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Том 6 №2 2004 год - Нефрология и диализ

Вторичный гиперпаратиреоз при хронической почечной недостаточности. Лечение активными метаболитами витамина D


Волгина Г.В.

Аннотация: За последнее десятилетие существенно изменилось понимание патофизиологических процессов, ведущих к развитию вторичного гиперпаратиреоза (ВГПТ) у больных с хронической почечной недостаточностью (ХПН). Вторичный гиперпаратиреоз является частым и грозным осложнением ХПН и развивается в результате относительного или абсолютного дефицита кальцитриола (КТ) и нарушения гомеостаза кальция и фосфора

Для цитирования: Волгина Г.В. Вторичный гиперпаратиреоз при хронической почечной недостаточности. Лечение активными метаболитами витамина D. Нефрология и диализ. 2004. 6(2):116-126. doi:


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Ключевые слова: хроническая почечная недостаточность, фосфорно-кальциевый гомеостаз, гиперпаратиреоз, витамин D

Список литературы:
  1. Ермоленко В.М. Нарушение фосфорно-кальциевого обмена. Нефрология. Руководство для врачей. 2000: 62-75.
  2. Розен В.Б. Основы эндокринологии. М.: МГУ, 1994: 384.
  3. Akizawa T., Fukagawa H., Koshikawa S., Kurosawa K. Recent progress in management secondary hyperparathyroidism of chronic renal failure. Curr Opin Hypertens 1993; 2: 558-565.
  4. Alexiewicz J.M., Klinger M., Pitt S.M. et al. PTH inhibits B cell proliferation: implication in chronic renal failure. J Am Soc Nephrol 1990; 1: 236-244.
  5. Amann K., Ritz E., Wiest G., Klaus G., Mall G. A role of parathyroid hormone for activation of cardiac fibroblast in uremia. J Amer Soc Nephrol 1994; 4 (10): 1814-1819.
  6. Arnold A., Brown M.F., Urena P., Gaz R.D., Sarfati E., Drueke T.B. Monoclonality of parathyroid tumors in chronic renal failure and in primary parathyroid hyperplasia. J Clin Invest 1995; 95: 2047-2053.
  7. Bacchini G., Fabrizi F., Pontoriero G., Marcelli D., Filippo S.D., Locatelli F. «Pulse oral» versus intravenous calcitriol therapy in chronic hemodialysis patients: a prospective and randomized study. Nephron 1997; 77: 267-272. [Erratum, Nephron 1998; 79: 509].
  8. Block G.A., Hulberi-Shearon T.E., Levin N.W., Port F.K. Association of serum phosphorus and calcium[-phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998; 4: 607-617.
  9. 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.
  10. Brown A.J., Ritter C., Fineh J., Slatopolsky E. Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: role of dietary phosphate. Kidney Int 1999; 55: 1284-1292.
  11. Brown E.M., Pollak M., Riccardi D., Hebert S.C. Cloning and characterization of an extracellular Ca-sensing receptor from parathyroid and kidney: new insights into the physiology and pathophysiology of calcium metabolism. Nephrol Dial Transplant 1994; 9: 1703-1706.
  12. Brown E.M., Pollak M., Seidma M.C. et al. Calcium-Ion-Sensing Cell-Surface Receptors. N Engl J Med 1995; 333: 234-240.
  13. Brown E.M., Gamba G., Riccardi D. et al. Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid. Nature 1993; 366: 575-580.
  14. Brown E.M., Vassilev P.M., Quinn S., Hebert S.C. G-protein-coupled, extracellular Ca2+-sensing receptor: a versatile regulator of diverse cellular functions. Vitam Horm 1999; 55: 1-71.
  15. Cannata Andia J.B. Adynamic bone and chronic renal failure: an overview. Am J Med Sci 2000; 320: 81-84.
  16. Cholst I.N., Steinberg S.F., Tropper P.J. et al. The influence of hypermagnesemia on serum calcium and parathyroid hormone in human subjects. N Engl J Med 1984; 310: 1221-1225.
  17. Chorev M., Alexander J.M., Rosenblatt M. Interactions of parathyroid hormone and parathyroid homone-related protein with their receptors. In: Bilezikian J.P., Levine M.A., Marcus R. eds. The parathyroids: basic and clinical concepts. 2nd ed. San Diego, Calif.: Academic Press (in press).
  18. Chung U., Igarashi T., Nishishita T. et al. The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium. J Biol Chem 1996; 271: 8593-8598.
  19. Combe C., Aparicio M. Phosphorus and protein restriction and parathyroid function in chronic renal failure. Kidney Int 1994; 46: 1381-1386.
  20. Demay M.B., Kiernan M.S., DeLuca H.F., Kronenberg H.M. Sequences in the human parathyroid hormone gene that bind the 1,25-dihydroxyvitamin D3 receptor and mediate transcriptional repression in response to 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A 1992; 89: 8097-8101.
  21. Edwards R.M. Disorders of posphat metabolism in chronic renal disease. Curr Opin Pharmacol 2002; 2: 171-176.
  22. Ellis R.E., Juan J., Horwitz H.R. Mechanism and function of cell death. Ann Rev Cell Biol 1991; 7: 663-698.
  23. Falchetti A., Pale A.F., Amorosi A. Progression of uremic hyperparathyroidism involves alleic loss on chromosome 11. J Endocrinol Metab 1993; 76: 139-144.
  24. Feinfeld D.A., Sherwood L.M. Parathyroid hormone and 1,25(OH)2D3 in chronic renal failure. Kidney Int 1988; 33: 1048-1058.
  25. Fukagawa M. Cell biology of parathyroid hyperplasia in uremia. Am J Med Sci 1999; 317: 377-382.
  26. Fukagawa M. Resistance of parathyroid cell to calcitriol as a cause of parathyroid hyperfunction in chronic renal failure. Nephrol Dial Transplant 1995; 2: 316-319.
  27. Fukagawa M., Ji M., Kurokawa K. Calcitriol-induce apoptosis of hyperplastic parathyroid cells in uremic rats. J Am Soc Nephrol 1991; 2: 635 (abstract).
  28. Fukuda N., Tanaka H., Tominaga Y., Fukagawa M., Kurokawa K., Seino Y. Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. J Clin Invest 1993; 92: 1436-1443.
  29. Ganesh S.K., Stack A.G., Levin N.W., Hulbert-Shearon T., Port F.K. Association of elevated serum PO4, Ca x PO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001; 12: 2131-2138.
  30. Gogusev H., Duchambon P., Hory B. еt al. Depressed expression of calcium receptor in parathyroid gland tissue of patient with hyperparathyroidism. Kidney Int 1997; 51: 328-336.
  31. Goodman W.G., Goldin J., Kuizon B.D. et al. Coronary artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342: 1478-1483.
  32. Goodman W.G. Recent developments in the management of secondary hyperparathyroidism. Kidney Int 2001; 59: 1187-1201.
  33. Hasnain M., Hauncher C., Pegoraro A.A., Arruda J.A.L., Dunea G. Suppression of hyperparathyroidism by calcitriol therapy. ASAIO J 1999; 45: 424-427.
  34. Hayakawa Y., Tanaka Y., Funahashi H. et al. Hyperphosphatemia accelerates parathyroid cell proliferation and parathyroid hormone secretion in severe secondary parathyroid hyperplasia. Endocr J 1999; 46: 681-686.
  35. Hercz G., Pei G., Greenwood C. еt al. Aplastic osteodistrophy without aluminium. The role of «supressed» parathyroid function. Kidney Int 1993; 44: 860-866.
  36. Herrmann P., Ritz E., Schmidt-Gayk H. et al. Comparison of intermittent and continuous oral administration of calcitriol in dialysis patients; a randomized prospective trial. Nephron 1994; 67: 48-53.
  37. Horandner H.H., Neyer U., Gruber U. et al. Pathomorphology of parathyroid autografts. Nieren Hochdruckkrankheiten 1997; 26: 319-327.
  38. Hsu C.H. Are we mismanaging calcium and phosphate metabolism in renal failure? Am J Kidney Dis 1997; 29: 641-649.
  39. Indridason O.S., Quarles L.D. Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Kidney Int 2000; 57: 282-292.
  40. Islam A., Smogerzewski M., Massry S.G. Effect of verapamil of CRF-induced abnormalities in phospholipid contents of brain synaptosomes. Proc Soc Exp Biol Med 1990; 194: 16-20.
  41. Juppner H. Receptors for parathyroid hormone and parathyroid hormone-related peptide: exploration of their biological importance. Bone 1999; 25: 87-90.
  42. Juppner H., Abou Samra A., Freeman M. A G-proteinlinked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science 1991; 254: 1024-1026.
  43. Kifor O., Moore F.D., Wang P. еt al. Reduced immunostandartaining for the extracellular Ca-sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab 1996; 81: 1598-1606.
  44. Klin M., Smogorzewski M., Ni Z. еt al. Abnormalites in hepatic lipase in chronic renal failure: role of excess parathyroid hormone. J Clin Invest 1996; 97: 2167-2173.
  45. Kurdawa K. The kidney and calcium homeostasis. Kidney Int 1994; 45 (suppl 44): 97-105.
  46. Kuro-oM, Matsumura Y., Aizawa H. еt al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997; 390: 45-57.
  47. Li Y.C., Amling M., Pirro A.E. et al. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. Endocrinology 1998; 139: 4391-4396.
  48. Llach F., Massry S.G., Singer F.R. Skeletal resistence of endogenus PTH in patients with early renal failure. A possible cause of secondary hyperparathyroidism. J Clin Endocrinol Metab 1975; 44: 1054-1058.
  49. Llach F. Hyperphosphatemia in end-stage renal disease patients: pathophysiological consequences. Kidney Int 1999; 73 (Suppl): 31-37.
  50. Locatelli F., Cannata-Andia J.B., Drueke T.B. et al. Management of disturbances of calcium and phosphate metabolism in chronic renal insufficiency, with emphasis on the control of hyperphosphataemia. Nephrol Dial Transplant 2002; 17: 723-731.
  51. Loghman-Adham M. Phosphate binders for control of phosphate retention in chronic renal failure. Pediatr Nephrol 1999; 13: 701-708.
  52. Lopex-Hilker S., Dusso A.S., Rapp N.S. et al. Phosphorus restriction reverses secondary hyperparathyroidism independent of changes in Ca2+ and calcitriol. Am J Physiol 1990; 259: 432-437.
  53. Marchese A., George S.R., Kolakowski L.F., Lynch K.R., O’Dowd B.F. Novel GPCRs and their endogenous ligands: expanding the boundaries of physiology and pharmacology. Trends Pharmacol Sci 1999; 20: 370-375. [Erratum, Trends Pharmacol Sci 1999; 20: 447.]
  54. Marchais S.J., Metivier F., Guerin A., London G. Association of hyperphosphatemia with haemodynamic disturbances in end-stage renal disease. Nephrol Dial Transplant 1999; 14: 2178-2183.
  55. Massry S.G. Is parathyroid hormone a uremic toxin? Nephron 1977; 19: 125-130.
  56. Massry S.G. The toxic effect of parathyroid hormone in uremia. Semin Nephrol 1983; 3: 306-328.
  57. Massry S.G., Smogorzewski M. Mechanism through which PTH mediates its deleterious effects on organ function in uremia. Semin Nephrol 1994; 14: 219-231.
  58. Maung H.M., Elangovan L., Frazao J.M. et al. Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1alpha-hydroxyvitamin D2) in dialysis patients with secondary hyperparathyroidism: a sequential comparison. Am J Kidney Dis 2001; 37: 532-543.
  59. McCarron D.A., Lenfesty B., Narasimhan N., Barry J.M., Vetto R.M., Bennett WM. Anatomical heterogeneity of parathyroid glands in posttransplant hyperparathyroidism. Am J Nephrol 1988; 8: 388-391.
  60. McCarron D.A., Muther R.S., Lenfesty B., Bennett W.M. Parathyroid function in persistent hyperparathyroidism: relationship to gland size. Kidney Int 1982; 22: 662-670.
  61. Moallem E., Kilav R., Silver J., Naveh-Many T. RNA-protein binding and post-transcriptional regulation of parathyroid hormone gene expression by calcium and phosphate. J Biol Chem 1998; 273: 5253-5259.
  62. Mucsi I., Hercz G. Relative hypoparathyroidism and adynamic bone disease. Am J Med Sci 1999; 317: 405-409.
  63. Malluche H.H., Monier-Faugere M.C. Understanding and managing hyperphosphatemia in patients with chronic renal disease. Clin Nephrol 1999; 52: 267-277.
  64. Naveh-Many T., Rahamimov R., Livni N., Silver J. Parathyroid cell proliferation in normal and chronic renal failure rats: the effects of calcium, phosphate, and vitamin D. J Clin Invest 1995; 96: 1786-1793.
  65. Naveh-Many T., Marx R., Keshet E. et al. Regulation of 1,25(OH)2D3 receptor gene expression by 1,25(OH)2D3 in the parathyreoid in vivo. J Clin Invest 86: 1990; 1968-1975.
  66. Nygren P., Larsson S., Rastad J., Akerstrom G. 1,25(OH)2D3 inhibits hormone secretion and proliferation but not functional differentiation of cultured bovine parathiroid cells. Calcif Tissue Int 1988; 12: 213-218.
  67. Owda A., Elhwairis H., Narra S., Towery H., Osama S. Secondary hyperparathyroidism in chronic hemodialysis patients: prevalence and race. Ren Fail 2003; 25: 595-602.
  68. Parfitt A.M. The hyperparathyroidism of chronic renal failure: a disorder of growth. Kidney Int 1997; 52: 3-9.
  69. Patel S.R., Ke H.Q. Regulation of calcitriol receptors and its mRNA in normal and renal failure rats. Kidney Int 1994; 45: 1020-1027.
  70. Portale A.A., Halloran B.P., Morris R.C. Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D3 by phosphoreus in normal men. J Clin Invest 1989; 83: 1494-1499.
  71. Raggi P., Boulay A., Chasan-Taber S. et al. Cardiac calcification in adult hemodialysis patients: a link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol 2002; 39: 695-701.
  72. Raine A.E.G., Bedford L., Simpson A.W.M. et al. Hyperparathyroidism, platelet intracellular free calcium and hypertension in CRF. Kidney Int 1993; 43: 700-705.
  73. Reichel H., Drucke T.B., Ritz E. Oxford textbook of clinical nephrology. Second edition. Oxford university press 1998; 1954-1981: 2808.
  74. Ribeiro S., Ramos A., Brandao A. et al. Cardiac valve calcification in haemodialysis patients: role of calcium-phosphate metabolism. Nephrol Dial Transplant 1998; 13: 2037-2040.
  75. Ritz E., Kuster S., Schmidt-Gayk H. et al. Low-dose calcitriol prevents the rise in 1,84-iPTH without affecting serum calcium and phosphate in patients with moderate renal failure (prospective placebo controlled multicentre trial). Nephrol Dial Transplant 1995; 10: 2228-2234.
  76. Ritz E., Stefanski A., Rambausek M. The role of the parathyroid glands in the uremic syndrome. Am J Kidney Dis 1995; 26 (5): 808-813.
  77. Qing D.P., Ding H., Vadgama J. et al. Elevate myocardial cytosolic calcium impairs insulin-like growth factor-1 stimulated protein syntesis in CRF. J Am Soc Nephrol 1999; 10: 84-92.
  78. Salem M.M. Hyperparathyroidism in the hemodialysis population: a survey of 612 patients. Am J Kidney Dis 1997; 29: 862-865.
  79. Salusky I.B., Goodman W.G. Cardiovascular calcification in end-stage renal disease. Nephrol Dial Transplant 2002; 17: 336-339.
  80. Schomig M., Ritz E. Management of distrurbed calcium metabolism in uremic patients: use of vitamin D metabolites. Nephrol Dial Transplant 2000; 15 (suppl 5): 18-24.
  81. Sherrard D.J., Hercz G., Pei Y. et al. The spectrum of bone disease in end-stage renal failure - an evolving disorder. Kidney Int 1993; 43: 436-442.
  82. Silver J., Kilav R., Naveh-Many T. Mechanisms of secondary hyperparathyroidism. Am J Physiol 2002; 283: 367-376.
  83. Silver J., Naweh-Many T., Mayer H. et al. Regulation by vitamin D metabolites of parathyroid gene transcription in vivo in rat. J Clin Invest 1986; 78: 1296-1301.
  84. Silver J., Russel J., Sherwood L.M. Regulation by vitamin D metabolites of mRNA for preproparathyroid hormon in isolated bovine parathyroid cells. Proc Nate Acad Sci 1985; 82: 4270-4273.
  85. Slatopolsky E., Brown A., Dusso A. Pathogenesis of secondary hyperparathyroidism. Kidney Int Suppl 1999; 73: S14-S19.
  86. Slatopolsky E., Brown A., Dusso A. Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 2002; 37: 54-57.
  87. Slatopolsky E., Finch J., Denda M. et al. Phosphorus restriction prevents parathyroid gland growth: high phosphorus directly stimulates PTH secretion in vivo. J Clin Invest 1996; 97: 2534-2540.
  88. Smogorzewski M. PTH, chronic renal failure and myocardium. Miner Electrol Metab 1995; 21: 55-62.
  89. Smogorzewski M., Koureta P., Fadda G. et al. Chronic parathyroid hormone excess in vivo increases resting levels of cytosolic calcium in brain synaptosomes: studies in the presence and absence of chronic renal failure. L Amer Soc Nephrol 1991; 1: 1162-1168.
  90. Solal M.-E.C., Sebert J.-L., Boudailliez B. et al. Comparison of intact, midregion, and carboxy terminal assays of parathyroid hormone for the diagnosis of bone disease in hemodialyzed patients. J Clin Endocrinol Metab 1991; 73: 516-524.
  91. Strewler G.J. The physiology of parathyroid hormone-related protein. N Engl J Med 2000; 342: 177-185.
  92. Thenmin N., Smogorzewski M., Massry S.G. Derangements in acetylcholine metabolism in brain synaptosomes in CRF. Kidney Int 1993; 44: 630-637.
  93. Thomas L., Clemens P.D. Cardiovascular biology of the parathyroid hormone-related proteins. Endocrinology of cardiovascular function. Ed. By Ellis R., Levin A., Terry L. Kluwer Academic Publishers. Boston (Dordrecht) London: 1998: 237-254.
  94. Tian J., Smogorzewski M., Kedes L., Massry S.G. PTH - PTHrP receptors mRNA in downregulated in chronic renal failure. Am J Nephrol 1994; 14: 41-46.
  95. Tominaga Y., Kohara S., Namii Y. et al. Clonal analysis of nodular hyperplasia in renal hyperparathyroidism. World J Surg 1996; 20: 744-752.
  96. Tominaga Y., Tanaka Y., Sato K., Nagasaka T., Takagi H. Histology, pathophysiology, and indications for surgical treatment of renal hyperparathyroidism. Semin Surg Oncol 1997; 13: 78-86.
  97. Usdin T.B., Hoare S.R.J., Wang T., Mezey E., Kowalak J.A. TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus. Nat Neurosci 1999; 2: 941-943.
  98. Van der Wielen R.P., Lowik M.R., van den Berg H. еt al. Serum vitamin D concentrations among elderly people in Europe. Lancet 1995; 346: 207-210.
  99. Wang R., Karpinski E., Pang P.K. Parathyroid hormone selectively inhibits L-type calcium channels in single vascular smooth muscle cells of the rat. J Physiol 1991; 441: 325-346.
  100. Weisinger J.R., Fafus M.J., Langman C.B. et al. Regulation of 1,25-dihydroxyvitamin D3 by calcium in the parathyroidectomized parathyroid hormone - replete rat. J Bone Miner Res 1989; 4: 929-935.
  101. Yoshida T., Fujimori T., Nabeshima Y. Mediation of unusually high concentrations of 1,25-dihydroxyvitami D in homozygous klotho mutant mice by incression of renal 1alpha-hydroxylase gene. Endocrinology 2002; 13: 683-689.

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