clinical value of Serum iPTH , ALP and serum markers levels in patients with secondary hyperparathyroidism receiving paricalcitol combined with cinacalcet
clinical value of Serum iPTH and ALP levels
Abstract
Objective: The objective of this research is to investigate the impact of combining paricalcitol with cinacalcet on the concentrations of intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) in patients with secondary hyperparathyroidism who are undergoing maintenance hemodialysis (MHD). Methods: A retrospective review was performed on the clinical records of 129 individuals diagnosed with chronic kidney disease and secondary hyperparathyroidism who underwent maintenance hemodialysis in the hemodialysis unit from June to December 2022. The patients were divided into three cohorts according to their treatment approach: Group A (paricalcitol treatment; 43 cases), Group B (cinacalcet treatment), and Group C (combined paricalcitol and cinacalcet treatment). Hemoglobin (Hb), serum albumin (Alb), calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), serum creatinine (Scr), and blood urea nitrogen (BUN) levels were assessed upon admission and at subsequent intervals of 1 day, 3 months, and 6 months for comparative evaluation across the three cohorts. Results: At 1 day post-hospitalization, the levels of hemoglobin (Hb) and serum albumin (Alb) in all three groups surpassed those in groups A and B (P＞0.05). Analysis of variance revealed significant differences in Ftime, Fgroup and F interaction (P＜0.05). Figure 2 (A, B) illustrates the comparison of calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) levels among the three cohorts. No statistically significant variances were detected in Ca, P, and iPTH levels across the three groups within 24 hours of admission (P＞0.05).Following 3 and 6 months of treatment, levels of Ca, P, and iPTH decreased across all groups compared to baseline (day 1), with Group C displaying the lowest levels relative to Groups A and B (P＜0.05). Significance was observed in Ftime, Fgroup and F interaction via analysis of variance (P＜0.05). Figure 4 (A-C) illustrates the comparison of alkaline phosphatase (ALP), serum creatinine (Scr), and blood urea nitrogen (BUN) levels among the three groups.No significant differences were found in ALP, Scr, and BUN levels among the three groups at 1 day post-admission (P＞0.05). Nevertheless, following 3 and 6 months of treatment, there was a decline in ALP, Scr, and BUN levels across all groups relative to those at day 1, with Group C demonstrating lower levels (P＜0.05).Repeated analysis of variance indicated significant differences in Ftime, Fgroup and F interaction (P＜0.05). Conclusion: The efficacy of paricalcitol combined with cinacalcet has been demonstrated in reducing levels of Hb, Alb, as well as Ca, P, and iPTH among individuals undergoing maintenance hemodialysis for secondary hyperparathyroidism.
References
Bargagli, M., Arena, M., Naticchia, A., Gambaro, G., Mazzaferro, S., Fuster, D. and Ferraro, P.M. The Role of Diet in Bone and Mineral Metabolism and Secondary Hyperparathyroidism. Nutrients. (2021). 13(7). https://doi.org/10.3390/nu13072328
Bover, J., Arana, C., Ureña, P., Torres, A., Martín-Malo, A., Fayos, L., Coll, V., Lloret, M.J., Ochoa, J., Almadén, Y., Guirado, L. and Rodríguez, M. Hyporesponsiveness or resistance to the action of parathyroid hormone in chronic kidney disease. Nefrologia (Engl Ed). (2021). 41(5): 514-528. https://doi.org/10.1016/j.nefroe.2021.11.014
Chang, G.H., Chou, F.F., Tsai, M.S., Tsai, Y.T., Yang, M.Y., Huang, E.I., Su, H.C. and Hsu, C.M. Real-world evidence and optimization of vocal dysfunction in end-stage renal disease patients with secondary hyperparathyroidism. Sci Rep. (2021). 11(1): 653. https://doi.org/10.1038/s41598-020-79810-0
Costa, T., Lauar, J.C., Innecchi, M., Coelho, V.A., Moysés, R. and Elias, R.M. Hyperuricemia is associated with secondary hyperparathyroidism in patients with chronic kidney disease. Int Urol Nephrol. (2022). 54(9): 2255-2261. https://doi.org/10.1007/s11255-022-03116-5
Dream, S., Kuo, L.E., Kuo, J.H., Sprague, S.M., Nwariaku, F.E., Wolf, M., Olson, J.A. Jr, Moe, S.M., Lindeman, B. and Chen, H. The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Secondary and Tertiary Renal Hyperparathyroidism. Ann Surg. (2022). 276(3): e141-e176. https://doi.org/10.1097/SLA.0000000000005522
Faye, M., Keita, N., Lemrabott, A.T., Algouzmari, I., Faye, M., Mbengue, M., Diagne, S., Ba, B., Dieng, A., Ba, M.A. and Ka, E. Surgical management of secondary hyperparathyroidism in dialysis patients in Senegal. Saudi J Kidney Dis Transpl. (2021). 32(5): 1424-1430. https://doi.org/10.4103/1319-2442.344763
Fukazawa-Shinotsuka, M., Saito, T., Abe, M., Iida, S., Wang, I.T., Terao, K., Chen, H.H. and Liu, M.C. Maxacalcitol Pharmacokinetic-Pharmacodynamic Modeling and Simulation for Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis. Drug Res (Stuttg). (2022). 72(1): 23-33. https://doi.org/10.1055/a-1581-7609
Gong, W., Xie, Y., Lin, Y., Meng, Z. and Wang, Y. [Risk factors affecting graft survival after parathyroidectomy and parathyroid autotransplantation in patients on maintenance hemodialysis]. Nan Fang Yi Ke Da Xue Xue Bao. (2021). 41(6): 947-952. https://doi.org/10.12122/j.issn.1673-4254.2021.06.20
Gong, X., Wang, Y.A., Li, C., Liao, X., Li, S., Yang, L., Jiang, X., Sun, Y., Xu, J., Tong, Z. and Lu, Y. Effect of total parathyroidectomy in patients with secondary hyperparathyroidism: a retrospective study. Int Urol Nephrol. (2023). 55(5): 1239-1245. https://doi.org/10.1007/s11255-022-03401-3
Goodman, W.G. and Quarles, L.D. Development and progression of secondary hyperparathyroidism in chronic kidney disease: lessons from molecular genetics. Kidney Int. (2008). 74(3): 276-288. https://doi.org/10.1038/sj.ki.5002287
Hasegawa, T., Tokunaga, S., Yamamoto, T., Sakai, M., Hongo, H., Kawata, T. and Amizuka, N. Evocalcet Rescues Secondary Hyperparathyroidism-driven Cortical Porosity in CKD Male Rats. Endocrinology. (2023). 164(4). https://doi.org/10.1210/endocr/bqad022
Hu, L., Napoletano, A., Provenzano, M., Garofalo, C., Bini, C., Comai, G. and La Manna, G. Mineral Bone Disorders in Kidney Disease Patients: The Ever-Current Topic. Int J Mol Sci. (2022). 23(20). https://doi.org/10.3390/ijms232012223
Isakova, T., Nickolas, T.L., Denburg, M., Yarlagadda, S., Weiner, D.E., Gutiérrez, O.M., Bansal, V., Rosas, S.E., Nigwekar, S., Yee, J. and Kramer, H. KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Am J Kidney Dis. (2017). 70(6): 737-751. https://doi.org/10.1053/j.ajkd.2017.07.019
Karaboyas, A., Muenz, D., Fuller, D.S., Desai, P., Lin, T.C., Robinson, B.M., Rossetti, S. and Pisoni, R.L. Etelcalcetide Utilization, Dosing Titration, and Chronic Kidney Disease-Mineral and Bone Disease (CKD-MBD) Marker Responses in US Hemodialysis Patients. Am J Kidney Dis. (2022). 79(3): 362-373. https://doi.org/10.1053/j.ajkd.2021.05.020
Li, B., Chen, X., Hu, J., Ke, G., Jiang, N., Zhang, F., Lian, Z., Wen, S., Wu, Q., Xia, Y., Zhang, H., Kuang, S., Xu, L., Deng, C. and Liu, S. COMMD5 is involved in the mechanisms of hypotension after parathyroidectomy in patients receiving hemodialysis. Eur J Pharmacol. (2023). 944: 175596. https://doi.org/10.1016/j.ejphar.2023.175596
Li, P., Li, G., Liu, L., Huang, S., Li, J. and Wu, W. [Cultivation and characterization of primary human parathyroid cells from patients with severe secondary hyperparathyroidism]. Nan Fang Yi Ke Da Xue Xue Bao. (2022). 42(2): 238-243. https://doi.org/10.12122/j.issn.1673-4254.2022.02.10
Li, X., Ding, W. and Zhang, H. Cinacalcet use in secondary hyperparathyroidism: a machine learning-based systematic review. Front Endocrinol (Lausanne). (2023). 14: 1146955. https://doi.org/10.3389/fendo.2023.1146955
Li, X., Lu, Y., Zhang, L., Song, A., Zhang, H., Pang, B., Liu, J., Sun, X., Ji, H., Huang, L. and Yang, M. Primary and secondary hyperparathyroidism present different expressions of calcium-sensing receptor. BMC Surg. (2023). 23(1): 31. https://doi.org/10.1186/s12893-023-01928-5
Liu, Y., Yang, Q., Chen, G. and Zhou, T. 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. Curr Pharm Des. (2022). 28(40): 3289-3304. https://doi.org/10.2174/1381612829666221027110656
Massimetti, C., Imperato, G. and Feriozzi, S. [Cholecalciferol supplementation improves secondary hyperparathyroidism control in renal transplant recipient]. G Ital Nefrol. (2020). 37(4).
Miedziaszczyk, M., Idasiak-Piechocka, I., Wiśniewski, O.W. and Lacka, K. A systematic review of the pharmacotherapy of secondary hyperparathyroidism (SHPT) in grades 3-5 Chronic Kidney Disease (CKD). Eur Rev Med Pharmacol Sci. (2022). 26(1): 232-239. https://doi.org/10.26355/eurrev_202201_27773
Neagoe, R.M., Sala, D.T., Voidazan, S., Arpad, T., Cosma, G.M., Mureșan, S., Suciu, B., Melano, M.I. and Mureșan, M. A comparative analysis of three types of parathyroidectomies in renal hyperparathyroidism Single centre prospective cohort of 77 patients. Ann Ital Chir. (2021). 92: 6-12.
Ni, Z., Liang, X., Wu, C.C., Jin, K., Kim, Y.L., Lu, K.C., Chan, T.M., Fukagawa, M., Kinoshita, J., Nagai, C., Kojima, M., Yu, X. and Orchestra Study Group. Comparison of the Oral Calcimimetics Evocalcet and Cinacalcet in East Asian Patients on Hemodialysis with Secondary Hyperparathyroidism. Kidney Int Rep. (2023). 8(11): 2294-2306. https://doi.org/10.1016/j.ekir.2023.08.034
Pereira, L., Meng, C., Amoedo, M., Mendes, M., Marques, M., Frazão, J. and Weigert, A. Etelcalcetide controls secondary hyperparathyroidism and raises sclerostin levels in hemodialysis patients previously uncontrolled with cinacalcet. Nefrologia (Engl Ed). (2023). 43(2): 197-203. https://doi.org/10.1016/j.nefroe.2022.11.014
Petranović Ovčariček, P., Giovanella, L., Hindie, E., Huellner, M.W., Talbot, J.N. and Verburg, F.A. An essential practice summary of the new EANM guidelines for parathyroid imaging. Q J Nucl Med Mol Imaging. (2022). 66(2): 93-103. https://doi.org/10.23736/S1824-4785.22.03427-6
Reichel, H., Seibert, E., Tillmann, F.P., Barck, I., Grava, A., Schneider, K.M. and Meise, D. Economic burden of secondary hyperparathyroidism in Germany: a matched comparison. Int Urol Nephrol. (2023). 55(5): 1291-1300. https://doi.org/10.1007/s11255-022-03425-9
Sakai, M., Tokunaga, S., Kawai, M., Murai, M., Kobayashi, M., Kitayama, T., Saeki, S. and Kawata, T. Evocalcet prevents ectopic calcification and parathyroid hyperplasia in rats with secondary hyperparathyroidism. PLoS One. (2020). 15(4): e0232428. https://doi.org/10.1371/journal.pone.0232428
Sheerah, A.A., Al-Ahmed, R.A., El-Desoky, S.M., Alhasan, K.A., Albanna, A.S., Shalaby, M.A. and Kari, J.A. Cinacalcet for Severe Secondary Hyperparathyroidism in Children with End-stage Kidney Disease. Saudi J Kidney Dis Transpl. (2021). 32(6): 1628-1636. https://doi.org/10.4103/1319-2442.352423
Takeuchi, M., Takahashi, T., Shodo, R., Ota, H., Ueki, Y., Yamazaki, K. and Horii, A. Comparison of Autofluorescence With Near-Infrared Fluorescence Imaging Between Primary and Secondary Hyperparathyroidism. Laryngoscope. (2021). 131(6): E2097-E2104. https://doi.org/10.1002/lary.29310
Tokumoto M, Tokunaga S, Asada S, et al. Predictive factors requiring high-dose evocalcet in hemodialysis patients with secondary hyperparathyroidism. PLoS One. 2022. 17(12): e0279078.
Wang, A.Y., Tang, T.K., Yau, Y.Y. and Lo, W.K. Impact of Parathyroidectomy Versus Oral Cinacalcet on Bone Mineral Density in Patients on Peritoneal Dialysis With Advanced Secondary Hyperparathyroidism: The PROCEED Pilot Randomized Trial. Am J Kidney Dis. (2023) . https://doi.org/10.1053/j.ajkd.2023.10.007
Wang, N., Xie, Y. and Jiang, G. Efficacy and safety of intravenous paricalcitol treatment in Chinese hemodialysis patients: a real-world database analysis. Ann Palliat Med. (2022). 11(1): 225-239. https://doi.org/10.21037/apm-21-3966
Warady, B.A., Ng, E., Bloss, L., Mo, M., Schaefer, F. and Bacchetta, J. Cinacalcet studies in pediatric subjects with secondary hyperparathyroidism receiving dialysis. Pediatr Nephrol. (2020). 35(9): 1679-1697. https://doi.org/10.1007/s00467-020-04516-4
Wen, P., Xu, L., Zhao, S., Gan, W., Hou, D., Zhang, L., Cao, J., Xiong, M., Jiang, L. and Yang, J. Risk Factors for Severe Hypocalcemia in Patients with Secondary Hyperparathyroidism after Total Parathyroidectomy. Int J Endocrinol. (2021). 2021: 6613659. https://doi.org/10.1155/2021/6613659
Xu, W., Gong, L., Lu, J. and Tang, W. Paricalcitol vs. cinacalcet for secondary hyperparathyroidism in chronic kidney disease: A meta-analysis. Exp Ther Med. (2020). 20(4): 3237-3243. https://doi.org/10.3892/etm.2020.9044
Yokoyama, K., Fukagawa, M., Shigematsu, T., Akiba, T., Yoshikawa, K., Tsuchiya, A., Kuwabara, M. and Akizawa, T. Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52 weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan. Clin Exp Nephrol. (2021). 25(1): 66-79. https://doi.org/10.1007/s10157-020-01936-2
Zhang, L.X., Zhang, B., Liu, X.Y., Wang, Z.M., Qi, P., Zhang, T.Y. and Zhang, Q. Advances in the treatment of secondary and tertiary hyperparathyroidism. Front Endocrinol (Lausanne). (2022). 13: 1059828. https://doi.org/10.3389/fendo.2022.1059828
Copyright (c) 2025 Xiaozhen Lu
This work is licensed under a Creative Commons Attribution 4.0 International License.
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.