nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-14Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESПатогенез нарушений обмена фосфатов при хронической болезни почек: все ли так ясно, как кажется?Pathogenesis of phosphate exchange disorders in CKD: is all as clear as seems to be?ДобронравовВ. А.DobronravovV. A.dobronravov@nephrolog.ruБогдановаЕ. О.BogdanovaE. O.noemail@neicon.ruНаучно-исследовательский институт нефрологии Первого Санкт-Петербургского государственного медицинского университета им. акад. И.П. ПавловаRussian Federation2014010320141824246Copyright © Добронравов В.А., Богданова Е.О., 20142014Добронравов В.А., Богданова Е.О.Dobronravov V.A., Bogdanova E.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/14

Проанализированы современные представления о развитии и прогрессировании нарушений обмена фосфатов при ХБП, основанные на новых данных о патофизиологии и молекулярных механизмах взаимодействия фосфат-регулирующих систем.

Modern concepts on the development and progression of phosphate exchange disorders at CKD, based on the novel data on pathophysiology and molecular mechanisms of phosphate-regulating systems interactions are reviewed.

фактор роста фибробластов 23паратиреоидный гормонвторичный гиперпаратиреозэкспериментальное моделированиехроническое повреждение почекхроническая болезнь почекнеорганический фосфатмочевая экскрецияαKlothoαKlothofibroblast growth factor 23parathyroid hormonesecondary hyperparathyroidismexperimental modelingchronic kidney injurychronic kidney diseaseinorganic phosphateurinary excretionReferencesKestenbaum В, Sampson JN, Rudser KD. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 2005;16(2):520-528Kestenbaum В, Sampson JN, Rudser KD. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 2005;16(2):520-528Levin A, Bakris GL, Molitch M et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 2007;71(1):31-38Levin A, Bakris GL, Molitch M et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 2007;71(1):31-38Fang X, Ginsberg C, Sugatani T et al. Early chronic kidney disease-mineral bone disorder stimulates vascular calcification. Kidney Int 2014;85(1):142-150Fang X, Ginsberg C, Sugatani T et al. Early chronic kidney disease-mineral bone disorder stimulates vascular calcification. Kidney Int 2014;85(1):142-150Portale AA, Halloran BP, Murphy MM et al. Oral intake of phosphorus can determine the serum concentration of 1,25-di-hydroxyvitamin D by determining its production rate in humans. J Clin Invest 1986;77(1):7-12Portale AA, Halloran BP, Murphy MM et al. Oral intake of phosphorus can determine the serum concentration of 1,25-di-hydroxyvitamin D by determining its production rate in humans. J Clin Invest 1986;77(1):7-12Slatopolsky E. The intact nephron hypothesis: the concept and its implications for phosphate management in CKD-related mineral and bone disorder. Kidney Int 2011;79:3-8Slatopolsky E. The intact nephron hypothesis: the concept and its implications for phosphate management in CKD-related mineral and bone disorder. Kidney Int 2011;79:3-8Denda M, Finch J, Slatopolsky E. Phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure. Am J Kidney Dis 1996;28(4):596-602Denda M, Finch J, Slatopolsky E. Phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure. Am J Kidney Dis 1996;28(4):596-602Martin DR, Ritter CS, Slatopolsky E et al. Acute regulation of parathyroid hormone by dietary phosphate. Am J Physiol Endocrinol Metab 2005;289(4):729-734Martin DR, Ritter CS, Slatopolsky E et al. Acute regulation of parathyroid hormone by dietary phosphate. Am J Physiol Endocrinol Metab 2005;289(4):729-734Hsu CY, Chertow GM. Elevations of serum phosphorus and potassium in mild to moderate chronic renal insufficiency. Nephrol Dial Transplant 2002 Aug;17(8):1419-1425Hsu CY, Chertow GM. Elevations of serum phosphorus and potassium in mild to moderate chronic renal insufficiency. Nephrol Dial Transplant 2002 Aug;17(8):1419-1425Murayama A, Takeyama K, Kitanaka S et al. Positive and negative regulations of the renal 25-hydroxyvitamin D3 1alpha-hydroxylase gene by parathyroid hormone, calcitonin, and 1alpha,25(OH)2D3 in intact animals. Endocrinology. 1999;140(5):2224-2231Murayama A, Takeyama K, Kitanaka S et al. Positive and negative regulations of the renal 25-hydroxyvitamin D3 1alpha-hydroxylase gene by parathyroid hormone, calcitonin, and 1alpha,25(OH)2D3 in intact animals. Endocrinology. 1999;140(5):2224-2231Hasegawa H, Nagano N, Urakawa I et al. Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease. Kidney Int 2010;78:975-980Hasegawa H, Nagano N, Urakawa I et al. Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease. Kidney Int 2010;78:975-980Prié D, Friedlander G. Reciprocal control of 1,25-dihydroxyvitamin D and FGF23 formation involving the FGF23/ Klotho system. Clin J Am Soc Nephrol 2010;5(9):1717-1722Prié D, Friedlander G. Reciprocal control of 1,25-dihydroxyvitamin D and FGF23 formation involving the FGF23/ Klotho system. Clin J Am Soc Nephrol 2010;5(9):1717-1722Andrukhova O, Zeitz U, Goetz R et al. FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1/2-SGK1 signaling pathway. Bone 2012;51(3):621-628Andrukhova O, Zeitz U, Goetz R et al. FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1/2-SGK1 signaling pathway. Bone 2012;51(3):621-628Добронравов ВА. Современный взгляд на патофизиологию вторичного гиперпаратиреоза: роль фактора роста фибробластов 23 и Klotho. Нефрология 2011; 15(4): 11-20Добронравов ВА. Современный взгляд на патофизиологию вторичного гиперпаратиреоза: роль фактора роста фибробластов 23 и Klotho. Нефрология 2011; 15(4): 11-20Hu MC, Kuro-o M, Moe OW. Klotho and chronic kidney disease. Contrib Nephrol 2013;180:47-63Hu MC, Kuro-o M, Moe OW. Klotho and chronic kidney disease. Contrib Nephrol 2013;180:47-63Urakawa I, Yamazaki X, Shimada T et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 2006; 444(7120):770-774Urakawa I, Yamazaki X, Shimada T et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 2006; 444(7120):770-774Martin A, David V, Quarles LD. Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev 2012;92(1):131-155Martin A, David V, Quarles LD. Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev 2012;92(1):131-155Kuro-o М. Phosphate and Klotho. Kidney International 2011;79 (Suppl 121):20-23Kuro-o М. Phosphate and Klotho. Kidney International 2011;79 (Suppl 121):20-23Cha SK, Ortega B, Kurosu H et al. Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1. Proc NatlAcad Sci U S A 2008;105(28):9805-9810Cha SK, Ortega B, Kurosu H et al. Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1. Proc NatlAcad Sci U S A 2008;105(28):9805-9810Drüeke T. Klotho, FGF23, and FGF receptors in chronic kidney disease: a yin-yang situation? Kidney Int 2010;78(11):1057-1060Drüeke T. Klotho, FGF23, and FGF receptors in chronic kidney disease: a yin-yang situation? Kidney Int 2010;78(11):1057-1060Imura A, Tsuji X, Murata M et al. alpha-Klotho as a regulator of calcium homeostasis. Science 2007;316(5831):1615-1618Imura A, Tsuji X, Murata M et al. alpha-Klotho as a regulator of calcium homeostasis. Science 2007;316(5831):1615-1618Hu MC, Shi M, Zhang J et al. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J 2010;24(9):3438-3450Hu MC, Shi M, Zhang J et al. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J 2010;24(9):3438-3450Isakova T, Wahl P, Vargas GS et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 2011;79(12):1370-1378Isakova T, Wahl P, Vargas GS et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 2011;79(12):1370-1378Pavik I, Jaeger P, Ebner L. Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrol Dial Transplant 2013;28(2):352-359Pavik I, Jaeger P, Ebner L. Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrol Dial Transplant 2013;28(2):352-359Aizawa H, Saito X Nakamura T et al. Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats. Biochem Biophys Res Commun 1998;249:865-871Aizawa H, Saito X Nakamura T et al. Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats. Biochem Biophys Res Commun 1998;249:865-871Haruna X Kashihara N, Satoh M et al. Amelioration of progressive renal injury by genetic manipulation of Klotho gene. Proc Natl Acad Sci USA 2007; 104: 2331-2336Haruna X Kashihara N, Satoh M et al. Amelioration of progressive renal injury by genetic manipulation of Klotho gene. Proc Natl Acad Sci USA 2007; 104: 2331-2336Wang Y, Sun Z. Klotho gene delivery prevents the progression of spontaneous hypertension and renal damage. Hypertension 2009; 54:810-817Wang Y, Sun Z. Klotho gene delivery prevents the progression of spontaneous hypertension and renal damage. Hypertension 2009; 54:810-817Asai O, Nakatani K, Tanaka T et al. Decreased renal alpha-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion. Kidney Int 2012;81:539-547Asai O, Nakatani K, Tanaka T et al. Decreased renal alpha-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion. Kidney Int 2012;81:539-547Fliser D, Kollerits B, Never U et al. Fibroblast growth factor 23 (FGF-23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. JAm Soc Nephrol 2007; 18 (9): 2600-2608Fliser D, Kollerits B, Never U et al. Fibroblast growth factor 23 (FGF-23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. JAm Soc Nephrol 2007; 18 (9): 2600-2608Titan SM, Zatz R, Graciolli FG et al. FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol 2010; 6 (2): 241-247Titan SM, Zatz R, Graciolli FG et al. FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol 2010; 6 (2): 241-247Gutierrez OM, Mannstadt M, Isakova T et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008; 359 (6): 584-592Gutierrez OM, Mannstadt M, Isakova T et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008; 359 (6): 584-592Hu MC, Shi M, Zhang J et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 2011; 22 (1): 124-136Hu MC, Shi M, Zhang J et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 2011; 22 (1): 124-136Vervloet M, Larsson T. Fibroblast growth factor-23 and Klotho in chronic kidney disease. Kidney Int 2011; Suppl. 1: 130135Vervloet M, Larsson T. Fibroblast growth factor-23 and Klotho in chronic kidney disease. Kidney Int 2011; Suppl. 1: 130135Mirza MA, Larsson A, Lind L et al. Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 2009; 205 (2): 385-390Mirza MA, Larsson A, Lind L et al. Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 2009; 205 (2): 385-390Mirza MA, Hansen T, Johansson L et al. Relationship between circulating FGF-23 and total body atherosclerosis in the community. Nephrol Dial Transplant 2009; 24 (10): 3125-3131Mirza MA, Hansen T, Johansson L et al. Relationship between circulating FGF-23 and total body atherosclerosis in the community. Nephrol Dial Transplant 2009; 24 (10): 3125-3131Yilmaz MI, Sonmez A, Saglam M et al. FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease. Kidney Int 2010; 78 (7): 679-685Yilmaz MI, Sonmez A, Saglam M et al. FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease. Kidney Int 2010; 78 (7): 679-685Kirkpantur A, Balci M, Gurbuz CA et al. Serum fibroblast growth factor-23 (FGF-23) levels are independently associated with left ventricular mass and myocardial performance index in maintenance haemodialysis patients. Nephrol Dial Transplant 2011; 26 (4): 1346-1354Kirkpantur A, Balci M, Gurbuz CA et al. Serum fibroblast growth factor-23 (FGF-23) levels are independently associated with left ventricular mass and myocardial performance index in maintenance haemodialysis patients. Nephrol Dial Transplant 2011; 26 (4): 1346-1354Kusaba T, Okigawa M, Matui A et al. Klotho is associated with VEGF receptor-2 and the transient receptor potential canoni-cal-1 Ca channel to maintain endothelial integrity. Proc NatlAcad Sci USA 2010; 107 (45): 19308-19313Kusaba T, Okigawa M, Matui A et al. Klotho is associated with VEGF receptor-2 and the transient receptor potential canoni-cal-1 Ca channel to maintain endothelial integrity. Proc NatlAcad Sci USA 2010; 107 (45): 19308-19313Nagai R, Saito X Ohyama Y et al. Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases. Cell Mol Life Sci 2000; 57 (5): 738-746Nagai R, Saito X Ohyama Y et al. Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases. Cell Mol Life Sci 2000; 57 (5): 738-746Sakan H, Nakatani K, Asai O et al. Reduced Renal α-Klotho Expression in CKD Patients and Its Effect on Renal Phosphate Handling and Vitamin D Metabolism. PLoS One 2014;9(1):e86301Sakan H, Nakatani K, Asai O et al. Reduced Renal α-Klotho Expression in CKD Patients and Its Effect on Renal Phosphate Handling and Vitamin D Metabolism. PLoS One 2014;9(1):e86301Gutierrez O, Isakova T, Rhee E et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005;16:2205-2215Gutierrez O, Isakova T, Rhee E et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005;16:2205-2215Prié D, Friedlander G. Reciprocal control of 1,25-dihydroxyvitamin D and FGF23 formation involving the FGF23/ Klotho system. Clin J Am Soc Nephrol 2010;5(9):1717-1722Prié D, Friedlander G. Reciprocal control of 1,25-dihydroxyvitamin D and FGF23 formation involving the FGF23/ Klotho system. Clin J Am Soc Nephrol 2010;5(9):1717-1722Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int 2012;82(7):737-747Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int 2012;82(7):737-747Isakova T, Gutierrez O, Shah A. Postprandial mineral metabolism and secondary hyperparathyroidism in early CKD. J Am Soc Nephrol 2008;19(3):615-623Isakova T, Gutierrez O, Shah A. Postprandial mineral metabolism and secondary hyperparathyroidism in early CKD. J Am Soc Nephrol 2008;19(3):615-623Haussler MR, Whitfield GK, Kaneko I et al. The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis. Rev Endocr Metab Disord 2012;13(1):57-69.Haussler MR, Whitfield GK, Kaneko I et al. The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis. Rev Endocr Metab Disord 2012;13(1):57-69.Kido S, Kaneko I, Tatsumi S et al.Vitamin D and type II sodium-dependent phosphate cotransporters. Contrib Nephrol 2013;180:86-97Kido S, Kaneko I, Tatsumi S et al.Vitamin D and type II sodium-dependent phosphate cotransporters. Contrib Nephrol 2013;180:86-97Biber J, Hernando N, Forster I. Phosphate transporters and their function. Annu Rev Physiol 2013;75:535-550Biber J, Hernando N, Forster I. Phosphate transporters and their function. Annu Rev Physiol 2013;75:535-550Sitara D. Correlation among hyperphosphatemia, type II sodium phosphate transporter activity, and vitamin D metabolism in Fgf-23 null mice. Ann N YAcad Sci 2007;1116:485-493Sitara D. Correlation among hyperphosphatemia, type II sodium phosphate transporter activity, and vitamin D metabolism in Fgf-23 null mice. Ann N YAcad Sci 2007;1116:485-493Rowe PS. Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway. Crit Rev Eukaryot Gene Expr 2012;22(1):61-86Rowe PS. Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway. Crit Rev Eukaryot Gene Expr 2012;22(1):61-86Quarles LD. «FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization.» Am J Physiol Endocrinol Metab 2003;285(1):1-9Quarles LD. «FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization.» Am J Physiol Endocrinol Metab 2003;285(1):1-9Villa-Bellosta R, Ravera S, Sorribas V et al. The Na+-Pi cotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary Pi. Am J Physiol Renal Physiol 2009;296:691-699Villa-Bellosta R, Ravera S, Sorribas V et al. The Na+-Pi cotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary Pi. Am J Physiol Renal Physiol 2009;296:691-699Добронравов ВА, Богданова ЕО, Семенова НЮ, и др. Почечная экспрессия белка αKlotho, фактор роста фибробластовДобронравов ВА, Богданова ЕО, Семенова НЮ, и др. Почечная экспрессия белка αKlotho, фактор роста фибробластови паратиреоидный гормон при экспериментальном моделировании ранних стадий хронического повреждения почек. Нефрология 2014; 18(2): 42-45и паратиреоидный гормон при экспериментальном моделировании ранних стадий хронического повреждения почек. Нефрология 2014; 18(2): 42-45

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