Магнийсодержащие фосфатбиндеры: новые терапевтические возможности при хронической болезни почек

Н.А. Михайлова

Кафедра нефрологии и гемодиализа ГБОУ ДПО РМАПО Минздрава России
Обсуждаются данные о гомеостазе магния (Mg) в организме человека, его взаимосвязь с заболеваемостью и смертностью в общей популяции и среди больных хронической болезнью почек (ХБП). Продемонстрирована эффективность магнийсодержащих фосфатбиндеров в отношении стабилизации показателей фосфорно-кальциевого обмена и торможения сосудистой кальцификации (СК) у больных ХБП.


  1. Weast R.C. Handbook of Chemistry and Physics. Boca Roton, FL: CRC Press, 1987.

  2. Elin R.J. Magnesium metabolism in health and disease. Dis Mon,1988;34:161–218.

  3. Aikawa J.K. Magnesium: Its biological significance. Boca Roton, FL: CRC Press, 1981.

  4. Fox C., Ramsoomair D., Carter C. Magnesium: its proven and potential clinical significance. South Med J, 2001; 94:1195–1201.

  5. Lewellen T.K., Nelp W.P., Murano R. et al. Absolute measurement of total-body calcium by the Ar-37 method-preliminary results: concise communication. J Nucl Med, 1977; 18:929–932.

  6. Rude R. Magnesium disorders. In: Kokko J, Tannen R (eds). Fluids and electrolytes. Philadeiphia PA: WB Sounders Company, 1996. P 421–445.

  7. Maguire M.E., Covan J.A. Magnesium chemistry and biochemistry. Biometals, 2002; 15:203–210.

  8. Touiz R.M. Magnesium in clinical medicine. Front Biosci, 2004; 9:1278–1293.

  9. Tietz N.W. Clinical guide to laboratory tests. Philadelphia PA, WB Sounders Company,1990.

  10. Avioli L.V., Berman M. Mg28 kinetics in man. J Appl Physiol, 1966; 21:1688–1694.

  11. Alfrey A.C., Miller N.L. Bone magnesium pools in uremia. J Clin Invest, 1973; 52:3019–3027.

  12. Rude R. Gruber H.E. Magnesium deficiency and osteoporosis: animal and human observations. J Nutr Biochem, 2004; 15:710–716.

  13. Swaminathan R. Magnesium metabolism and its disorders. Clin Biochem Rev, 2003; 24:47–66.

  14. Reis M.A., Reyes F.G., Saad M.G. et al. Magnesium deficiency modulates the insulin signaling pathway in liver but not muscleof rats. J Nutr, 2000; 130:133–138.

  15. Li F.Y., Chaigne-Delalande B., Kanellopoulou C. et al. Second messengerrole of Mg2+ revealed by human T-cell immunodeficiency. Nature, 2011; 475:471–476.

  16. Walser M. Magnesium metabolism. Ergeb Physiol, 1967; 59:185–296.

  17. Wacker W. Magnesium and man. Cambrige MA: Havard University Press, 1980; 1–184.

  18. Orrenius S., Zhivotovsky B., Nicotera P. Regulation of cell death: the calcium-apoptosis linc. Nat Rev Mol Cell Biol, 2003; 4:552–565.

  19. Hunter D.R., Haworth R.A., Southard J.H. Relationship between configuration, function and permeability in calcium-treated mitochondria. J Biol Chem, 1976; 251:5069–5077.

  20. Marx A., Neutra R.R. Magnesium in drinking water and ischemic heart disease. Epidemiol Rev, 1997; 19:258–272.

  21. Ford E.S., Mokdad A.H. Dietary Magnesium intake in a national sample of US adults. J Nutr, 2003; 133:2879–2882.

  22. Massry S.G., Seelig M.S. Hypomagnesiemia and hypermagnesiemia. Clin Nephrol, 1977; 7:147–153.

  23. Le Grimellec C. Micropuncture study along the proximal convoluted tubule. Electrolite reabsorbtion in first convolutions. Pflugers Arch, 1975; 354:133–150.

  24. Hou J., Renigunta H., Gomes A.S. et al. Claudin 16 and claudin 19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium. Proc Natl Acad Sci USA, 2009; 106:15350–15355.

  25. Nijenhuis T., Vallan V., van der Kemp A.W. et al. Enhanced passive Ca2+ reabsorption and and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. J Clin Invest, 2005; 115:1651–1658.

  26. Chertow B., Bamberger S., Stoico M. et al. Hypomagnesemia in patients in postoperative intensive care. Chest, 1989; 95:391–397.

  27. Whang R., Ryder K.W. Frequency of hypomagnesemia and hypermagnesemia. Requested vs rutine. JAMA, 1990;263:3063–3064.

  28. Hashizume N., Mari M. An analysis of hypermagnesemia and hypomagnesemia. Jpn J Med, 1990; 29:368–372.

  29. Danziger J., William J.H., Scott D.J. et al. Proton-pump inhibitor use is associated with low serum magnesium concentrations. Kidney International, 2013; 83, 692–699.

  30. Fung M.C., Weintraub M., Bowen D.L. Hypermagnesemia. Elderly over-the-counter drug users and risk. Arch Farm Med, 1995; 4:718–723.

  31. Ford E.S., Giles W.H., Dietz W.H. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA, 2002; 287:356–359.

  32. Guerro-Romera F., Rodriguez-Maran M. Low serum magnesium levels and metabolic syndrome. Acta Diabetol, 2002; 39:209–213.

  33. He K., Lui K., Daviglus M.L. et al. Magnesium intake and incidence of metabolic syndrome among young adults. Circulation, 2006; 113:1675–1682.

  34. Lopez-Ridaura R., Willett W.C., Rimm E.B. et al. Magnesium intake and risk type 2 diabetes in men and women. Diabetes Care, 2004;27:134–140.

  35. Song Y., Manson J.E., Buring J.E. et al. Dietary magnesium intake in relation to plasma insulinlevels and risk of type 2 diabetes in women. Diabetes Care, 2004;27:59–65.

  36. Pham P.C., Pham P.M., Pham P.A. et al. Lower serum magnesium levels are associated with more rapid decline of renal function in patients with diabetes mellitus type 2. Clin Nephrol, 2005; 63:429–436.

  37. Altura B.M., Altura B.T. New perspectives on the role of magnesium in the pathophysiology of the cardiovascular system. I Clin Aspects. Magnesium. 1985;4:226–244.

  38. Rodriguez-Maran M., Guerro-Romero F. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double blinde controlled trial. Diabetes Care, 2003; 26:1147–1152.

  39. Jee S.H., Miller E.R., Gualiar E. et al. The effect of the magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trial. Am J Hypertens, 2002; 15:691–696.

  40. Whang R., Chrysant S., Dillard B. et al. Hypomagnesemia and hypokalemia in 1000 treated ambulatory hypertensive patients. J Am Coll Nutr, 1982; 1:317–322.

  41. Ma J., Falsom A.R., Melnick S.L. et al. Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study. J Clin Epidemiol, 1995; 48:927–940.

  42. Johnson C.J., Peterson D.R., Smith E.K. Myocardial tissue concentrations of magnesium and potassium in men dying suddenly from ischemic heart disease. Am J Clin Nutr, 1979; 32:967–970.

  43. Antman E.M. Magnesium in acute myocardial infarction: overview of available evidence. Am Heart J, 1966; 132:487–495.

  44. Iseri L.T., French J.H. Magnesium: natere’s physiologic calcium blocker. Am Heart J, 1984; 108:188–193.

  45. Massry S.G. Magnesium homeostasis in patients with renal failure. Contrib Nephrol, 1984; 38:175–184.

  46. Navarro-Gonzalez J.F., Mora-Fernandez C., Garsia-Perez J. Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis. Semin Dial, 2009; 22:37–44.

  47. Zaman F., Abreo K. Severe hypermagnesemia as a result of laxative use in renal insufficiency. South Med J, 2003; 96:102–103.

  48. Mountokalakis T.D. Magnesium metabolism in chronic renal failure. Magnes Res, 1990; 3:121–127.

  49. Navarro J.F., Mora C., Jimenez A. et al. Relationship between serum magnesium and parathyroid hormonelevels in hemodialysis patients. Am J Kidney Dis, 1999; 34:43–48.

  50. Navarro J.F., Mora C., Macia M. et al. Serum magnesium concentration is an independent predictor of parathyroid hormone levels in peritoneal dialysis patients. Perit Dial Int, 1999; 19:455–461.

  51. Ferment O., Garnier P.E., Touitou Y. Comparison of the feedback effect of magnesium and calcium on parathyroid hormone secretion in man. J Endocrinol, 1987; 113:117–122.

  52. Miki H., Maercklein P.B., Fitzpatric L.A. Effect of magnesium on parathyroid cells: evidence for two sensing receptors or two intracellular pathways? Fm J Physiol, 1997; 272:E1–E6.

  53. Moriniere P., Vinatier I., Westeel P.F. et al. Magnesium hydroxide as a complementary aluminium-free phosphate binder to moderate dosesof oral calcium in uremic patients on chronic hemodialysis: lack of deleterious effect on bone mineralization. Nephrol Dial Transplant, 1988; 3:651–656.

  54. Broun J., Oldendorf M., Mashage W. et al. Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis, 1996;27:394–401.

  55. Nakamura S., Ishibashi-Ueda H., Nilzuma S. et al. Coronary calcification in patients with chronic kidney disease and coronary artery disease. Clin J Am Soc Nephrol, 2009; 4:1892–1900.

  56. Noordzij M., Cranenburg E.M., Engelsman L.F. et al. Progression of aortic calcification is associated with disorders of mineral metabolism and mortality in chronic dialysis patients. Nephrol Dial Transplant, 2011; 26:1662–1669.

  57. Temmar M., Liabeuf S., Renard C. et al. Pulse wave velocity and vascular calcification at different stages of chronic kidney disease. J Hypertens, 2010; 28:163–169.

  58. Speer M.Y., Giachelli C.M. Regulation of cardiovascular calcification. Cardiovasc Pathol, 2004; 13:63–70.

  59. Nikolov I.G., Mozar A., Drueke T.B. et al. Impact of disturbances of calcium and phosphate metabolism on vascular calcification and clinical outcomes in patients with chronic kidney disease. Blood Purif, 2009; 27:350–359.

  60. Shanahan C.M. Mechanisms of vascular calcification in renal disease. Clin Nephrol, 2005; 63:146–157.

  61. Giachelli C.M. The emerging role og phosphate in vascular calciphication. Kidney Int, 2009; 75:890–897.

  62. Shroff R.C., McNair R., Skepper J.N. et al. Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification. J Am Soc Nephrol, 2010; 21:103–112.

  63. Contiguglia S.R., Alfrey A.C., Miller N.L. et al. Nature of soft tissue calcification in uremia. Kidney Int, 1973; 4:229–235.

  64. Schlieper G., Aretz A., Verberckmoes S.C. et al. Ultrastructural analysis of vascular calcifications in uremia. J Am Soc Nephrol, 2010; 21:689–696.

  65. LeGeros R.Z. Formation and transformation of calcium phosphates: relevance to vascular calcification. Z Kardial, 2001; 90:III/116–III/124.

  66. Montezano A.C., Zimmerman D., Yusuf H. et al. Vascular smooth muscle cell differentiation to an osteogenic phenotype involves TRPM7 modulation by magnesium. Hypertention, 2010; 56:453–462.

  67. Louvet L., Büchel J., Steppan S. et al. Magnesium prevents phosphate-induced calcification in human aortic vascular smooth muscle cells. Nephrol Dial Transplant, 2013; 28: 869–878.

  68. Bennet R.M., Lehr J.R., McCarty D.J. Factors affecting the solubility of calcium pyrophosphate dehydrate crystals. J Clin Invest, 1975; 56:1571–1579.

  69. Smajilovic S., Hansen J.L., Cristoffersen T.E. et al. Extracellular calcium sensing in rat aoirtic vascular smooth muscle cells. Biochem Biophys Res Commun, 2006; 348:1215–1223.

  70. Gorgels T.G., Waarsing J.H., de Wolf A. et al. Dietary magnesium, not calcium, prevents vascular calcification in a mous model for pseudoxanthoma elasticum. J Mol Med, 2010; 88:467–475.

  71. Ishimura E., Okuno S., Kitatani K. et al. Significant association between the presence of peripheral vascular calcification and lower serum magnesium in hemodialysis patients. Clin Nephrol, 2007; 68:222–227.

  72. Turgut F., Kanbay M., Metin M.R. et al. Magnesium supplementation helps to improve carotid intima media thickness in patients on hemodialysis. Int Urol Nephrol, 2008; 40:1075–1082.

  73. Ishimura E, Okuno S, Yamakawa T et al. Serum magnesium concentration is a significant predictor of mortality in maintenance hemodialysis patients. Magnes Res, 2007; 20:237–244.

  74. Lacson E., Wang W., Lazarus M. et al. Magnesium and mortality risk in hemodialysis patients. ASN Renal Week 27 Oct – 1 Nov, 2009, San-Diego, CF, USA, Poster F-PO1488.

  75. Marczell B., Arcossy O., Gurevich K., Kaufmann P. Association of serum magnesium with mortality – results from a large European database. ERA-EDTA Congress, Prague, 26 June, 2011, Abstract Su0008.

  76. Chertow G.M., Raggi P., McCarthy J.T. et al. The effect of sevelamer and calcium acetate on proxies of atherosclerotic and arteriosclerotic vascular disease in hemodialysis patients. Am J Nephrol, 2003; 23:307–314.

  77. Hutchison A.J. Oral phosphate binders. Kidney Int, 2009; 75:906–914.

  78. Guillot A.P., Hood V.L., Runge C.F. et al. The use of magnesium-containing phosphate binders in patients with end-stage renal disease on maintenance hemodialysis. Nephron, 1982; 30:114–117.

  79. Delmez J.A., Kelber J., Norword K.Y. et al. Magnesium carbonate as a phosphate binder: a prospective, controlled, crossover study. Kidney Int, 1996; 49:163–167.

  80. Spiegel D.M., Farmar B., Smits G. et al. Magnesium carbonate is an effective phosphate binder for chronic hemodialysis patients: a pilot study. J Ren Nutr, 2007; 17:416–422.

  81. Parsons V., Baldwin D., Moniz C. et al. Successful control of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis using magnesium carbonate and calcium carbonate as phosphate binders. Nephron, 1993; 63:379–383.

  82. De Francisco A.L., Leidig M., Covic A.C. et al. Evaluation of calcium acetate/magnesium carbonate as a phosphate binder compared with sevelamer hydrochloride in hemodialysis patients: a controlled, randomized study (CALMAG study) assessing efficacy and tolerability. Nephrol Dial Transplant, 2010; 25:3707–3717.

  83. McIntyre C.W., Pai P., Warwick G. et al. Iron-magnesium hydroxycarbonate (fermagate): a novel non-calcium-containing phosphate binderfor the treatment of hyperphosphatemia in chronic hemodialysis patients. Clin J Am Soc Nephrol, 2009; 4:401–409.

  84. Kircelli F., Peter M.E., Sevinc O.E. et al. Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner. Nephrol Dial Transplant, 2011; 27:514–521.

  85. Li Q., Larusso J., Grand-Pierre A.E. et al. Magnesium carbonate containing phosphate binder prevents connective tissue mineralization in Abcc6(-/-) mice – potential for treatment of pseudoxantoma elasticum. Clin Transl Sci, 2009; 2:398–404.

  86. De Shutter T.M., Behets G.J., Geryl H. et al. Effect of magnesium-based phosphate binder on medial calcification in rat model of uremia. Kidney Int, 2013; 83:1109–1117.

  87. Chertow G.M., Burke S.K., Dillon M.A. et al. Long-term effects of sevelamer hydrochlorid on the calcium x phosphate product and lipid profile, soluble CD14 and endotoxin levels in hemodialysis patients.

Об авторах / Для корреспонденции

Михайлова Н.А. – доцент кафедры нефрологии и гемодиализа
ГБОУ ДПО РМАПО Минздрава России, к.м.н.

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