nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное обществоnid-1036Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESКоррекция вторичного гиперпаратиреоза (ВГПТ) внутривенным введением альфакальцидола у пациентов на программном гемодиализе (ГД)Correction of secondary hyperparathyroidism (SHPT) with intravenous alfacalcidol in patients on program hemodialysisБорисовА. В.BorisovA. V.avborisov@yandex.ruМордикА. И.MordikA. I.noemail@neicon.ruБорисоваЕ. В.BorisovaE. V.noemail@neicon.ruЕрмаковаИ. П.ErmakovaI. P.noemail@neicon.ruРожинскаяЛ. Я.RozhinskayaL. Y.noemail@neicon.ruЦЭТ «Фесфарм»Russian FederationНИИТиИО МЗ и СР РФRussian FederationГУ ЭНЦ РАМН; г. МоскваRussian Federation200919062025113236241Copyright © Борисов А.В., Мордик А.И., Борисова Е.В., Ермакова И.П., Рожинская Л.Я., 20252025Борисов А.В., Мордик А.И., Борисова Е.В., Ермакова И.П., Рожинская Л.Я.Borisov A.V., Mordik A.I., Borisova E.V., Ermakova I.P., Rozhinskaya L.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/1036

Исследовано влияние пульс-терапии внутривенным альфакальцидолом (ЭТАЛЬФА) у 16 пациентов с вторичным гиперпаратиреозом (ВГПТ), находящихся на лечении программным ГД. Средние дозы ЭТАЛЬФА зависели от выраженности ВГПТ и составили от 3 до 9 мкг в неделю. Лечение состояло из нескольких этапов, включавших в себя внутривенное (в/в) и пероральное (п/о) применение альфакальцидола. Общая продолжительность исследования составила 11 месяцев. Прогрессирование ВГПТ наблюдалось у 2 пациентов (13%), у 14 (87%) достигнуто снижение интактного паратиреоидного гормона (иПТГ). У пациентов с выраженным ВГПТ, ответивших на лечение, иПТГ снизился на 50% (М ± SD 1185,6 ± 374; 612,2 ± 377 пг/мл), при умеренном ВГПТ иПТГ уменьшился на 63% от исходного (623,27 ± 121; 228,27 ± 123,06 пг/мл). Целевой иПТГ (<300 пг/мл) достигнут у 3 пациентов (19%), у 3 (19%) наблюдалась чрезмерная супрессия паращитовидных желез (иПТГ <150 пг/мл). У всех пациентов, даже у тех, у кого отмечался прогрессирующий рост иПТГ, наблюдалось снижение маркеров как костеобразования (ЩФ и КЩФ), так и резорбции кости (b-кросслап – БКЛ). Терапия альфакальцидолом приводила к нормализации маркеров резорбции у 12 (75%) из 16 и маркеров формирования у 13 (81%) пациентов. Сравнение п/о и в/в терапии ЭТАЛЬФА показало преимущество внутривенного введения препарата из-за возможности применения более высоких доз, необходимых для контроля за паратиреоидной функцией, при меньшем влиянии на показатели фосфорно-кальциевого гомеостаза

The effect of intravenous ”pulse-therapy” with alfacalcidol (ETALPHA) was studied in 16 dialysis SHPT patients. Average doses of ETALPHA depended on the severity of SHPT and ranged from 3 to 9 mg per week. The treatment consisted of several stages and included intravenous and oral therapy with alfacalcidol. The total duration of the study was 11 months. Resolution of SHPT was observed in 2 patients (13%), in 14 patients (87%) a decrease in serum iPTH level was achieved. In those patients with severe SHPT who responded to the treatment serum iPTH decreased by 50% (from 1185,6 ± 374 to 612,2 ± 377 pg/ml, М ± SD). In patients with moderate SHPT serum iPTH level decreased by 63% from the baseline of 623,27 ± 121 to 228,27 ± 123,06 pg/ml. A target iPTH level (<300 pg/ml) was achieved in 3 patients (19%), oversupression of parathyroid hormone production was detected in 3 patients (19%). Normalization of bone formation markers (alkaline phosphatase and bone specific alkaline phosphatase) and of bone resorbtion marker (b-crosslaps) was observed in all patients including those who had progressive increase of the iPTH level. Treatment with alfacalcidol led to normalization of bone resorbtion markers in 12 patients (75%) and of bone formation markers in 13 patients (81%). Conclusion. Intravenous alfacalcidol therapy has advantage over oral treatment because it gives the opportunity to use higher doses of alfacalcidol, which may be needed to control parathyroid glands function, with lower risk of violation of calcium-phosphorus metabolism.

ВГПТгемодиализальфакальцидол (этальфа)иПТГминеральный обменмаркеры костного метаболизмаReferencesЕрмакова И.П., Пронченко И.А., Бузулина В.П., Никонова Т.Ю., Борисов А.В. Значение биохимических маркеров формирования кости при гемодиализе и после аллотрансплантации трупной почки // Тер. архив. 2006. № 10. С. 73–76.Ермакова И.П., Пронченко И.А., Бузулина В.П., Никонова Т.Ю., Борисов А.В. Значение биохимических маркеров формирования кости при гемодиализе и после аллотрансплантации трупной почки // Тер. архив. 2006. № 10. С. 73–76.Bacchini G., Fabrizi F., Pontoriero G., Marcelli D., Di Filippo S., Locatelli F. ‘Pulse oral’ versus intravenous calcitriol therapy in chronic hemodialysis patients. A prospective and randomized study // Nephron. 1997. V. 77: P. 267–272.Bacchini G., Fabrizi F., Pontoriero G., Marcelli D., Di Filippo S., Locatelli F. ‘Pulse oral’ versus intravenous calcitriol therapy in chronic hemodialysis patients. A prospective and randomized study // Nephron. 1997. V. 77: P. 267–272.Block G.A., Hulbert-Shearon T.E., Levin N.W., Port F.K. Association of serum phosphorus and calciumxphosphate product with mortality risk in chronic hemodialysis patients: A national study // Am J Kidney Dis. Apr 1998. V. 31. issue 4. P. 607–617.Block G.A., Hulbert-Shearon T.E., Levin N.W., Port F.K. Association of serum phosphorus and calciumxphosphate product with mortality risk in chronic hemodialysis patients: A national study // Am J Kidney Dis. Apr 1998. V. 31. issue 4. P. 607–617.Block G.A., Klassen P.S., Lazarus J.M., Ofsthun N., Lowrie E.G., Chertow G.M. Mineral Metabolism, Mortality, and Morbidity in Maintenance Hemodialysis // J Am Soc Nephrol. Aug 2004. V. 15. P. 2208–2218.Block G.A., Klassen P.S., Lazarus J.M., Ofsthun N., Lowrie E.G., Chertow G.M. Mineral Metabolism, Mortality, and Morbidity in Maintenance Hemodialysis // J Am Soc Nephrol. Aug 2004. V. 15. P. 2208–2218.Brandi L., Daugaard H., Egsmose C., Tvedegaard E., Kjaerulff Nielsen P., Olgaard K. Intermittent intravenous followed by intermittent oral 1 alpha(OH)D3 treatment of secondary hyperparathyroidism in uraemia // J Intern Med. Apr 1996. V. 239 (4). P. 353–360.Brandi L., Daugaard H., Egsmose C., Tvedegaard E., Kjaerulff Nielsen P., Olgaard K. Intermittent intravenous followed by intermittent oral 1 alpha(OH)D3 treatment of secondary hyperparathyroidism in uraemia // J Intern Med. Apr 1996. V. 239 (4). P. 353–360.Brandi L., Daugaard H., Tvedegaard E., Storm T., Olgaard K. Effect of intravenous 1-alpha-hydroxyvitamin D3 on secondary hyperparathyroidism in chronic uremic patients on maintenance hemodialysis // Nephron. 1989. V. 53 (3). P. 194–200.Brandi L., Daugaard H., Tvedegaard E., Storm T., Olgaard K. Effect of intravenous 1-alpha-hydroxyvitamin D3 on secondary hyperparathyroidism in chronic uremic patients on maintenance hemodialysis // Nephron. 1989. V. 53 (3). P. 194–200.Cannella G., Bonucci E., Rolla D. et al. Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol // Kidney Int. 1994. V. 46. P. 1124–1132.Cannella G., Bonucci E., Rolla D. et al. Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol // Kidney Int. 1994. V. 46. P. 1124–1132.Dennis L., Andress А. Intravenous versus oral vitamin D therapy in dialysis patients: What is the question? // Am J Kidney Dis. Nov 2001. V. 38. Iss 5 (Suppl 5). P. 41–44.Dennis L., Andress А. Intravenous versus oral vitamin D therapy in dialysis patients: What is the question? // Am J Kidney Dis. Nov 2001. V. 38. Iss 5 (Suppl 5). P. 41–44.Guillaume J., Charles C., Bernard C. Hyperphosphataemia and related mortality // NDT. 2006. V. 21. P. 273–280.Guillaume J., Charles C., Bernard C. Hyperphosphataemia and related mortality // NDT. 2006. V. 21. P. 273–280.Haddad A., Abbadi R., Marji A., Akash N. Pulse Intravenous vs pulse oral Alfacalcidol in hemodialysis patients with secondary hyperparathyroidism // Dial and Transpl. Aug 2004. V. 33. N 8. P. 492–496.Haddad A., Abbadi R., Marji A., Akash N. Pulse Intravenous vs pulse oral Alfacalcidol in hemodialysis patients with secondary hyperparathyroidism // Dial and Transpl. Aug 2004. V. 33. N 8. P. 492–496.Lind L., Wengle B., Wide L., Wrege U., Ljunghall S. Suppression of serum parathyroid hormone levels by intravenous alphacalcidol in uremic patients on maintenance hemodialysis // A pilot study: Nephron. 1988. V. 48 (4). P. 296–299.Lind L., Wengle B., Wide L., Wrege U., Ljunghall S. Suppression of serum parathyroid hormone levels by intravenous alphacalcidol in uremic patients on maintenance hemodialysis // A pilot study: Nephron. 1988. V. 48 (4). P. 296–299.Malluche H.H., Monier-Faugere M.C., Koszewski N.J. Use and indication of vitamin D and vitamin D analogues in patients with renal bone disease // NDT. 2002. V. 17. Suppl. 10. P. 6–9.Malluche H.H., Monier-Faugere M.C., Koszewski N.J. Use and indication of vitamin D and vitamin D analogues in patients with renal bone disease // NDT. 2002. V. 17. Suppl. 10. P. 6–9.Moallem E., Kilav R., Silver J. et al. RNA-protein binding and post transcriptional regulation of parathyroid gene expression by calcium and phosphate // J Bone Chem. 1998. V. 9. P. 5253–5259.Moallem E., Kilav R., Silver J. et al. RNA-protein binding and post transcriptional regulation of parathyroid gene expression by calcium and phosphate // J Bone Chem. 1998. V. 9. P. 5253–5259.National Kidney Foundation K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease // Am J Kidney Dis. 2003. 42 (suppl. 3).National Kidney Foundation K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease // Am J Kidney Dis. 2003. 42 (suppl. 3).Reichel H., Szabo A., Uhl J. et al. Intermittent versus continuous administration of 1,25-dihydroxyvitamin D3 in experimental renal hyperparathyroidism // Kidney Int. 1993. V. 44. P. 1259–1265.Reichel H., Szabo A., Uhl J. et al. Intermittent versus continuous administration of 1,25-dihydroxyvitamin D3 in experimental renal hyperparathyroidism // Kidney Int. 1993. V. 44. P. 1259–1265.Silver J., Naveh-Many T., Mayer H., Schmelzer H.J., Popovtzer M.M. Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat // J Clin Invest. 1986 Nov. 78 (5). P. 1296–1301.Silver J., Naveh-Many T., Mayer H., Schmelzer H.J., Popovtzer M.M. Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat // J Clin Invest. 1986 Nov. 78 (5). P. 1296–1301.Slatopolsky E., Weerts C., Thielan J., Horst R., Harter H., Martin K.J. Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxycholecalciferol in uremic patients // J Clin Invest. 1984. 74. P. 2136–2143.Slatopolsky E., Weerts C., Thielan J., Horst R., Harter H., Martin K.J. Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxycholecalciferol in uremic patients // J Clin Invest. 1984. 74. P. 2136–2143.Szabo A., Merke J., Beier E., Mall G., Ritz E. 1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia // Kidney Int. 1989 Apr. 35 (4). P. 1049–1056.Szabo A., Merke J., Beier E., Mall G., Ritz E. 1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia // Kidney Int. 1989 Apr. 35 (4). P. 1049–1056.Urena P., Bernard-Poenaru O., Cohen-Solal M. et al. Plasma bone-specific alkaline phosphatase changes in hemodialysis patients treated by alfacalcidol // Clin Nephrol. 2002. 57: P. 261–273.Urena P., Bernard-Poenaru O., Cohen-Solal M. et al. Plasma bone-specific alkaline phosphatase changes in hemodialysis patients treated by alfacalcidol // Clin Nephrol. 2002. 57: P. 261–273.

The authors declare that there are no conflicts of interest present.