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El factor de crecimiento fibroblástico 23 (FGF-23) es una hormona derivada del hueso que participa en la regulación de la homeostasis del fósforo. Los niveles de FGF-23 se encuentran extremamente elevados en la enfermedad renal crónica y existe evidencia del papel de esta hormona en la patogénesis de los trastornos óseos y minerales en esta situación. Más aún, datos recientes implican al FGF-23 en la patogénesis de otras complicaciones sistémicas asociadas a las alteraciones óseo-minerales de la enfermedad renal crónica. La evidencia creciente de que las alteraciones del metabolismo mineral no se limitan a la enfermedad ósea ha acentuado el interés por la patofisiología y el tratamiento de las alteraciones del metabolismo mineral en la enfermedad renal crónica. Se ha propuesto que el aumento de FGF-23 es la respuesta inicial en los estadios precoces de la enfermedad renal crónica a la necesidad de proteger al organismo de los efectos adversos de la retención de fósforo. Estos aumentos de FGF-23 se asocian al riesgo creciente de mortalidad cardiovascular en los enfermos renales crónicos y son mediadores directos de toxicidad cardíaca. En esta revisión procuramos presentar aspectos relevantes de la fisiología del FGF-23 en la biología ósea y en la homeostasis mineral, así como en la fisiopatología de la enfermedad renal crónica y sus implicaciones clínicas.
Palabras clave:
TMO-ERC
Palabras clave:
Metabolismo óseo
Palabras clave:
FGF-23
Palabras clave:
Metabolismo óseo-mineral
Palabras clave:
Enfermedad renal crónica (ERC)
Fibroblast Growth Factor 23 (FGF-23) is a bone-derived hormone involved in the regulation of phosphate homeostasis. FGF-23 levels are extremely elevated in Chronic Kidney Disease (CKD) and there is evidence supporting the role of this hormone in the pathogenesis of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Furthermore, recent data associates FGF-23 with the pathogenesis of systemic complications of CKD-MBD. The increasing evidence that the consequences of abnormal mineral metabolism are not restricted to bone disease changed the approach to the pathophysiology and treatment of disturbed bone and mineral metabolism in CKD patients. FGF-23 has been proposed to be the initial adaptive response in early CKD to protect the organism from the adverse effects of phosphate retention. Increased levels of FGF-23 observed in CKD patients are associated with cardiovascular mortality risk and was shown to mediate direct, "off-target" toxicity to the heart. This report aims to review the relevant aspects of the physiology of FGF-23 in bone biology and mineral homeostasis and the role of FGF-23 in the pathophysiology of CKD-BMD and its clinical implications.
Keywords:
CKD-MBD
Keywords:
Bone metabolism
Keywords:
FGF-23
Keywords:
Mineral and bone metabolism
Keywords:
Chronic kidney disease (CKD)
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Bibliografía
[1]
Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int 2012;82(7):737-47. [Pubmed]
[2]
Fukagawa M, Akizawa T. Calcium abnormalities of dialysis patients. J Bone Miner Metab 2006;24(2):160. [Pubmed]
[3]
Shimada T, Muto T, Urakawa I, Yoneya T, Yamazaki Y, Okawa K, et al. Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo. Endocrinology 2002;143(8):3179-82. [Pubmed]
[4]
Larsson T, Nisbeth U, Ljunggren O, Juppner H, Jonsson KB. Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int 2003;64(6):2272-9. [Pubmed]
[5]
Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006;69(11):1945-53.
[6]
Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, Xie H, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 2011;79(12):1370-8. [Pubmed]
[7]
Canziani ME, Tomiyama C, Higa A, Draibe SA, Carvalho AB. Fibroblast growth factor 23 in chronic kidney disease: bridging the gap between bone mineral metabolism and left ventricular hypertrophy. Blood Purif 2011;31(1-3):26-32. [Pubmed]
[8]
Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A, et al. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol 2007;18(9):2600-8. [Pubmed]
[9]
Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, et al. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 2011;305(23):2432-9. [Pubmed]
[10]
Wesseling-Perry K, Jüppner H. The osteocyte in CKD: New concepts regarding the role of FGF23 in mineral metabolism and systemic complications. Bone 2012;54(2):222-9. [Pubmed]
[11]
Mac Way F, Lessard M, Lafage-Proust MH. Pathophysiology of chronic kidney disease-mineral and bone disorder. Joint Bone Spine 2012;79(6):544-9. [Pubmed]
[12]
Bargman J, Skorecki, K. In: Longo D, Fauci, A (eds.). Harrison's Principles of Internal Medicine, Chap. 280. 18th Edition ed. United States of America: Mc-Graw Hill; 2012.
[13]
Liu S, Zhou J, Tang W, Jiang X, Rowe DW, Quarles LD. Pathogenic role of Fgf23 in Hyp mice. Am J Physiol Endocrinol Metab 2006;291(1):E38-49. [Pubmed]
[14]
Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 2004;19(3):429-35. [Pubmed]
[15]
Cozzolino M, Mazzaferro S. The fibroblast growth factor 23: a new player in the field of cardiovascular, bone and renal disease. Curr Vasc Pharmacol 2010;8(3):404-11. [Pubmed]
[16]
Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, et al. Human fibroblast growth factor-23 mutants suppress Na -dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production. J Biol Chem 2003;278(4):2206-11. [Pubmed]
[17]
Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M, et al. The parathyroid is a target organ for FGF23 in rats. J Clin Invest 2007;117(12):4003-8. [Pubmed]
[18]
Bhattacharyya N, Chong WH, Gafni RI, Collins MT. Fibroblast growth factor 23: state of the field and future directions. Trends Endocrinol Metab 2012;23(12):610-8. [Pubmed]
[19]
Topaz O, Shurman DL, Bergman R, Indelman M, Ratajczak P, Mizrachi M, et al. Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat Genet 2004;36(6):579-81. [Pubmed]
[20]
Li H, Martin A, David V, Quarles LD. Compound deletion of Fgfr3 and Fgfr4 partially rescues the Hyp mouse phenotype. Am J Physiol Endocrinol Metab 2011;300(3):E508-17. [Pubmed]
[21]
Donate-Correa J, Mora-Fernández C, Martínez-Sanz R, Muros-de-Fuentes M, Pérez H, Meneses-Perez B, et al. Expression of FGF23/KLOTHO system in human vascular tissue. Int J Cardiol 2013;165(1):179-83. [Pubmed]
[22]
Lindberg K, Olauson H, Amin R, Ponnusamy A, Goetz R, Taylor RF, et al. Arterial klotho expression and FGF23 effects on vascular calcification and function. PloS One 2013;8(4):e60658. [Pubmed]
[23]
Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997;390(6655):45-51. [Pubmed]
[24]
Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, et al. Suppression of aging in mice by the hormone Klotho. Science 2005;309(5742):1829-33. [Pubmed]
[25]
Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 2006;444(7120):770-4. [Pubmed]
[26]
Shalhoub V, Ward SC, Sun B, Stevens J, Renshaw L, Hawkins N, et al. Fibroblast growth factor 23 (FGF23) and alpha-klotho stimulate osteoblastic MC3T3.E1 cell proliferation and inhibit mineralization. Calcif Tissue Int 2011;89(2):140-50. [Pubmed]
[27]
Marsell R, Krajisnik T, Goransson H, Ohlsson C, Ljunggren O, Larsson TE, et al. Gene expression analysis of kidneys from transgenic mice expressing fibroblast growth factor-23. Nephrol Dial Transplant 2008;23(3):827-33. [Pubmed]
[28]
Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y. Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol 2003;17(12):2393-403. [Pubmed]
[29]
Smith RC, O'Bryan LM, Farrow EG, Summers LJ, Clinkenbeard EL, Roberts JL, et al. Circulating alphaKlotho influences phosphate handling by controlling FGF23 production. J Clin Invest 2012;122(12):4710-5. [Pubmed]
[30]
Juppner H, Wolf M. alphaKlotho: FGF23 coreceptor and FGF23-regulating hormone. J Clin Invest 2012;122(12):4336-9. [Pubmed]
[31]
Koh N, Fujimori T, Nishiguchi S, Tamori A, Shiomi S, Nakatani T, et al. Severely reduced production of klotho in human chronic renal failure kidney. Biochem Biophys Res Commun 2001;280(4):1015-20. [Pubmed]
[32]
Donate-Correa J, Muros-de-Fuentes M, Mora-Fernández C, Navarro-González JF. FGF23/Klotho axis: phosphorus, mineral metabolism and beyond. Cytokine Growth Factor Rev 2012;23(1-2):37-46. [Pubmed]
[33]
Liu S, Rowe PS, Vierthaler L, Zhou J, Quarles LD. Phosphorylated acidic serine-aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity. J Endocrinol 2007;192(1):261-7. [Pubmed]
[34]
Sato T, Tominaga Y, Ueki T, Goto N, Matsuoka S, Katayama A, et al. Total parathyroidectomy reduces elevated circulating fibroblast growth factor 23 in advanced secondary hyperparathyroidism. Am J Kidney Dis 2004;44(3):481-7. [Pubmed]
[35]
Wang H, Yoshiko Y, Yamamoto R, Minamizaki T, Kozai K, Tanne K, et al. Overexpression of fibroblast growth factor 23 suppresses osteoblast differentiation and matrix mineralization in vitro. J Bone Miner Res 2008;23(6):939-48. [Pubmed]
[36]
Sitara D, Razzaque MS, Hesse M, Yoganathan S, Taguchi T, Erben RG, et al. Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol 2004;23(7):421-32. [Pubmed]
[37]
Liu S, Tang W, Fang J, Ren J, Li H, Xiao Z, et al. Novel regulators of Fgf23 expression and mineralization in Hyp bone. Mol Endocrinol 2009;23(9):1505-18. [Pubmed]
[38]
Stubbs JR, Liu S, Tang W, Zhou J, Wang Y, Yao X, et al. Role of hyperphosphatemia and 1,25-dihydroxyvitamin D in vascular calcification and mortality in fibroblastic growth factor 23 null mice. J Am Soc Nephrol 2007;18(7):2116-24.
[39]
Sitara D, Kim S, Razzaque MS, Bergwitz C, Taguchi T, Schuler C, et al. Genetic evidence of serum phosphate-independent functions of FGF-23 on bone. PLoS Genet 2008;4(8):e1000154. [Pubmed]
[40]
Liu S, Guo R, Simpson LG, Xiao ZS, Burnham CE, Quarles LD. Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX. J Biol Chem 2003;278(39):37419-26. [Pubmed]
[41]
Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, et al. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet 2006;38(11):1310-5. [Pubmed]
[42]
Martin A, Liu S, David V, Li H, Karydis A, Feng JQ, et al. Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling. FASEB J 2011;25(8):2551-62. [Pubmed]
[43]
Ichikawa S, Baujat G, Seyahi A, Garoufali AG, Imel EA, Padgett LR, et al. Clinical variability of familial tumoral calcinosis caused by novel GALNT3 mutations. Am J Med Genet A 2010;152A(4):896-903. [Pubmed]
[44]
Goetz R, Nakada Y, Hu MC, Kurosu H, Wang L, Nakatani T, et al. Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation. Proc Natl Acad Sci U S A 2010;107(1):407-12. [Pubmed]
[45]
Raimann A, Ertl DA, Helmreich M, Sagmeister S, Egerbacher M, Haeusler G. Fibroblast growth factor 23 and Klotho are present in the growth plate. Connect Tissue Res 2013;54(2):108-17. [Pubmed]
[46]
Samadfam R, Richard C, Nguyen-Yamamoto L, Bolivar I, Goltzman D. Bone formation regulates circulating concentrations of fibroblast growth factor 23. Endocrinology 2009;150(11):4835-45. [Pubmed]
[47]
Wesseling-Perry K, Pereira RC, Wang H, Elashoff RM, Sahney S, Gales B, et al. Relationship between plasma fibroblast growth factor-23 concentration and bone mineralization in children with renal failure on peritoneal dialysis. J Clin Endocrinol Metab 2009;94(2):511-7. [Pubmed]
[48]
Antoniucci DM, Yamashita T, Portale AA. Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men. J Clin Endocrinol Metab 2006;91(8):3144-9. [Pubmed]
[49]
Gutierrez OM, Wolf M, Taylor EN. Fibroblast growth factor 23, cardiovascular disease risk factors, and phosphorus intake in the health professionals follow-up study. Clin J Am Soc Nephrol 2011;6(12):2871-8. [Pubmed]
[50]
Wesseling-Perry K, Pereira RC, Sahney S, Gales B, Wang HJ, Elashoff R, et al. Calcitriol and doxercalciferol are equivalent in controlling bone turnover, suppressing parathyroid hormone, and increasing fibroblast growth factor-23 in secondary hyperparathyroidism. Kidney Int 2011;79(1):112-9. [Pubmed]
[51]
Ito N, Fukumoto S, Takeuchi Y, Takeda S, Suzuki H, Yamashita T, et al. Effect of acute changes of serum phosphate on fibroblast growth factor (FGF)23 levels in humans. J Bone Miner Metab 2007;25(6):419-22. [Pubmed]
[52]
Mirams M, Robinson BG, Mason RS, Nelson AE. Bone as a source of FGF23: regulation by phosphate? Bone 2004;35(5):1192-9. [Pubmed]
[53]
Liu S, Tang W, Zhou J, Stubbs JR, Luo Q, Pi M, et al. Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol 2006;17(5):1305-15. [Pubmed]
[54]
Barthel TK, Mathern DR, Whitfield GK, Haussler CA, Hopper HAt, Hsieh JC, et al. 1,25-Dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism. J Steroid Biochem Mol Biol 2007;103(3-5):381-8.
[55]
Ohnishi M, Nakatani T, Lanske B, Razzaque MS. Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1alpha-hydroxylase. Kidney Int 2009;75(11):1166-72. [Pubmed]
[56]
Shimada T, Yamazaki Y, Takahashi M, Hasegawa H, Urakawa I, Oshima T, et al. Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism. Am J Physiol Renal Physiol 2005;289(5):F1088-95. [Pubmed]
[57]
Lavi-Moshayoff V, Wasserman G, Meir T, Silver J, Naveh-Many T. PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol 2010;299(4):F882-9. [Pubmed]
[58]
López I, Rodríguez-Ortiz ME, Almadén Y, Guerrero F, de Oca AM, Pineda C, et al. Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo. Kidney Int 2011;80(5):475-82. [Pubmed]
[59]
Gupta A, Winer K, Econs MJ, Marx SJ, Collins MT. FGF-23 is elevated by chronic hyperphosphatemia. J Clin Endocrinol Metab 2004;89(9):4489-92. [Pubmed]
[60]
Geller JL, Khosravi A, Kelly MH, Riminucci M, Adams JS, Collins MT. Cinacalcet in the management of tumor-induced osteomalacia. J Bone Miner Res 2007;22(6):931-7. [Pubmed]
[61]
Finch JL, Tokumoto M, Nakamura H, Yao W, Shahnazari M, Lane N, et al. Effect of paricalcitol and cinacalcet on serum phosphate, FGF-23, and bone in rats with chronic kidney disease. Am J Physiol Renal Physiol 2010;298(6):F1315-22.
[62]
Yilmaz MI, Sonmez A, Saglam M, Yaman H, Kilic S, Eyileten T, et al. Comparison of calcium acetate and sevelamer on vascular function and fibroblast growth factor 23 in CKD patients: a randomized clinical trial. Am J Kidney Dis 2012;59(2):177-85. [Pubmed]
[63]
Singh RJ, Kumar R. Fibroblast growth factor 23 concentrations in humoral hypercalcemia of malignancy and hyperparathyroidism. Mayo Clin Proc 2003;78(7):826-9. [Pubmed]
[64]
Rodriguez-Ortiz ME, Lopez I, Munoz-Castaneda JR, Martinez-Moreno JM, Ramirez AP, Pineda C, et al. Calcium deficiency reduces circulating levels of FGF23. J Am Soc Nephrol 2012;23(7):1190-7. [Pubmed]
[65]
Rodríguez M, López I, Muñoz J, Aguilera-Tejero E, Almadén Y. FGF23 and mineral metabolism, implications in CKD-MBD. Nefrologia 2012;32(3):275-8.
[66]
Schouten BJ, Hunt PJ, Livesey JH, Frampton CM, Soule SG. FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study. J Clin Endocrinol Metab 2009;94(7):2332-7. [Pubmed]
[67]
Schouten BJ, Doogue MP, Soule SG, Hunt PJ. Iron polymaltose-induced FGF23 elevation complicated by hypophosphataemic osteomalacia. Ann Clin Biochem 2009;46(Pt 2):167-9. [Pubmed]
[68]
Shimizu Y, Tada Y, Yamauchi M, Okamoto T, Suzuki H, Ito N, et al. Hypophosphatemia induced by intravenous administration of saccharated ferric oxide: another form of FGF23-related hypophosphatemia. Bone 2009;45(4):814-6. [Pubmed]
[69]
Takeda Y, Komaba H, Goto S, Fujii H, Umezu M, Hasegawa H, et al. Effect of intravenous saccharated ferric oxide on serum FGF23 and mineral metabolism in hemodialysis patients. Am J Nephrol 2011;33(5):421-6. [Pubmed]
[70]
Deger SM, Erten Y, Pasaoglu OT, Derici UB, Reis KA, Onec K, et al. The effects of iron on FGF23-mediated Ca-P metabolism in CKD patients. Clin Exp Nephrol 2013;17(3):416-23. [Pubmed]
[71]
Imel EA, Peacock M, Gray AK, Padgett LR, Hui SL, Econs MJ. Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. J Clin Endocrinol Metab 2011;96(11):3541-9. [Pubmed]
[72]
Farrow EG, Yu X, Summers LJ, Davis SI, Fleet JC, Allen MR, et al. Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. Proc Natl Acad Sci U S A 2011;108(46):E1146-55. [Pubmed]
[73]
ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 2000;26(3):345-8. [Pubmed]
[74]
Bhattacharyya N, Wiench M, Dumitrescu C, Connolly BM, Bugge TH, Patel HV, et al. Mechanism of FGF23 processing in fibrous dysplasia. J Bone Miner Res 2012;27(5):1132-41. [Pubmed]
[75]
Gutierrez O, Isakova T, Rhee E, Shah A, Holmes J, Collerone G, et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005;16(7):2205-15. [Pubmed]
[76]
Wolf M. Forging forward with 10 burning questions on FGF23 in kidney disease. J Am Soc Nephrol 2010;21(9):1427-35. [Pubmed]
[77]
Pereira RC, Juppner H, Azucena-Serrano CE, Yadin O, Salusky IB, Wesseling-Perry K. Patterns of FGF-23, DMP1, and MEPE expression in patients with chronic kidney disease. Bone 2009;45(6):1161-8. [Pubmed]
[78]
Sabbagh Y, Graciolli FG, O'Brien S, Tang W, dos Reis LM, Ryan S, et al. Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy. J Bone Miner Res 2012;27(8):1757-72. [Pubmed]
[79]
Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, 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):31-8.
[80]
Quarles LD. Role of FGF23 in vitamin D and phosphate metabolism: implications in chronic kidney disease. Exp Cell Res 2012;318(9):1040-8. [Pubmed]
[81]
Komaba H, Goto S, Fujii H, Hamada Y, Kobayashi A, Shibuya K, et al. Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. Kidney Int 2010;77(3):232-8. [Pubmed]
[82]
Galitzer H, Ben-Dov IZ, Silver J, Naveh-Many T. Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease. Kidney Int 2010;77(3):211-8. [Pubmed]
[83]
Gogusev J, Duchambon P, Hory B, Giovannini M, Goureau Y, Sarfati E, et al. Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 1997;51(1):328-36. [Pubmed]
[84]
Brown AJ, Dusso A, Lopez-Hilker S, Lewis-Finch J, Grooms P, Slatopolsky E. 1,25-(OH)2D receptors are decreased in parathyroid glands from chronically uremic dogs. Kidney Int 1989;35(1):19-23.
[85]
Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008;359(6):584-92. [Pubmed]
[86]
Mirza MA, Larsson A, Lind L, Larsson TE. Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 2009;205(2):385-90. [Pubmed]
[87]
Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest 2011;121(11):4393-408. [Pubmed]
[88]
Gross ML, Ritz E. Hypertrophy and fibrosis in the cardiomyopathy of uremia--beyond coronary heart disease. Semin Dial 2008;21(4):308-18. [Pubmed]
[89]
Shastri S, Tangri N, Tighiouart H, Beck GJ, Vlagopoulos P, Ornt D, et al. Predictors of sudden cardiac death: a competing risk approach in the hemodialysis study. Clin J Am Soc Nephrol 2012;7(1):123-30. [Pubmed]
[90]
Hu MC, Shi M, Zhang J, Quinones H, Griffith C, Kuro-o M, et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 2011;22(1):124-36. [Pubmed]
[91]
Wetmore JB, Liu S, Krebill R, Menard R, Quarles LD. Effects of cinacalcet and concurrent low-dose vitamin D on FGF23 levels in ESRD. Clin J Am Soc Nephrol 2010;5(1):110-6. [Pubmed]
[92]
Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K. Association of activated vitamin D treatment and mortality in chronic kidney disease. Arch Intern Med 2008;168(4):397-403. [Pubmed]
