Медицинская литература. Новинки

 

 

 

 

 

 

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

Вы можете загрузить полный текст статьи в формате pdf

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 на 55,7%, 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.

Ключевые слова:
вторичный гиперпаратиреоз, гемодиализ, паратиреоидэктомия, Мимпара

Литература:
1. 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
2. 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.
3. 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/
4. 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.
5. 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.
6. Coco M., Rush H. Increased. Am. J. Kidney Dis. 2000; 36:
1115–1121.
7. 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.
8. Cunningham J., Danese M. et al. Effects of the calcimimetic
cinacalcet HCl on cardiovascular disease, fracture, and
health=related quality of life in secondary hyperparathyroidism. Kidney Int. 2005; 68: 1793–1800.
9. 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.
10. Drüeke T.B., Zingraff J. The dilemma of parathyroidectomy in
chronic renal failure. Curr. Opin. Nephrol. Hypertens. 1994;
3 (4): 386–395.
11. 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.
12. Floege J., Kim J., Ireland E. et al. Fouqueray B., Wheeler
D.C.; on behalf of the ARO Investigators: Serum iPTH, calcium and phosphate, and the risk of mortality in a European
haemodialysis population. Nephrol. Dial. Transplant. 2010:
Apr. 25. Epub ahead of print.
13. Foley R.N., Li S., Liu J. et al. The fall and rise of parathy=
roidectomy in U.S. hemodialysis patients, 1992 to 2002. J.
Am. Soc. Nephrol. 2005; 16: 210.
14. Fournier A., Drüeke T. & Moriniére P.H. et al. The new treatments of hyperparathyroidism secondary to renal insufficiency. Adv. Nephrol. Necker. Hosp. 1992; 21: 237–306.
15. Fox J., Lowe S.H., Conklin R.L., Nemeth E.F. The calcimimetic NPS R=568 decreases plasma PTH in rats with mild and
severe renal or dietary secondary hyperparathyroidism.
Endocrine 1999; 10: 97–103.
16. Guido Gasparri, Michele Camandona et al. Secondary and
Tertiary Hyperparathyroidism: Causes of Recurrent Disease
After 446 Parathyroidectomies. Ann. Surg. 2001; 233 (1):
65–69.
17. Ganesh S.K., Stack A.G., Levin N.W. et al. Association of elevated serum PO4, Ca×PO4 product, and parathyroid hormone
with cardiac mortality risk in chronic hemodialysis patients.
J. Am. Soc. Nephrol. 2001; 12: 2131–2138.
18. 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.
19. 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.
20. 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.
21. Jofre R., Lopez Gomez J.M., Menarguez J. et al. Parathroidectomy: Whom and When? Kidney Int. Suppl. 2003; 85:
97–100.
22. 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.
23. 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.
24. Kaye M., Rosenthall L., Hill R.O. et al. Long term outcome following total parathyroidectomy in patients with end stage
renal disease. Clin. Nephol. 1993; 39: 192–197.
25. Kestenbaum B., Belozeroff V. Mineral metabolism disturbances in patients with chronic kidney disease. Eur. J. Clin.
Invest. 2007; 37, (N. 8): 607–622.
26. Kidney Disease: Improving Global Outcomes (KDIGO) CKDMBD 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.
27. 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.
28. 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.
29. Koosman M., Hughes K., Dickerman R. et al. Parathyroidectomy in chronic renal failure. Am. J. Surg. 1994; 168:
631–635.
30. Lindberg J.S., 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: 800–807.
31. Ljutic D., Cameron J.S., Ogg C.S. et al. Long term follow-up
after total parathyroidectomy without parathyroid reimplantation in chronic renal failure. Q. J. Med. 1994; 87: 685–692.
32. Llach F. Parathyroidectomy in chronic renal failure: indications, surgical approach and use of calcitriol. Kidney Int.
Suppl. 1990; 29: 62–68.
33. Llach F., Velasquez Forero. Secondary hyperparathyroidism
in chronic renal failure: Pathogenic and clinical aspects. Am.
J. Kidney. Dis. 2001; 38 (5): 20–33.
34. Lorenz K., Dralle H. Editorial. Will intraoperative measurement of parathyroid hormone alter the surgical concept of
renal hyperparathyroidism? Langenbecks Arch. Surg. 2005;
390 (4): 277–279.
35. 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.
36. 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.
37. Maxwell P.H., Winearls C.G. Recurrence of autonomous
hyperparathyroidism in dialysis patients. Nephrol. Dial.
Transplant. 1997; 12: 2195–2200.
38. 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.
39. 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.
40. Mizobuchi M., Ogata H., Hatamura I. et al. Activation of calcium-sensing receptor accelerates apoptosis in hyperplastic
parathyroid cells. Biochem. Biophys. Res. Commun. 2007;
362: 11–16.
41. 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.
42. Mucsi I., Hercz G. Adynamic bone disease: Pathogenesis,
diagnosis and clinical relevance. Curr. Opin. Nephrol.
Hypertens. 1997; 6: 356–361.
43. 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): 1–201.
44. Nemeth E.F., Steffey M.E., Hammerland LG. et al. Calcimimetics with potent and selective activity on the parathyroid
calcium receptor. Proc. Natl. Acad. Sci. U.S.A. 1998; 95:
4040–4045.
45. Neonakis E., Wheeler M.H., Krishnan H. et al. Results of surgical treatment of renal hyperparathyoidism. Arch. Surg.
1995; 130: 643–648.
46. 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.
47. 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.
48. O’Leary D.P., White H.J.O. Parathyroidectomy for hyperparathyroidism associated with renal disease. Ann. R. Coll.
Surg. Engl. 1995; 77: 97–101.
49. Ockert S., Willeke F., Richter A. et al. Total parathyroidectomy without autotransplantation as standard procedure in the
treatment of secondary hyperparathyroidism. Langenbecks
Arch. Surg. 2002; 387: 204–209.
50. Ogg C.S. Total parathyroidectomy in treatment of secondary
(renal) hyperparathyroidism. Br. Med. J. 1967; 4 (5575):
331–334.
51. Owda A., Elhwairis H., Narra S. et al. Secondary hyperparathyroidism in chronic hemodialysis patients: prevalence
and race. Ren. Fail. 2003; 25: 595–602.
52. 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-centre study. Clin. Drug. Investig. 2008; 28: 635–643.
53. Pasch A. Bone mass gain after parathyroidectomy. Kidney
Int. 2008; 74: 697–699.
54. 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.
55. Reichel H., Deibert B., Schmidt)Gayk H., Ritz E. Calcium
metabolism in early chronic renal failure: Implications for the
pathogenesis of hyperparathyroidism. Nephrol. Dial. Transplant. 1991; 6: 162–169.
56. Richards M.L. Wormuth J. Bingener J. Sirinek K. Parathyroidectomy in secondary hyperparathyroidism: Is there an optimal operative management? Surgery. 2006; 139 (2): 174–180.
57. Rodriguez M., Caravaca F., Fernandez E. et al. Parathyroid
function as a determinant of the response to calcitriol treatment in the hemodialysis patient. Kidney Int. 1999; 56:
306–317.
58. 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.
59. Schaefer R.M., Bover J., Dellanna F. et al. Efficacy of cinacalcet administered with the first meal after dialysis: the SENSOR Study. Clin. Nephrol. 2008; 70: 126–134.
60. Silver J., Naveh)Many T. Phosphate and the parathyroid.
Kidney Int. 2009; 75: 898–905.
61. Silver J., Naveh)Many T., Mayer H. et al. Regulation by vitamin D metabolites of parathyroid hormone gene transcription
in vivo in the rat. J. Clin. Invest. 1986; 78: 1296–1301.
62. 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.
63. Slatopolsky E., Delmez J. Pathogenesis of secondary hyperparathyroidism. Neprol. Dial. Transplant. 1996; 11, (3):
130–136.
64. 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.
65. Stehman)Breen C., Muirhead N., Thorning D., Sherrard D.
Secondary hyperparathyroidism complicated by parathyro=
matosis. Am. J. Kidney. Dis. 1996; 28: 502–507.
66. 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.
67. 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
68. 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.
69. Terawaki H., Nakano H., Takeguchi F. et al. Regression of
parathyroid gland swelling by treatment with cinacalcet.
Nephrol. Dial. Transplant. 2009; 24: 691–692.
70. Tominaga Y., Numano M., Tanaka Y. et al. Surgical Treatment
of Renal Hyperparathyroidism. Sem. Surg. Oncol. 1997; 13:
87–96.
71. Tominaga Y., Kazuaru U., Toshihito H. More than 1000 cases
of parathyroidectomy with forearm autograft for renal hyperparathyroidism. Am. J. Kidney. Dis. 2001; 38 Suppl: 168–171.
72. 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
73. 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.
74. Valderrabano F., Golper T., Muirhead N. et al. Chronic kidney
disease: why is current management uncoordinated and suboptimal? Nephrol. Dial. Transplant. 2001; 16: 61–64.
75. 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.
76. Yajima A., Inaba M., Tominaga Y., Ito A. Bone formation by
minimodeling is more active than remodeling after parathyroidectomy.Kidney Int. 2008; 74: 775–781.
77. 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.
78. 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,.
79. 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.
80. Zimmermann G., Neyer U., Haid A. et al. Erfahrungen mit der
totalen Parathyreoidektomie und Autotransplantation intraoperativ ausgewa. hlten Parathyreoidea=Gewebes beim reaktiven renalen Hyperparathyreoidismus. Wien. Klin. Wochenschr. 1992; 104: 434–438.
81. “Official Positions of the International Society for Clinical
Densitometry”, Corperight ISCD, October 2007, Supersedes
all prior “Official Positions” publications.

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

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

Keywords:
Secondary hyperparathyroidism, haemodialysis, parathyroidectomy, Mimpara (Cinacalcet HCl).