosphatase (BSAP, ng/ml) levels and rate of achieving target PTH, and reduced osteocalcin levels and the rate of parathyroidectomy. Calcimimetic agents increased the total adverse events’ rate, the rate of hypocalcemia and gastrointestinal side effects (nausea, vomiting, abdominal pain and diarrhea), but there was no significant difference in serious adverse events between the calcimimetic agent group and control group.

Conclusion: Calcimimetic agents can reduce the PTH level, Ca level, P level, calcium-phosphorus product level and do not increase serious adverse events.

« Previous Next »
[1]
Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: Pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol 2011; 6(4): 913-21.
[http://dx.doi.org/10.2215/CJN.06040710] [PMID: 21454719]
[2]
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease–mineral and bone disorder (CKD-MBD). Kidney Int Suppl 2017; 7(1): 1-59.
[http://dx.doi.org/10.1016/j.kisu.2017.04.001] [PMID: 30675420]
[3]
Leifheit-Nestler M, große Siemer R, Flasbart K, et al. Induction of cardiac fgf23/fgfr4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease. Nephrol Dial Transplant 2016; 31(7): 1088-99.
[http://dx.doi.org/10.1093/ndt/gfv421] [PMID: 26681731]
[4]
Bouma-de Krijger A, Bots ML, Vervloet MG, et al. Time-averaged level of fibroblast growth factor-23 and clinical events in chronic kidney disease. Nephrol Dial Transplant 2014; 29(1): 88-97.
[http://dx.doi.org/10.1093/ndt/gft456] [PMID: 24215017]
[5]
Cernaro V, Santoro D, Lucisano S, Nicocia G, Lacquaniti A, Buemi M. The future of phosphate binders: A perspective on novel therapeutics. Expert Opin Investig Drugs 2014; 23(11): 1459-63.
[http://dx.doi.org/10.1517/13543784.2014.962652] [PMID: 25243756]
[6]
Goodman WG, Frazao JM, Goodkin DA, Turner SA, Liu W, Coburn JW. A calcimimetic agent lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism. Kidney Int 2000; 58(1): 436-45.
[http://dx.doi.org/10.1046/j.1523-1755.2000.00183.x] [PMID: 10886592]
[7]
Goodman WG, Hladik GA, Turner SA, et al. The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol 2002; 13(4): 1017-24.
[http://dx.doi.org/10.1681/ASN.V1341017] [PMID: 11912261]
[8]
Lindberg JS, Moe SM, Goodman WG, et al. The calcimimetic AMG 073 reduces parathyroid hormone and calcium X phosphorus in secondary hyperparathyroidism. Kidney Int 2003; 63(1): 248-54.
[http://dx.doi.org/10.1046/j.1523-1755.2003.00720.x] [PMID: 12472790]
[9]
Quarles LD, Sherrard DJ, Adler S, et al. The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. J Am Soc Nephrol 2003; 14(3): 575-83.
[http://dx.doi.org/10.1097/01.ASN.0000050224.03126.AD] [PMID: 12595492]
[10]
Block GA, Martin KJ, de Francisco ALM, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 2004; 350(15): 1516-25.
[http://dx.doi.org/10.1056/NEJMoa031633] [PMID: 15071126]
[11]
Harris RZ, Padhi D, Marbury TC, Noveck RJ, Salfi M, Sullivan JT. Pharmacokinetics, pharmacodynamics, and safety of cinacalcet hydrochloride in hemodialysis patients at doses up to 200 mg once daily. Am J Kidney Dis 2004; 44(6): 1070-6.
[http://dx.doi.org/10.1053/j.ajkd.2004.08.029] [PMID: 15558528]
[12]
Charytan C, Coburn JW, Chonchol M, et al. Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with ckd not receiving dialysis. Am J Kidney Dis 2005; 46(1): 58-67.
[http://dx.doi.org/10.1053/j.ajkd.2005.04.013] [PMID: 15983958]
[13]
Lindberg JS, Culleton B, Wong G, et al. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: A randomized, double-blind, multicenter study. J Am Soc Nephrol 2005; 16(3): 800-7.
[http://dx.doi.org/10.1681/ASN.2004060512] [PMID: 15689407]
[14]
Fishbane S, Shapiro WB, Corry DB, et al. Cinacalcet HCl and concurrent low-dose vitamin D improves treatment of secondary hyperparathyroidism in dialysis patients compared with vitamin D alone: The achieve study results. Clin J Am Soc Nephrol 2008; 3(6): 1718-25.
[http://dx.doi.org/10.2215/CJN.01040308] [PMID: 18945995]
[15]
Akiba T, Akizawa T, Tsukamoto Y, Uchida E, Iwasaki M, Koshikawa S. Dose determination of cinacalcet hydrochloride in japanese hemodialysis patients with secondary hyperparathyroidism. Ther Apher Dial 2008; 12(2): 117-25.
[http://dx.doi.org/10.1111/j.1744-9987.2008.00556.x] [PMID: 18387159]
[16]
Fukagawa M, Yumita S, Akizawa T, et al. Cinacalcet (KRN1493) effectively decreases the serum intact pth level with favourable control of the serum phosphorus and calcium levels in japanese dialysis patients. Nephrol Dial Transplant 2007; 23(1): 328-35.
[http://dx.doi.org/10.1093/ndt/gfm534] [PMID: 17717030]
[17]
Messa P, Macário F, Yaqoob M, et al. The OPTIMA study: Assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperparathyroidism. Clin J Am Soc Nephrol 2008; 3(1): 36-45.
[http://dx.doi.org/10.2215/CJN.03591006] [PMID: 18178780]
[18]
Chonchol M, Locatelli F, Abboud HE, et al. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCL in participants with ckd not receiving dialysis. Am J Kidney Dis 2009; 53(2): 197-207.
[http://dx.doi.org/10.1053/j.ajkd.2008.09.021] [PMID: 19110359]
[19]
Raggi P, Chertow GM, Torres PU, et al. The Advance study: A randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant 2011; 26(4): 1327-39.
[http://dx.doi.org/10.1093/ndt/gfq725] [PMID: 21148030]
[20]
El-Shafey EM, Alsahow AE, Alsaran K, Sabry AA, Atia M. Cinacalcet hydrochloride therapy for secondary hyperparathyroidism in hemodialysis patients. Ther Apher Dial 2011; 15(6): 547-55.
[http://dx.doi.org/10.1111/j.1744-9987.2011.00994.x] [PMID: 22107691]
[21]
Chertow GM, Block GA, Correa-Rotter R, et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med 2012; 367(26): 2482-94.
[http://dx.doi.org/10.1056/NEJMoa1205624] [PMID: 23121374]
[22]
Ketteler M, Martin KJ, Wolf M, et al. Paricalcitol versus cinacalcet plus low-dose vitamin d therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: Results of the Impact SHPT study. Nephrol Dial Transplant 2012; 27(8): 3270-8.
[http://dx.doi.org/10.1093/ndt/gfs018] [PMID: 22387567]
[23]
Kim HJ, Kim H, Shin N, et al. Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: A randomized controlled study. BMC Nephrol 2013; 14(1): 112.
[http://dx.doi.org/10.1186/1471-2369-14-112] [PMID: 23705925]
[24]
Ureña-Torres P, Bridges I, Christiano C, et al. Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism. Nephrol Dial Transplant 2013; 28(5): 1241-54.
[http://dx.doi.org/10.1093/ndt/gfs568] [PMID: 23328710]
[25]
Bell G, Huang S, Martin KJ, Block GA. A randomized, double-blind, phase 2 study evaluating the safety and efficacy of AMG 416 for the treatment of secondary hyperparathyroidism in hemodialysis patients. Curr Med Res Opin 2015; 31(5): 943-52.
[http://dx.doi.org/10.1185/03007995.2015.1031731] [PMID: 25786369]
[26]
Mei C, Chen N, Ding X, et al. Efficacy and safety of cinacalcet on secondary hyperparathyroidism in chinese chronic kidney disease patients receiving hemodialysis. Hemodial Int 2016; 20(4): 589-600.
[http://dx.doi.org/10.1111/hdi.12410] [PMID: 26940692]
[27]
Yokoyama K, Fukagawa M, Shigematsu T, et al. A single and multiple dose, multicenter study of etelcalcetide in japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int Rep 2017; 2(4): 634-44.
[http://dx.doi.org/10.1016/j.ekir.2017.01.016] [PMID: 29142982]
[28]
Block GA, Bushinsky DA, Cunningham J, et al. Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism. JAMA 2017; 317(2): 146-55.
[http://dx.doi.org/10.1001/jama.2016.19456] [PMID: 28097355]
[29]
Fukagawa M, Yokoyama K, Shigematsu T, et al. A phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese haemodialysis patients. Nephrol Dial Transplant 2017; 32(10): gfw408.
[http://dx.doi.org/10.1093/ndt/gfw408] [PMID: 28057872]
[30]
Akizawa T, Shimazaki R, Fukagawa M. Phase 2b study of evocalcet (KHK7580), a novel calcimimetic, in japanese patients with secondary hyperparathyroidism undergoing hemodialysis: A randomized, double-blind, placebo-controlled, dose-finding study. PLoS One 2018; 13(10): e0204896.
[http://dx.doi.org/10.1371/journal.pone.0204896] [PMID: 30379826]
[31]
Fukagawa M, Shimazaki R, Akizawa T. Head-to-head comparison of the new calcimimetic agent evocalcet with cinacalcet in japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int 2018; 94(4): 818-25.
[http://dx.doi.org/10.1016/j.kint.2018.05.013] [PMID: 30049473]
[32]
Susantitaphong P, Vadcharavivad S, Susomboon T, et al. The effectiveness of cinacalcet: A randomized, open label study in chronic hemodialysis patients with severe secondary hyperparathyroidism. Ren Fail 2019; 41(1): 326-33.
[http://dx.doi.org/10.1080/0886022X.2018.1562356] [PMID: 31014177]
[33]
Sternlicht H, Glezerman IG. Hypercalcemia of malignancy and new treatment options. Ther Clin Risk Manag 2015; 11: 1779-88.
[PMID: 26675713]
[34]
Bushinsky DA, Chertow GM, Cheng S, et al. One-year safety and efficacy of intravenous etelcalcetide in patients on hemodialysis with secondary hyperparathyroidism. Nephrol Dial Transplant 2020; 35(10): 1769-78.
[http://dx.doi.org/10.1093/ndt/gfz039] [PMID: 30859218]
[35]
Sun Y, Tian B, Sheng Z, Wan P, Xu T, Yao L. Efficacy and safety of cinacalcet compared with other treatments for secondary hyperparathyroidism in patients with chronic kidney disease or end-stage renal disease: A meta-analysis. BMC Nephrol 2020; 21(1): 316.
[http://dx.doi.org/10.1186/s12882-019-1639-9] [PMID: 32736534]
[36]
Lozano-Ortega G, Waser N, Bensink ME, et al. Effects of calcimimetics on long-term outcomes in dialysis patients: Literature review and bayesian meta-analysis. J Comp Eff Res 2018; 7(7): 693-707.
[http://dx.doi.org/10.2217/cer-2018-0015] [PMID: 29762046]
[37]
Palmer SC, Mavridis D, Johnson DW, Tonelli M, Ruospo M, Strippoli GFM. Comparative effectiveness of calcimimetic agents for secondary hyperparathyroidism in adults: A systematic review and network meta-analysis. Am J Kidney Dis 2020; 76(3): 321-30.
[http://dx.doi.org/10.1053/j.ajkd.2020.02.439] [PMID: 32475604]

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