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Том 25 №2 2023 год - Нефрология и диализ

Вторичный гиперпаратиреоз. Специфика, сложности, особенности лечения. Обзор литературы. Часть I

Шабунин А.В. Шутов Е.В. Долидзе Д.Д. Захарова Е.В. Слепухова Д.В. Кованцев С.Д. Большаков С.А.

DOI: 10.28996/2618-9801-2023-2-222-231

Аннотация: В представленном обзоре литературы освещены современные представления о патогенезе и актуальные вопросы медикаментозного лечения вторичного гиперпаратиреоза у больных с хронической болезнью почек. Факторами развития и прогрессирования вторичного гиперпаратиреоза считают наличие гипокальциемии, гиперфосфатемии и низкий уровень кальцитриола. На первых этапах лечения вторичного гиперпаратиреоза используется консервативный подход, который направлен на коррекцию каждого из этих факторов. В обзоре обобщен опыт использования фосфат-связывающих препаратов, витамина Д и его аналогов и кальцимиметиков у данной категории больных. Рассмотрены механизмы действия этих препаратов и представлены схемы лечения для достижения удовлетворительного контроля минерально-костного обмена и снижения рисков развития и прогрессирования тяжелого гиперпаратиреоза.

Для цитирования: Шабунин А.В., Шутов Е.В., Долидзе Д.Д., Захарова Е.В., Слепухова Д.В., Кованцев С.Д., Большаков С.А. Вторичный гиперпаратиреоз. Специфика, сложности, особенности лечения. Обзор литературы. Часть I. Нефрология и диализ. 2023. 25(2):222-231. doi: 10.28996/2618-9801-2023-2-222-231

Весь текст

Ключевые слова: хроническая болезнь почек, гемодиализ, вторичный гиперпаратиреоз, патогенез, фосфат-связывающие препараты, витамин D, кальцимиметики, паратгормон, околощитовидные железы, chronic kidney disease, hemodialysis, secondary hyperparathyroidism, pathogenesis, phosphate binders, vitamin D, calcimimetics, PTH, parathyroid gland

Список литературы:

1. National Kidney Foundation K/DOQIK/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003. 42(4 Suppl 3): S1-S201. PMID: 14520607. doi: 10.1016/S0272-6386(03)00905-3
2. Ветчинникова О.Н. Гиперпаратиреоз при хронической болезни почек. Эффективная фармакотерапия. Журнал Урология и нефрология. 2013. (2):26-39.
3. Bureo J.C., Arévalo J.C., Antón J. et al. Prevalence of secondary hyperparathyroidism in patients with stage 3 and 4 chronic kidney disease seen in internal medicine. Endocrinol Nutr. 2015. 62:300-305. doi: 10.1016/j.endonu.2015.05.006
4. Levin A., Bakris G.L., Molitch M. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007. 71:31-38. doi: 10.1038/sj.ki.5002009
5. Ramos A.M., Albalate M., Vázquez S. et al. Hyperphosphatemia and hyperparathyroidism in incident chronic kidney disease patients. Kidney Int Suppl. 2008. (suppl): S88-S93. doi: 10.1038/ki.2008.543
6. Dialysis Outcomes Practice Patterns Study (DOPPS) practice monitor. Arbor Research Collective for Health. https://www.dopps.org/DPM.
7. Neves K.R., Graciolli F.G., dos Reis L.M. et al. Vascular calcification: Contribution of parathyroid hormone in renal failure. Kidney Int. 71: 1262-1270, 2007. doi: 10.1038/sj.ki.5002241
8. Block G.A., Klassen P.S., Lazarus J.M. et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004. 15:2208-2218, doi: 10.1097/01.ASN.0000133041.27682.A2
9. Бикбов Б.Т., Томилина Н.А. Состав больных и показатели качества лечения на заместительной терапии терминальной хронической почечной недостаточности в Российской Федерации в 1998-2013 гг. Нефрология и диализ. 2016. 18(2):98-164.
10. Cunningham J., Locatelli F., Rodriguez M.: Secondary hyperparathyroidism: Pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol. 2011. 6: 913-921. doi: 10.2215/CJN.06040710
11. Martin A., David V., Quarles L.D. Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev. 2012. 92(1):131-55. doi: 10.1152/physrev.00002.2011
12. Gogusev J., Duchambon P., Hory B. et al. Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int. 1997. 51(1):328-36. doi: 10.1038/ki.1997.41. PMID: 8995751
13. Rodriguez M., Nemeth E., Martin D. The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism. Am J Physiol Renal Physiol. 2005. 288(2):F253-64. doi: 10.1152/ajprenal.00302.2004.
14. Canalejo R., Canalejo A., Martinez-Moreno J.M. et al. FGF23 fails to inhibit uremic parathyroid glands. J Am Soc Nephrol. 2010. 21(7):1125-35. doi: 10.1681/ASN.2009040427
15. Fan Y., Liu W., Bi R. et al. Interrelated role of Klotho and calcium-sensing receptor in parathyroid hormone synthesis and parathyroid hyperplasia. Proc Natl Acad Sci U S A. 2018. 115(16):E3749-E3758. doi: 10.1073/pnas.1717754115
16. Centeno P.P., Herberger A., Mun H.-C. et al. Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. Nat. Commun. 2019. 10:4693. doi: 10.1038/s41467-019-12399-9
17. Slatopolsky E., Brown A., Dusso A. Pathogenesis of secondary hyperparathyroidism. Kidney Int Suppl. 1999. 73:S14-9. doi: 10.1046/j.1523-1755.1999.07304.x.
18. Slatopolsky E., Brown A., Dusso A. Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis. 2001. 37 (1 Suppl 2):S54-7. doi: 10.1053/ajkd.2001.20740
19. Martin K.J., Floege J., Ketteler M. Bone and Mineral Disorders in Chronic Kidney Disease. In: Feehally J., editor. Comprehensive Clinical Nephrology. 6th ed. Springer; Berlin/Heidelberg, Germany: 2019.
20. Asci G., Ok E., Savas R. et al. The link between bone and coronary calcifications in CKD-5 patients on haemodialysis. Nephrol Dial Transpl. 2011. 26:1010-1015. doi: 10.1093/ndt/gfq491
21. Fang Y., Ginsberg C., Seifert M. et al. CKD-induced wingless/integration1 inhibitors and phosphorus cause the CKD-mineral and bone disorder. J Am SocNephrol 2014. 25:1760-1773. doi: 10.1681/ASN.2013080818
22. Pasieka J.L., Parsons L.L. A prospective surgical outcome study assessing the impact of parathyroidectomy on symptoms in patients with secondary and tertiary hyperparathyroidism. Surgery. 2000. 128(4):531-9. doi: 10.1067/msy.2000.108117
23. Rodríguez-Ortiz M.E., Pendón-Ruiz de Mier M.V., Rodríguez M. Parathyroidectomy in dialysis patients: Indications, methods, and consequences. Semin Dial. 2019. 32(5):444-451. doi: 10.1111/sdi.12772
24. Kraus M.A., Kalra P.A., Hunter J. et al. The prevalence of vascular calcification in patients with end-stage renal disease on hemodialysis: a cross-sectional observational study. Ther Adv Chronic Dis. 2015. 6:84-96. doi: 10.1177/2040622315578654
25. Giachelli C.M. The emerging role of phosphate in vascular calcification. Kidney Int. 2009. 75:890-897. doi: 10.1038/ki.2008.644
26. Jono S., McKee M.D., Murry C.E. et al. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res. 2000. 87:E10- E17. doi: 10.1161/01.res.87.7.e10
27. Isakova T., Nickolas T.L., Denburg M. et al. 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. doi: 10.1053/j.ajkd.2017.07.019
28. Schmid H., Hartmann B., Schiffl H. Adherence to prescribed oral medication in adult patients undergoing chronic hemodialysis: a critical review of the literature. Eur J Med Res. 2009. 14(5):185-190. doi: 10.1186/2047-783x-14-5-185
29. Karamanidou C., Clatworthy J., Weinman J. et al. A systematic review of the prevalence and determinants of nonadherence to phosphate binding medication in patients with end-stage renal disease. BMC Nephrol. 2008. 9:2. doi: 10.1186/1471-2369-9-2
30. Covic A., Rastogi A. Hyperphosphatemia in patients with ESRD: assessing the current evidence linking outcomes with treatment adherence. BMC Nephrol. 2013. 14:153. doi: 10.1186/1471-2369-14-153
31. Ghimire S., Castelino R.L., Lioufas N.M. et al. Nonadherence to Medication Therapy in Haemodialysis Patients: A Systematic Review. PLoS One. 2015. 10(12):e0144119. doi: 10.1371/journal.pone.0144119
32. Lynch K.E., Lynch R., Curhan G.C., Brunelli S.M. Prescribed dietary phosphate restriction and survival among hemodialysis patients. Clin J Am Soc Nephrol. 2011. 6(3):620-9. doi: 10.2215/CJN.04620510
33. Kalantar-Zadeh K. Patient education for phosphorus management in chronic kidney disease. Patient Prefer Adherence. 2013. 7:379-90. doi: 10.2147/PPA.S43486
34. Waheed A.A., Pedraza F., Lenz O., Isakova T. Phosphate control in end-stage renal disease: barriers and opportunities. Nephrol Dial Transplant. 2013. 28(12):2961-8. doi: 10.1093/ndt/gft244
35. Lambert K., Mullan J., Mansfield K. An integrative review of the methodology and findings regarding dietary adherence in end stage kidney disease. BMC Nephrol. 2017. 18(1):318. doi: 10.1186/s12882-017-0734-z
36. Chan Y.M., Zalilah M.S., Hii S.Z. Determinants of compliance behaviours among patients undergoing hemodialysis in Malaysia. PLoS One. 2012. 7(8):e41362. doi: 10.1371/journal.pone.0041362
37. Hou S.H., Zhao J., Ellman C.F. et al. Calcium and phosphorus fluxes during hemodialysis with low calcium dialysate. Am J Kidney Dis. 1991. 18(2):217-24. doi: 10.1016/s0272-6386(12)80882-1
38. Milazi M., Bonner A., Douglas C. Effectiveness of educational or behavioral interventions on adherence to phosphate control in adults receiving hemodialysis: a systematic review. JBI Database System Rev Implement Rep. 2017. 15(4):971-1010. doi: 10.11124/JBISRIR-2017-003360
39. Denhaerynck K., Manhaeve D., Dobbels F. et al. Prevalence and consequences of nonadherence to hemodialysis regimens. Am J Crit Care. 2007. 16(3):222-235
40. Tohme F., Mor M.K., Pena-Polanco J. et al. Predictors and outcomes of non-adherence in patients receiving maintenance hemodialysis. Int Urol Nephrol. 2017. 49(8):1471-1479. doi: 10.1007/s11255-017-1600-4
41. Kutner N.G., Zhang R., McClellan W.M., Cole S.A. Psychosocial predictors of non-compliance in haemodialysis and peritoneal dialysis patients. Nephrol Dial Transplant. 2002. 17(1):93-99. doi: 10.1093/ndt/17.1.93. PMID: 11773470
42. O’Brien M.E. Compliance behavior and long-term maintenance dialysis. Am J Kidney Dis. 1990. 15(3):209-214. doi: 10.1016/s0272-6386(12)80764-5
43. 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):159. doi: https://doi.org/10.1016/j.kisu.2017.10.001
44. Tonelli M., Pannu N., Manns B. Oral phosphate binders in patients with kidney failure. N Engl J Med 2010. 362:1312-1324. doi: 10.1056/NEJMra0912522. PMID: 20375408
45. Hjemås B. J., Bøvre K., Mathiesen L. Interventional study to improve adherence to phosphate binder treatment in dialysis patients. BMC Nephrol. 2019. 20(1):178. doi: 10.1186/s12882-019-1334-x
46. Locatelli F., Del Vecchio L., Violo L., Pontoriero G. Phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a comparison of safety profiles. Expert Opin Drug Saf. 2014. 13(5):551-561. doi: 10.1517/14740338.2014.907791
47. Covic A., Floege Jü., Ketteler M., Sprague St. Iron-related parameters in dialysis patients treated with sucroferric oxyhydroxide. Nephrol Dial Transplant. 2016. (0):1-9. doi: 10.1093/ndt/gfw242
48. Coyne D.W., Ficociello L.H., Parameswaran V. et al. Real-world effectiveness of sucroferric oxyhydroxide in patients on chronic hemodialysis: A retrospective analysis of pharmacy data. Clin Nephrol. 2017. 88(8):59-67. doi: 10.5414/CN109021
49. Fouque D., Boletis I., Francisco A. et al. Real-world safety and effectiveness of sucroferric oxyhydroxide in dialysis patients: an interim analysis of the VERIFIE study. Nephrol Dial Transplant. (33 suppl.1) i:242. 2018. doi:10.1093/ndt/gfy104.FP593
50. Mittman N., Desiraju B., Meyer K.B. et al. Treatment of secondary hyperparathyroidism in ESRD: a 2-year, single-center crossover study. Kidney Int Suppl. 2010. 117:S33-S36. doi: 10.1038/ki.2010.191
51. Ong L.M., Narayanan P., Goh H.K. et al. Randomized controlled trial to compare the efficacy and safety of oral paricalcitol with oral calcitriol in dialysis patients with secondary hyperparathyroidism. Nephrology (Carlton). 2013. 18(3):194-200. doi: 10.1111/nep.12029
52. Quarles L.D., Yohay D.A., Carroll B.A. et al. Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD. Kidney Int. 1994. 45(6):1710-1721. doi: 10.1038/ki.1994.223
53. Martin K.J., Gonzalez E.A. Vitamin D analogs: actions and role in the treatment of secondary hyperparathyroidism. Semin Nephrol. 2004. 24(5):456-459. doi: 10.1016/j.semnephrol.2004.06.013
54. Brown A.J., Slatopolsky E. Drug insight: vitamin D analogs in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Nat Clin Pract Endocrinol Metab. 2007. 3(2):134-144. doi: 10.1038/ncpendmet0394
55. Sprague S.M., Llach F., Amdahl M. et al. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int. 2003. 63(4):1483-1490. doi: 10.1046/j.1523-1755.2003.00878.x
56. Tonbul H.Z., Solak Y., Atalay H. et al. Efficacy and tolerability of intravenous paricalcitol in calcitriol-resistant hemodialysis patients with secondary hyperparathyroidism: 12-month prospective study. Ren Fail. 2012. 34(3):297-303. doi: 10.3109/0886022X.2011.647298
57. Zella J.B., Plum L.A., Plowchalk D.R. et al. Novel, selective vitamin D analog suppresses parathyroid hormone in uremic animals and postmenopausal women. Am J Nephrol. 2014. 39(6):476-483. doi: 10.1159/000362846
58. Pandey R., Zella J.B., Zhu J.G. et al. Pharmacokinetics of a new oral vitamin d receptor activator (2-Methylene-19-Nor-(20S)-1α,25-Dihydroxyvitamin D(3)) in patients with chronic kidney disease and secondary hyperparathyroidism on hemodialysis. Drugs R D 2017. 17(4):597-605. doi: 10.1007/s40268-017-0210-z
59. Okuno S., Inaba M., Ishimura E. et al. Effects of long-term cinacalcet administration on parathyroid gland in hemodialysis patients with secondary hyperparathyroidism. Nephron. 2019. 142(2):106-13. doi: 10.1159/000496808
60. Behets G.J., Spasovski G., Sterling L.R. et al. Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism. Kidney Int. 2015. 87:846-856. doi: 10.1038/ki.2014.349
61. Chertow G.M., Block G.A., Correa-Rotter R. et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012. 367:2482-2494. doi: 10.1056/NEJMoa1205624
62. Moe S.M., Abdalla S., Chertow G.M. et al. Effects of cinacalcet on fracture events in patients receiving hemodialysis: the EVOLVE trial. J Am Soc Nephrol. 2015. 26:1466-1475. doi: 10.1681/ASN.2014040414
63. Louie K.S., Erhard C., Wheeler D.C. et al. Cinacalcet-induced hypocalcemia in a cohort of European haemodialysis patients: Predictors, therapeutic approaches and outcomes. J Nephrol 2020. 33(4):803-16. doi: 10.1007/s40620-019-00686-z
64. Xu J., Yang Y., Ma L. et al. Cinacalcet plus vitamin d versus vitamin d alone for the treatment of secondary hyperparathyroidism in patients undergoing dialysis: A meta-analysis of randomized controlled trials. Int Urol Nephrol. 2019. 51(11):2027-36. doi: 10.1007/s11255-019-02271-6
65. Ngamkam J., Vadcharavivad S., Areepium N., et al. The impact of CASR A990G polymorphism in response to cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism. Sci Rep 2021. 11(1):18006. doi: 10.1038/s41598-021-97587-8
66. Otsuka K., Ohno Y., Oshima J. Gallstones were associated with the gastrointestinal adverse events of cinacalcet in hemodialysis patients with secondary hyperparathyroidism. Ren Fail 2018. 40(1):38-42. doi: 10.1080/0886022x.2017.1419971
67. 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. doi: 10.1016/j.kint.2018.05.013
68. Harada K., Fujioka A., Konno M. et al. Pharmacology of parsabiv(®) (etelcalcetide, ONO-5163/AMG 416), a novel allosteric modulator of the calcium-sensing receptor, for secondary hyperparathyroidism in hemodialysis patients. Eur J Pharmacol. 2019. 842:139-45. doi: 10.1016/j.ejphar.2018.10.021
69. Yu L., Tomlinson J.E., Alexander S.T. et al. Etelcalcetide, a novel calcimimetic, prevents vascular calcification in a rat model of renal insufficiency with secondary hyperparathyroidism. Calcif Tissue Int. 2017. 101(6):641-53. doi: 10.1007/s00223-017-0319-7
70. Chen X.J., Chen X., Wu W.J. et al. Effects of FGF-23-mediated ERK/MAPK signaling pathway on parathyroid hormone secretion of parathyroid cells in rats with secondary hyperparathyroidism. J Cell Physiol. 2018. 233(9):7092-102. doi: 10.1002/jcp.26525
71. Fukagawa M., Yokoyama K., Shigematsu T. et al. A phase 3, multicenter, 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):1723-30. doi: 10.1093/ndt/gfw408
72. Massimetti C., Tondo M., Feriozzi S. [Long-term efficacy and safety of etelcalcetide in hemodialysis patients with severe secondary hyperparathyroidism]. G Ital Nefrol. 2020. 37(5):1397. doi: 10.1093/ndt/gfaa142.p1397
73. 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. doi: 10.1016/j.kint.2018.05.013
74. Sakai M., Tokunaga S., Kawai M. et al. Evocalcet prevents ectopic calcification and parathyroid hyperplasia in rats with secondary hyperparathyroidism. PloS One. 2020. 15(4): e0232428. doi: 10.1371/journal.pone.0232428

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