References

endoserg

Эндокринная хирургия

Endocrine Surgery

2306-35132310-3965

Типография «Печатных дел Мастер»

10.14341/2306-3513-2012-2-27-41

endoserg-4001

Research Article

Статьи

Articles

Лечение вторичного гиперпаратиреоза, рефрактерного к альфакальцидолу, у пациентов, получающих заместительную почечную терапию программным гемодиализом

The treatment of secondary hyperparathyroidism in haemodialysis patients' refractory to alfacalcidol

Egshatyan

L V

Rozhinskaya

L Ya

Kuznetsov

N S

Kim

I V

Artemova

A M

Mordik

A I

Pushkina

A V

Borisov

V N

Shilo

V. Yu.

Bukhman

A I

Remizov

O V

Ilin

A V

Sazonova

N I

Chernova

T O

2012

15062012

№2 (2012)

2741

Copyright © Egshatyan L.V., Rozhinskaya L.Y., Kuznetsov N.S., Kim I.V., Artemova A.M., Mordik A.I., Pushkina A.V., Borisov V.N., Shilo V.Y., Bukhman A.I., Remizov O.V., Ilin A.V., Sazonova N.I., Chernova T.O., 2012

2012

Egshatyan L.V., Rozhinskaya L.Y., Kuznetsov N.S., Kim I.V., Artemova A.M., Mordik A.I., Pushkina A.V., Borisov V.N., Shilo V.Y., Bukhman A.I., Remizov O.V., Ilin A.V., Sazonova N.I., Chernova T.O.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.surg-endojournals.ru/jour/article/view/4001

Вторичный гиперпаратиреоз (ВГПТ) является серьезным осложнением у пациентов с хронической болезнью почек(ХБП), поражающая костную и сердечно-сосудистую системы.Цель: оценить влияние Мимпары (Цинакальцет HCl) на показатели фосфорно-кальциевого обмена, костного метаболизма и минеральной плотности костей (МПК) в сравнении с паратиреоидэктомией (ПТЭ) у пациентов с терминальной стадией ХБП на гемодиализе, рефрактерных к терапии альфакальцидолом. Материал и методы. В 6=месячное исследование были включены 62 гемодиализных пациента с ВГПТ. Все пациенты имели показания к ПТЭ, основанные на клинико-лабораторных исследованиях. Лечение Мимпарой получали 40 пациентов. Доза титровалась каждые 4 недели, начальная составила 30 мг, максимальная –180 (средняя 59,1 ± 34,2) мг/сут. ПТЭ подверглись 22 пациента. Объем оперативного вмешательства зависел от количества гиперплазированных околощитовидных желез (ОЩЖ).Результаты. Через 6 месяцев средние уровни ПТГ, Ca, Са×Р, CTx и ОК статистически достоверно снизились на55,7%, 13,8%, 34,3%, 21,4 и 1,4% в группе Мимпары против 90,7%, 14%, 55,5%, 58,7% и 26,9% группы ПТЭ.У 94,3% пациентов, принимающих Мимпару, отмечается снижение иПТГ на более чем 30%, из них у 74,3% – на более чем 50% от исходного уровня. Целевые значения иПТГ достигнуты у 28,6% пациентов. Через 6 месяцев после ПТЭ уровень иПТГ у 50% пациентов был <100 пг/мл, у 27,3% соответствовал рекомендациям KDOQI, у 18,2% был >300 пг/мл. Выявлено значительное достоверное повышение уровня 25(ОН)D в группе ПТЭ (на 127,3%, p < 0,01) по сравнению с группой Мимпары (6,72%, p < 0,01). В отличие от достоверного прироста МПК после ПТЭ, на фоне терапии Мимпарой отмечается стабилизация показателей. Терапия Мимпарой способствует уменьшению объема ОЩЖ, как с исходным объемом <500 мм3, так и >500 мм3.Выводы. Результаты свидетельствуют об эффективности ПТЭ и Мимпары в стабилизации проявлений (нарушения фосфорно=кальциевого и костного обмена) ВГПТ у гемодиализных пациентов. В отличие от лечения Мимпарой, после ПТЭ маркеры костного метаболизма снижаются, МПК восстанавливается эффективнее. У части пациентов без выраженной ренальной остеодистрофии, возможно отказаться от проведения паратиреоидэктомии в пользу лечения Мимпарой.

Background. Secondary hyperparathyroidism (sHPT) is one of the serious complications in chronic kidney disease and is associated with progressive bone disease and vascular calcification.The objective of the study was to determine the impact of Mimpara (Cinacalcet HCl) on mineral disorder, bone turnover and bone mineral density (BMD) versus parathyroidectomy (PTx) in haemodialysis patients’ refractory to alfacalcidol. Materials and methods. 62 haemodialysis patients with sHPT were enrolled in this 6=months prospective study. All of them had surgical indications for PTx. Surgical indications was established according to clinical or biological assessment. 40 patients underwent Mimpara treatment. Dose of Mimpara was titrated every 4 weeks. Sequential doses included 30–180 (mean 59.1 ± 34.2) mg/day. 22 patients underwent PTx. The surgical technique was depended on quantity of hyperplastic parathyroid glands.Results. In 6 months mean iPTH, Ca, Са×Р, CTx and OC levels significantly decreased by 55.7%, 13.8%,34.3%, 21.4 and 1.4% in the Mimpara group vs. 90.7%, 14%, 55.5%, 58.7% and 26.9% in the PTx group. Median serum iPTH level decreased by 30% after initiation of Mimpara in 94.3% patients, from them by 50%in 74.3%. Achieved the KDOQI treatment targets for PTH in 28.6% patients.In 6 months after PTx median serum iPTH level was <100 pg/ml in 50% patients, achieved the KDOQI treatment targets in 27.3%, <300 pg/ml in 18.2%. Median serum 25(ОН)D after PTx significantly increase by 127.3% vs 6.72% in the Mimpara group. In 6 months active restoration of BMD was found in the PTx patients, and patients treated with Cinacalcet showed stabilization of BMD.Mimpara therapy led to a reduction in glandular volume during the course of the study: in both glands with a baseline volume <500 mm3 and with a baseline volume ≥500 mm3. Conclusions. PTx and Cinacalcet therapy improves phosphorus=calcium homeostasis, bone turnover, but bone resorption and formation markers decreased better in the PTx group compared to Cinacalcet group. The effectiveness and safety of Mimpara for secondary hyperparathyroidism were evaluated in dialysis patients’ refractory to alfacalcidol, which reduced the need for parathyroidectomy in patient without severe osteodystrophy.

вторичный гиперпаратиреозгемодиализпаратиреоидэктомияМимпара

Secondary hyperparathyroidismhaemodialysisparathyroidectomyMimpara(Cinacalcet HCl)

References1

Angel L.M. De Francisco, Gema Fern andez Fresnedo, Emilio Rodrigo et al. Parathyroidectomy in dialysis patients. Kidney International 2002; 61: S161–S166; doi:10.1046/ j.1523–1755.61.s80.27.x

Arciero C.A., Peoples G.E., Stojadinovic A. et al. The utility of a rapid parathyroid assay for uniglandular, multiglandular, and recurrent parathyroid disease. Am. Surg. 2004; 70: 588–592.

Block G.A., Port F.K. Re=evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: recommendations for a change in management. Am. J. Kidney Dis. 2000; 35: 1226–1237/

Chin J., Miller S.C., Wada M. et al. Activation of the calcium receptor by a calcimimetic compound halts the progression of secondary hyperparathyroidism in uremic rats. J. Am. Soc. Nephrol. 2000; 11: 903–911. Лечение вторичного гиперпаратиреоза, рефрактерного к альфакальцидолу.. Л.В. Егшатян и соавт.

Chou F.F., Chen J.B., Lee C.H., Chen S.H., Sheen)Chen S.M. Parathyroidectomy can improve bone mineral density in patients with symptomatic secondary hyperparathyroidism. Arch. Surg. 2001; 136: 1064–1068.

Coco M., Rush H. Increased. Am. J. Kidney Dis. 2000; 36: 1115–1121.

Colloton M., Shatzen E., Miller G. et al. Cinacalcet HCl atten= uates parathyroid hyperplasia in a rat model of secondary hyperparathyroidism. Kidney Int. 2005; 67: 467–476.

Cunningham J., Danese M. et al. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health=related quality of life in secondary hyperparathy= roidism. Kidney Int. 2005; 68: 1793–1800.

Dotzenrath C., Cupisti K., Goretzki E., Mondry A. et al. Operative treatment of renal autonomous hyperparathyroidism: cause of persistent or recurrent disease in 304 patients. Langenbecks Arch. Surg. 2003; 387 (9–10): 348–354.

Drüeke T.B., Zingraff J. The dilemma of parathyroidectomy in chronic renal failure. Curr. Opin. Nephrol. Hypertens. 1994;3 (4): 386–395.

Fassbinder W., Brunner F.P., Brynger H. et al. Combined report on regular dialysis and transplantation in Europe. XX, 1989; Nephrol. Dial. Transplant 1991; 6 (Suppl 1): 4–65.

Floege J., Kim J., Ireland E. et al. Fouqueray B., Wheeler D.C.; on behalf of the ARO Investigators: Serum iPTH, calci= um and phosphate, and the risk of mortality in a European haemodialysis population. Nephrol. Dial. Transplant. 2010: Apr. 25. Epub ahead of print.

Foley R.N., Li S., Liu J. et al. The fall and rise of parathyroidectomy in U.S. hemodialysis patients, 1992 to 2002. J. Am. Soc. Nephrol. 2005; 16: 210.

Fournier A., Drüeke T. & Moriniére P.H. et al. The new treatments of hyperparathyroidism secondary to renal insufficien= cy. Adv. Nephrol. Necker. Hosp. 1992; 21: 237–306.

Fox J., Lowe S.H., Conklin R.L., Nemeth E.F. The calcimimet ic NPS R=568 decreases plasma PTH in rats with mild and severe renal or dietary secondary hyperparathyroidism. Endocrine 1999; 10: 97–103.

Guido Gasparri, Michele Camandona et al. Secondary and Tertiary Hyperparathyroidism: Causes of Recurrent Disease After 446 Parathyroidectomies. Ann. Surg. 2001; 233 (1): 65–69.

Ganesh S.K., Stack A.G., Levin N.W. et al. Association of elvated serum PO4, Ca×PO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J. Am. Soc. Nephrol. 2001; 12: 2131–2138.

Gourgiotis S., Moustafellos P., Stratopoulos C. et al. Total parathyroidectomy with autotransplantation in patients with renal hyperparathyroidism: indications and surgical approach. Hormones (Athens) 2006; 5: 270–275.

Hauache O.M., Hu J., Ray K. et al. Effects of a calcimimetic compound and naturally activating mutations on the human Ca2+ receptor and on Ca2+ receptor/metabotropic glutamate chimeric receptors. Endocrinology 2000; 141: 4156–4163.

Bover J., Perez R., Molina M. et al. Josep Vicens Torregrosa, on behalf of the Renal Osteodystrophy Group of the Spanish Society of Nephrology and all the investigators from the REHISET study. Cinacalcet Treatment for Secondary Hyperparathyroidism in Dialysis Patients: An Observational Study in Routine Clinical Practice. Nephron. Clin. Pract. 2011; 118: 109–121.

Jofre R., Lopez Gomez J.M., Menarguez J. et al. Parathroid= ectomy: Whom and When? Kidney Int. Suppl. 2003; 85: 97–100.

Lorenz K., Ukkat J., Sekulla C. et al. Total Parathyroidectomy Without Autotransplantation for Renal Hyperparathyroidism: Experience with a qPTH=controlled Protocol. World. J. Surg. 2006; 30: 743–751.

Katagiri M., Fukunaga M., Ohtawa T., Harada T. Prediction of Bone Mass in Renal Hyperparathyroidism by Newly Developed Bone Metabolic Markers: Evaluation of Serum Levels of G. Mircescu , B. Stanescu 572 Carboxy=Terminal Pyridinoline Cross=Linked Telopeptide of Type I Collagen and Carboxy=Terminal Propeptide of Type I Procollagen. World. J. Surg. 1996; 20: 753–757.

Kaye M., Rosenthall L., Hill R.O. et al. Long term outcome fol= lowing total parathyroidectomy in patients with end stage renal disease. Clin. Nephol. 1993; 39: 192–197.

Kestenbaum B., Belozeroff V. Mineral metabolism distur= bances in patients with chronic kidney disease. Eur. J. Clin. Invest. 2007; 37, (N. 8): 607–622.

Kidney Disease: Improving Global Outcomes (KDIGO) CKD= MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease=mineral and bone disorder (CKD=MBD). Kidney Int. Suppl. 2009; 113: 1–130.

Kitagawa W, Shimizu K, Akasu H. Endocrine surgery: the tenth report. Diagnosis, surgical indications and operative strategy of renal hyperparathyroidism J. Nippon. Med. Sch. 2003; 70 (3): 278–82.

Komaba H., Takeda Y., Abe T. et al. Spontaneous remission of severe hyperparathyroidism with normalization of the reversed whole PTH/intact PTH ratio in a haemodialysis patient. Nephrol. Dial. Transplant. 2008; 23: 1760–1762.

Koosman M., Hughes K., Dickerman R. et al. Parathyroid= ectomy in chronic renal failure. Am. J. Surg. 1994; 168: 631–635.

Lindberg J.S., Culleton B., Wong G. et al. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyper= parathyroidism in hemodialysis and peritoneal dialysis: a ran= domized, double=blind, multicenter study. J. Am. Soc. Nephrol. 2005; 16: 800–807.

Ljutic D., Cameron J.S., Ogg C.S. et al. Long term follow=up after total parathyroidectomy without parathyroid reimplanta= tion in chronic renal failure. Q. J. Med. 1994; 87: 685–692.

Llach F. Parathyroidectomy in chronic renal failure: indica= tions, surgical approach and use of calcitriol. Kidney Int. Suppl. 1990; 29: 62–68.

Llach F., Velasquez Forero. Secondary hyperparathyroidism in chronic renal failure: Pathogenic and clinical aspects. Am. J. Kidney. Dis. 2001; 38 (5): 20–33.

Lorenz K., Dralle H. Editorial. Will intraoperative measure= ment of parathyroid hormone alter the surgical concept of renal hyperparathyroidism? Langenbecks Arch. Surg. 2005;390 (4): 277–279.

Malberti F., Marcelli D., Conte F. et al. Parathyroidectomy in patients on renal replacement therapy: an epidemiologic study. J. Am. Soc. Nephrol. 2001; 12: 1242–1248.

Malluche H.H., Monier)Faugere M.C. et al. An assessment of cinacalcet HCl effects on bone histology in dialysis patients with secondary hyperparathyroidism. Clin. Nephrol. 2008; 69: 269–278.

Maxwell P.H., Winearls C.G. Recurrence of autonomous hyperparathyroidism in dialysis patients. Nephrol. Dial. Transplant. 1997; 12: 2195–2200.

Meola M., Petrucci I., Barsotti G. Long=term treatment with cinacalcet and conventional therapy reduces parathyroid hyperplasia in severe secondary hyperparathyroidism. Nephrol. Dial. Transplant. 2009; 24: 982–989.

Messa P., Macario 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: 36–45.

Mizobuchi M., Ogata H., Hatamura I. et al. Activation of calci= um=sensing receptor accelerates apoptosis in hyperplastic parathyroid cells. Biochem. Biophys. Res. Commun. 2007; 362: 11–16.

Moe S.M., Chertow G.M., Coburn J.W. et al. Achieving NKF=K/ DOQI bone metabolism and disease treatment goals with cinacalcet H.C.l. Kidney Int. 2005; 67: 760–771.

Mucsi I., Hercz G. Adynamic bone disease: Pathogenesis, diagnosis and clinical relevance. Curr. Opin. Nephrol. Hypertens. 1997; 6: 356–361.

National Kidney Foundation: K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney dis= ease. Am. J. Kidney Dis. 2003; 42(suppl 3): 1–201.

Nemeth E.F., Steffey M.E., Hammerland LG. et al. Calci= mimetics with potent and selective activity on the parathyroid calcium receptor. Proc. Natl. Acad. Sci. U.S.A. 1998; 95: 4040–4045.

Neonakis E., Wheeler M.H., Krishnan H. et al. Results of sur= gical treatment of renal hyperparathyoidism. Arch. Surg. 1995; 130: 643–648.

Nicholson M.L., Veitch P.S., Feehally J. Parathyroidectomy in chronic renal failure. A comparison of 3 operative strategies. J. R. Coll. Edinb. 1996; 41: 382.

Nordenstrom E., Westerdahl J., Bergenfelz A. Recovery of bone mineral density in 126 patients after surgery for primary hyperparathyroidism. World J. Surg. 2004; 28: 502–507.

O’Leary D.P., White H.J.O. Parathyroidectomy for hyper= parathyroidism associated with renal disease. Ann. R. Coll. Surg. Engl. 1995; 77: 97–101.

Ockert S., Willeke F., Richter A. et al. Total parathyroidecto= my without autotransplantation as standard procedure in the treatment of secondary hyperparathyroidism. Langenbecks Arch. Surg. 2002; 387: 204–209.

Ogg C.S. Total parathyroidectomy in treatment of secondary (renal) hyperparathyroidism. Br. Med. J. 1967; 4 (5575): 331–334.

Owda A., Elhwairis H., Narra S. et al. Secondary hyper= parathyroidism in chronic hemodialysis patients: prevalence and race. Ren. Fail. 2003; 25: 595–602.

Padhi D., Harris R.Z., Salfi M. et al. Pharmacokinetics and pharmacodynamics of cinacalcet in hepatic impairment: phase I, open=label, parallel=group, single=dose, single=cen= tre study. Clin. Drug. Investig. 2008; 28: 635–643.

Pasch A. Bone mass gain after parathyroidectomy. Kidney Int. 2008; 74: 697–699.

Saunders R., Karoo R., Metcalfe M.S., Nicholson M.L. Four gland parathyroidectomy without reimplantation in patients with chronic renal failure. Postgrad. Med. J. 2005; 81: 255–258.

Reichel H., Deibert B., Schmidt)Gayk H., Ritz E. Calcium metabolism in early chronic renal failure: Implications for the pathogenesis of hyperparathyroidism. Nephrol. Dial. Trans= plant. 1991; 6: 162–169.

Richards M.L. Wormuth J. Bingener J. Sirinek K. Parathyroid= ectomy in secondary hyperparathyroidism: Is there an opti= mal operative management? Surgery. 2006; 139 (2): 174–180.

Rodriguez M., Caravaca F., Fernandez E. et al. Parathyroid function as a determinant of the response to calcitriol treat= ment in the hemodialysis patient. Kidney Int. 1999; 56: 306–317.

Rudser K.D. de Boer I.H., Dooley A., Young B., Kestenbaum B. Fracture Risk after Parathyroidectomy among Chronic Hemodialysis Patients. J. Am. Soc. Nephrol. 2007; 18: 2401–2407.

Schaefer R.M., Bover J., Dellanna F. et al. Efficacy of cinacal= cet administered with the first meal after dialysis: the SEN= SOR Study. Clin. Nephrol. 2008; 70: 126–134.

Silver J., Naveh)Many T. Phosphate and the parathyroid. Kidney Int. 2009; 75: 898–905.

Silver J., Naveh)Many T., Mayer H. et al. Regulation by vita= min D metabolites of parathyroid hormone gene transcription in vivo in the rat. J. Clin. Invest. 1986; 78: 1296–1301.

Silverberg S.J., Gartenberg F., Jacobs T.P. et al. Increased bone mineral density after parathyroidectomy in primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 1995; 80: 729–734.

Slatopolsky E., Delmez J. Pathogenesis of secondary hyperparathyroidism. Neprol. Dial. Transplant. 1996; 11, (3): 130–136.

St Peter W.L., Li Q., Liu J. et al. Cinacalcet use patterns and effect on laboratory values and other medications in a large dialysis organization, 2004 through 2006. Clin. J. Am. Soc. Nephrol. 2009; 4: 354–360.

Stehman)Breen C., Muirhead N., Thorning D., Sherrard D. Secondary hyperparathyroidism complicated by parathyro= matosis. Am. J. Kidney. Dis. 1996; 28: 502–507.

Sterrett J.R., Strom J., Stummvoll H.K. et al. Cinacalcet H.C.l. (Sensipar/Mimpara) is an effective chronic therapy for hemodialysis patients with secondary hyperparathyroidism. Clin. Nephrol. 2007; 68: 10–17.

Strippoli G.F., Tong A., Palmer S.C. et al. Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients. Cochrane Database Syst. Rev. 2006; 18 (4): CD006254 Review

Tanaka M., Tominaga Y., Sawatari E. et al. Infarction of mediastinal parathyroid gland causing spontaneous remission of secondary hyperparathyroidism. Am. J. Kidney Dis. 2004; 44: 762–767.

Terawaki H., Nakano H., Takeguchi F. et al. Regression of parathyroid gland swelling by treatment with cinacalcet. Nephrol. Dial. Transplant. 2009; 24: 691–692.

Tominaga Y., Numano M., Tanaka Y. et al. Surgical Treatment of Renal Hyperparathyroidism. Sem. Surg. Oncol. 1997; 13: 87–96.

Tominaga Y., Kazuaru U., Toshihito H. More than 1000 cases of parathyroidectomy with forearm autograft for renal hyper= parathyroidism. Am. J. Kidney. Dis. 2001; 38 Suppl: 168–171.

Tominaga Y., Tanaka Y., Sato K. et. аl. Histopathology, pathophysiology and indications for surgical treatment of renal hyperparathyroidism. Semin. Surg. Oncol. 1997; 13: 78?86

Urena P., Jacobson S.H., Zitt E. et. al. Cinacalcet and achievement of the NKF/K=DOQITM recommended target values for bone and mineral metabolism in real=world clinical practice – the ECHO observational study. Nephrol. Dial. Transplant. 2009; 24: 2852–2859.

Valderrabano F., Golper T., Muirhead N. et al. Chronic kidney disease: why is current management uncoordinated and sub= optimal? Nephrol. Dial. Transplant. 2001; 16: 61–64.

Wada M., Furuya Y., Sakiyama J. et al. The calcimimetic compound NPS R=568 suppresses parathyroid cell proliferation in rats with renal insufficiency. Control of parathyroid cell growth via a calcium receptor. J. Clin. Invest. 1997; 100: 2977–2983.

Yajima A., Inaba M., Tominaga Y., Ito A. Bone formation by minimodeling is more active than remodeling after parathy= roidectomy.Kidney Int. 2008; 74: 775–781.

Yamashita H., Cantor T., Uchino S. et al. Sequential changes in plasma intact and whole parathyroid hormone levels during parathyroidectomy for secondary hyperparathyroidism. World. J. Surg. 2005; 29: 169–173.

Yano S., Sugimoto T., Tsukamoto T. et al. Effect of parathyroidectomy on bone mineral density in hemodialysis patients with secondary hyperparathyroidism: Possible usefulness of preoperative determination of parathyroid hormone level for prediction of bone regain. Horm. Metab. Res. 2003; 35: 259–264,.

Yatsuka H., Tominaga Y. Regulatory Subunit in Nodular Hyperplasia of Parathyroid in Patients with Chronic Renal Failure. Materials from conference of endocrinologist. Honkong, 2006; p39.

Zimmermann G., Neyer U., Haid A. et al. Erfahrungen mit der totalen Parathyreoidektomie und Autotransplantation intra= operativ ausgewa. hlten Parathyreoidea=Gewebes beim reak= tiven renalen Hyperparathyreoidismus. Wien. Klin. Wochen= schr. 1992; 104: 434–438.

“Official Positions of the International Society for Clinical Densitometry”, Corperight ISCD, October 2007, Supersedes all prior “Official Positions” publications.

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