Pediatric Nephrology

, Volume 28, Issue 11, pp 2089–2096

From bone abnormalities to mineral metabolism dysregulation in autosomal dominant polycystic kidney disease

Review

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of kidney failure. It is a systemic disorder, not only affecting the kidneys, but also associated with cyst formation in other organs such as the liver, spleen, pancreas, and seminal vesicles. Other extra-renal symptoms may consist of intracranial arterial aneurysms, cardiac valvular defects, abdominal and inguinal hernias and colonic diverticulosis. Very little is known regarding bone involvement in ADPKD; however, recent evidence has revealed the potential role of fibroblast growth factor 23 (FGF23). FGF23 is an endocrine fibroblast growth factor acting in the kidney as a phosphaturic hormone and a suppressor of active vitamin D with key effects on the bone/kidney/parathyroid axis, and has been shown to increase in patients with ADPKD, even with normal renal function. The aim of this review is to provide an overview of bone and mineral abnormalities found in experimental models and in patients with ADPKD, and to discuss the possible role of FGF23 in this disease.

Keywords

ADPKD FGF23 Bone Primary cilia 

Abbreviations

ADPKD

Autosomal dominant polycystic kidney disease

[Ca2+]cyt

Cytosolic Ca2+ concentration

CKD

Chronic kidney disease

1,25(OH)2D

1,25-dihydroxyvitamin D

FGF23

Fibroblast growth factor 23

GFR

Glomerular filtration rate

PC1

Polycystin-1

PC2

Polycystin-2

TmP/GFR

Tubular maximum for phosphate corrected for the glomerular filtration rate

References

  1. 1.
    Gabow PA (1993) Autosomal dominant polycystic kidney disease. N Engl J Med 329:332–342PubMedCrossRefGoogle Scholar
  2. 2.
    Harris PC, Torres VE (2009) Polycystic kidney disease. Annu Rev Med 60:321–337PubMedCrossRefGoogle Scholar
  3. 3.
    Torres VE, Harris PC (2009) Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 76:149–168PubMedCrossRefGoogle Scholar
  4. 4.
    Wolf M (2012) Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int 82:737–747PubMedCrossRefGoogle Scholar
  5. 5.
    Pavik I, Jaeger P, Kistler AD, Poster D, Krauer F, Cavelti-Weder C, Rentsch KM, Wuthrich RP, Serra AL (2011) Patients with autosomal dominant polycystic kidney disease have elevated fibroblast growth factor 23 levels and a renal leak of phosphate. Kidney Int 79:234–240PubMedCrossRefGoogle Scholar
  6. 6.
    Pavik I, Jaeger P, Ebner L, Poster D, Krauer F, Kistler AD, Rentsch K, Andreisek G, Wagner CA, Devuyst O, Wuthrich RP, Schmid C, Serra AL (2012) Soluble klotho and autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 7:248–257PubMedCrossRefGoogle Scholar
  7. 7.
    Cheong B, Muthupillai R, Rubin MF, Flamm SD (2007) Normal values for renal length and volume as measured by magnetic resonance imaging. Clin J Am Soc Nephrol 2:38–45PubMedCrossRefGoogle Scholar
  8. 8.
    Chapman AB, Schrier RW (1991) Pathogenesis of hypertension in autosomal dominant polycystic kidney disease. Semin Nephrol 11:653–660PubMedGoogle Scholar
  9. 9.
    Chapman AB, Johnson AM, Rainguet S, Hossack K, Gabow P, Schrier RW (1997) Left ventricular hypertrophy in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 8:1292–1297PubMedGoogle Scholar
  10. 10.
    Sedman A, Bell P, Manco-Johnson M, Schrier R, Warady BA, Heard EO, Butler-Simon N, Gabow P (1987) Autosomal dominant polycystic kidney disease in childhood: a longitudinal study. Kidney Int 31:1000–1005PubMedCrossRefGoogle Scholar
  11. 11.
    Schrier RW (2009) Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 20:1888–1893PubMedCrossRefGoogle Scholar
  12. 12.
    Gabow PA, Chapman AB, Johnson AM, Tangel DJ, Duley IT, Kaehny WD, Manco-Johnson M, Schrier RW (1990) Renal structure and hypertension in autosomal dominant polycystic kidney disease. Kidney Int 38:1177–1180PubMedCrossRefGoogle Scholar
  13. 13.
    Kelleher CL, McFann KK, Johnson AM, Schrier RW (2004) Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population. Am J Hypertens 17:1029–1034PubMedCrossRefGoogle Scholar
  14. 14.
    Fick GM, Johnson AM, Hammond WS, Gabow PA (1995) Causes of death in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 5:2048–2056PubMedGoogle Scholar
  15. 15.
    Torres VE, Donovan KA, Scicli G, Holley KE, Thibodeau SN, Carretero OA, Inagami T, McAteer JA, Johnson CM (1992) Synthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease. Kidney Int 42:364–373PubMedCrossRefGoogle Scholar
  16. 16.
    Loghman-Adham M, Soto CE, Inagami T, Cassis L (2004) The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol Ren Physiol 287:F775–F788CrossRefGoogle Scholar
  17. 17.
    Gabow PA (1990) Autosomal dominant polycystic kidney disease–more than a renal disease. Am J Kidney Dis 16:403–413PubMedGoogle Scholar
  18. 18.
    Bae KT, Zhu F, Chapman AB, Torres VE, Grantham JJ, Guay-Woodford LM, Baumgarten DA, King BF Jr, Wetzel LH, Kenney PJ, Brummer ME, Bennett WM, Klahr S, Meyers CM, Zhang X, Thompson PA, Miller JP (2006) Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort. Clin J Am Soc Nephrol 1:64–69PubMedCrossRefGoogle Scholar
  19. 19.
    Grantham JJ (2008) Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med 359:1477–1485PubMedCrossRefGoogle Scholar
  20. 20.
    Brun M, Maugey-Laulom B, Eurin D, Didier F, Avni EF (2004) Prenatal sonographic patterns in autosomal dominant polycystic kidney disease: a multicenter study. Ultrasound Obstet Gynecol 24:55–61PubMedCrossRefGoogle Scholar
  21. 21.
    Fick-Brosnahan G, Johnson AM, Strain JD, Gabow PA (1999) Renal asymmetry in children with autosomal dominant polycystic kidney disease. Am J Kidney Dis 34:639–645PubMedCrossRefGoogle Scholar
  22. 22.
    Schrier RW, Johnson AM, McFann K, Chapman AB (2003) The role of parental hypertension in the frequency and age of diagnosis of hypertension in offspring with autosomal-dominant polycystic kidney disease. Kidney Int 64:1792–1799PubMedCrossRefGoogle Scholar
  23. 23.
    Rizk D, Chapman A (2008) Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD. Pediatr Nephrol 23:1029–1036PubMedCrossRefGoogle Scholar
  24. 24.
    Sharp C, Johnson A, Gabow P (1998) Factors relating to urinary protein excretion in children with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 9:1908–1914PubMedGoogle Scholar
  25. 25.
    Mekahli D, Woolf AS, Bockenhauer D (2010) Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms. Pediatr Nephrol 25:2275–2282PubMedCrossRefGoogle Scholar
  26. 26.
    Selistre L, de Souza V, Ranchin B, Hadj-Aissa A, Cochat P, Dubourg L (2012) Early renal abnormalities in children with postnatally diagnosed autosomal dominant polycystic kidney disease. Pediatr Nephrol 27:1589–1593PubMedCrossRefGoogle Scholar
  27. 27.
    Bergmann C, Bruchle NO, Frank V, Rehder H, Zerres K (2008) Perinatal deaths in a family with autosomal dominant polycystic kidney disease and a PKD2 mutation. N Engl J Med 359:318–319PubMedCrossRefGoogle Scholar
  28. 28.
    Michaud EJ, Yoder BK (2006) The primary cilium in cell signaling and cancer. Cancer Res 66:6463–6467PubMedCrossRefGoogle Scholar
  29. 29.
    Praetorius HA, Spring KR (2005) A physiological view of the primary cilium. Annu Rev Physiol 67:515–529PubMedCrossRefGoogle Scholar
  30. 30.
    Ou G, Blacque OE, Snow JJ, Leroux MR, Scholey JM (2005) Functional coordination of intraflagellar transport motors. Nature 436:583–587PubMedCrossRefGoogle Scholar
  31. 31.
    Qin H, Burnette DT, Bae YK, Forscher P, Barr MM, Rosenbaum JL (2005) Intraflagellar transport is required for the vectorial movement of TRPV channels in the ciliary membrane. Curr Biol 15:1695–1699PubMedCrossRefGoogle Scholar
  32. 32.
    Rohatgi R, Snell WJ (2010) The ciliary membrane. Curr Opin Cell Biol 22:541–546PubMedCrossRefGoogle Scholar
  33. 33.
    Hu Q, Milenkovic L, Jin H, Scott MP, Nachury MV, Spiliotis ET, Nelson WJ (2010) A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution. Science 329:436–439PubMedCrossRefGoogle Scholar
  34. 34.
    Goetz SC, Anderson KV (2010) The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 11:331–344PubMedCrossRefGoogle Scholar
  35. 35.
    Wang X, Ward CJ, Harris PC, Torres VE (2010) Cyclic nucleotide signaling in polycystic kidney disease. Kidney Int 77:129–140PubMedCrossRefGoogle Scholar
  36. 36.
    Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33:129–137PubMedCrossRefGoogle Scholar
  37. 37.
    Praetorius HA, Spring KR (2003) The renal cell primary cilium functions as a flow sensor. Curr Opin Nephrol Hypertens 12:517–520PubMedCrossRefGoogle Scholar
  38. 38.
    Praetorius HA, Spring KR (2001) Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 184:71–79PubMedCrossRefGoogle Scholar
  39. 39.
    Xiao ZS, Quarles LD (2010) Role of the polycytin-primary cilia complex in bone development and mechanosensing. Ann N Y Acad Sci 1192:410–421PubMedCrossRefGoogle Scholar
  40. 40.
    AbouAlaiwi WA, Takahashi M, Mell BR, Jones TJ, Ratnam S, Kolb RJ, Nauli SM (2009) Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades. Circ Res 104:860–869PubMedCrossRefGoogle Scholar
  41. 41.
    Nauli SM, Kawanabe Y, Kaminski JJ, Pearce WJ, Ingber DE, Zhou J (2008) Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1. Circulation 117:1161–1171PubMedCrossRefGoogle Scholar
  42. 42.
    Boulter C, Mulroy S, Webb S, Fleming S, Brindle K, Sandford R (2001) Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene. Proc Natl Acad Sci U S A 98:12174–12179PubMedCrossRefGoogle Scholar
  43. 43.
    Voets T, Nilius B (2009) TRPCs, GPCRs and the Bayliss effect. EMBO J 28:4–5PubMedCrossRefGoogle Scholar
  44. 44.
    Brayden JE, Earley S, Nelson MT, Reading S (2008) Transient receptor potential (TRP) channels, vascular tone and autoregulation of cerebral blood flow. Clin Exp Pharmacol Physiol 35:1116–1120PubMedCrossRefGoogle Scholar
  45. 45.
    Sharif-Naeini R, Folgering JH, Bichet D, Duprat F, Lauritzen I, Arhatte M, Jodar M, Dedman A, Chatelain FC, Schulte U, Retailleau K, Loufrani L, Patel A, Sachs F, Delmas P, Peters DJ, Honore E (2009) Polycystin-1 and −2 dosage regulates pressure sensing. Cell 139:587–596PubMedCrossRefGoogle Scholar
  46. 46.
    Nilius B (2009) Polycystins under pressure. Cell 139:466–467PubMedCrossRefGoogle Scholar
  47. 47.
    Xiao Z, Zhang S, Mahlios J, Zhou G, Magenheimer BS, Guo D, Dallas SL, Maser R, Calvet JP, Bonewald L, Quarles LD (2006) Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression. J Biol Chem 281:30884–30895PubMedCrossRefGoogle Scholar
  48. 48.
    Xiao Z, Zhang S, Magenheimer BS, Luo J, Quarles LD (2008) Polycystin-1 regulates skeletogenesis through stimulation of the osteoblast-specific transcription factor RUNX2-II. J Biol Chem 283:12624–12634PubMedCrossRefGoogle Scholar
  49. 49.
    Xiao Z, Dallas M, Qiu N, Nicolella D, Cao L, Johnson M, Bonewald L, Quarles LD (2011) Conditional deletion of Pkd1 in osteocytes disrupts skeletal mechanosensing in mice. FASEB J 25:2418–2432PubMedCrossRefGoogle Scholar
  50. 50.
    Lu W, Shen X, Pavlova A, Lakkis M, Ward CJ, Pritchard L, Harris PC, Genest DR, Perez-Atayde AR, Zhou J (2001) Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects. Hum Mol Genet 10:2385–2396PubMedCrossRefGoogle Scholar
  51. 51.
    Watnick TJ, Torres VE, Gandolph MA, Qian F, Onuchic LF, Klinger KW, Landes G, Germino GG (1998) Somatic mutation in individual liver cysts supports a two-hit model of cystogenesis in autosomal dominant polycystic kidney disease. Mol Cell 2:247–251PubMedCrossRefGoogle Scholar
  52. 52.
    Cameron JR (1961) Bilateral “hereditary” polycystic disease of the kidneys associated with bilateral teratodactyly of the feet. Br J Urol 33:473–477PubMedCrossRefGoogle Scholar
  53. 53.
    Pretorius DH, Lee ME, Manco-Johnson ML, Weingast GR, Sedman AB, Gabow PA (1987) Diagnosis of autosomal dominant polycystic kidney disease in utero and in the young infant. J Ultrasound Med 6:249–255PubMedGoogle Scholar
  54. 54.
    Turco AE, Padovani EM, Chiaffoni GP, Peissel B, Rossetti S, Marcolongo A, Gammaro L, Maschio G, Pignatti PF (1993) Molecular genetic diagnosis of autosomal dominant polycystic kidney disease in a newborn with bilateral cystic kidneys detected prenatally and multiple skeletal malformations. J Med Genet 30:419–422PubMedCrossRefGoogle Scholar
  55. 55.
    Ubara Y, Higa Y, Tagami T, Suwabe T, Nomura K, Kadoguchi K, Hoshino J, Sawa N, Katori H, Takemoto F, Kitajima I, Hara S, Takaichi K (2005) Pelvic insufficiency fracture related to autosomal dominant polycystic kidney disease. Am J Kidney Dis 46:e103–e111PubMedCrossRefGoogle Scholar
  56. 56.
    Feather SA, Winyard PJ, Dodd S, Woolf AS (1997) Oral-facial-digital syndrome type 1 is another dominant polycystic kidney disease: clinical, radiological and histopathological features of a new kindred. Nephrol Dial Transplant 12:1354–1361PubMedCrossRefGoogle Scholar
  57. 57.
    Feather SA, Woolf AS, Donnai D, Malcolm S, Winter RM (1997) The oral-facial-digital syndrome type 1 (OFD1), a cause of polycystic kidney disease and associated malformations, maps to Xp22.2–Xp22.3. Hum Mol Genet 6:1163–1167PubMedCrossRefGoogle Scholar
  58. 58.
    Ramos FJ, Kaplan BS, Bellah RD, Zackai EH, Kaplan P (1998) Further evidence that the Hajdu-Cheney syndrome and the “serpentine fibula-polycystic kidney syndrome” are a single entity. Am J Med Genet 78:474–481PubMedCrossRefGoogle Scholar
  59. 59.
    Isidor B, Le Merrer M, Exner GU, Pichon O, Thierry G, Guiochon-Mantel A, David A, Cormier-Daire V, Le Caignec C (2011) Serpentine fibula-polycystic kidney syndrome caused by truncating mutations in NOTCH2. Hum Mutat 32:1239–1242PubMedCrossRefGoogle Scholar
  60. 60.
    Gray MJ, Kim CA, Bertola DR, Arantes PR, Stewart H, Simpson MA, Irving MD, Robertson SP (2012) Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu-Cheney syndrome. Eur J Hum Genet 20:122–124PubMedCrossRefGoogle Scholar
  61. 61.
    Anoop UR, Verma K, Narayanan K (2011) Primary cilia in the pathogenesis of dentigerous cyst: a new hypothesis based on role of primary cilia in autosomal dominant polycystic kidney disease. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 111:608–617PubMedCrossRefGoogle Scholar
  62. 62.
    Liu S, Quarles LD (2007) How fibroblast growth factor 23 works. J Am Soc Nephrol 18:1637–1647PubMedCrossRefGoogle Scholar
  63. 63.
    Yamazaki Y, Tamada T, Kasai N, Urakawa I, Aono Y, Hasegawa H, Fujita T, Kuroki R, Yamashita T, Fukumoto S, Shimada T (2008) Anti-FGF23 neutralizing antibodies show the physiological role and structural features of FGF23. J Bone Miner Res 23:1509–1518PubMedCrossRefGoogle Scholar
  64. 64.
    Yoshiko Y, Wang H, Minamizaki T, Ijuin C, Yamamoto R, Suemune S, Kozai K, Tanne K, Aubin JE, Maeda N (2007) Mineralized tissue cells are a principal source of FGF23. Bone 40:1565–1573PubMedCrossRefGoogle Scholar
  65. 65.
    Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19:429–435PubMedCrossRefGoogle Scholar
  66. 66.
    Razzaque MS (2009) Does FGF23 toxicity influence the outcome of chronic kidney disease? Nephrol Dial Transplant 24:4–7PubMedCrossRefGoogle Scholar
  67. 67.
    Krajisnik T, Bjorklund P, Marsell R, Ljunggren O, Akerstrom G, Jonsson KB, Westin G, Larsson TE (2007) Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol 195:125–131PubMedCrossRefGoogle Scholar
  68. 68.
    Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M, Sirkis R, Naveh-Many T, Silver J (2007) The parathyroid is a target organ for FGF23 in rats. J Clin Invest 117:4003–4008PubMedGoogle Scholar
  69. 69.
    Bacchetta J, Sea JL, Chun RF, Lisse TS, Wesseling-Perry K, Gales B, Adams JS, Salusky IB, Hewison M (2012) FGF23 inhibits extra-renal synthesis of 1,25-dihydroxyvitamin D in human monocytes. J Bone Miner Res 28:46–55CrossRefGoogle Scholar
  70. 70.
    Kurosu H, Kuro OM (2009) The Klotho gene family as a regulator of endocrine fibroblast growth factors. Mol Cell Endocrinol 299:72–78PubMedCrossRefGoogle Scholar
  71. 71.
    Farrow EG, Davis SI, Summers LJ, White KE (2009) Initial FGF23-mediated signaling occurs in the distal convoluted tubule. J Am Soc Nephrol 20:955–960PubMedCrossRefGoogle Scholar
  72. 72.
    Hu MC, Shi M, Zhang J, Pastor J, Nakatani T, Lanske B, Razzaque MS, Rosenblatt KP, Baum MG, Kuro-o M, Moe OW (2010) Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J 24:3438–3450PubMedCrossRefGoogle Scholar
  73. 73.
    Chang Q, Hoefs S, van der Kemp AW, Topala CN, Bindels RJ, Hoenderop JG (2005) The beta-glucuronidase klotho hydrolyzes and activates the TRPV5 channel. Science 310:490–493PubMedCrossRefGoogle Scholar
  74. 74.
    Juppner H, Wolf M, Salusky IB (2010) FGF-23: more than a regulator of renal phosphate handling? J Bone Miner Res 25:2091–2097PubMedCrossRefGoogle Scholar
  75. 75.
    Prie D, Urena Torres P, Friedlander G (2009) Latest findings in phosphate homeostasis. Kidney Int 75:882–889PubMedCrossRefGoogle Scholar
  76. 76.
    Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutierrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M (2011) Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 305:2432–2439PubMedCrossRefGoogle Scholar
  77. 77.
    Mirza MA, Hansen T, Johansson L, Ahlstrom H, Larsson A, Lind L, Larsson TE (2009) Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transplant 24:3125–3131PubMedCrossRefGoogle Scholar
  78. 78.
    Mirza MA, Larsson A, Lind L, Larsson TE (2009) Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 205:385–390PubMedCrossRefGoogle Scholar
  79. 79.
    Fukagawa M, Nii-Kono T, Kazama JJ (2005) Role of fibroblast growth factor 23 in health and in chronic kidney disease. Curr Opin Nephrol Hypertens 14:325–329PubMedCrossRefGoogle Scholar
  80. 80.
    Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592PubMedCrossRefGoogle Scholar
  81. 81.
    Nakanishi S, Kazama JJ, Nii-Kono T, Omori K, Yamashita T, Fukumoto S, Gejyo F, Shigematsu T, Fukagawa M (2005) Serum fibroblast growth factor-23 levels predict the future refractory hyperparathyroidism in dialysis patients. Kidney Int 67:1171–1178PubMedCrossRefGoogle Scholar
  82. 82.
    Srivaths PR, Goldstein SL, Silverstein DM, Krishnamurthy R, Brewer ED (2011) Elevated FGF 23 and phosphorus are associated with coronary calcification in hemodialysis patients. Pediatr Nephrol 26:945–951PubMedCrossRefGoogle Scholar
  83. 83.
    Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, Gutierrez OM, Aguillon-Prada R, Lincoln J, Hare JM, Mundel P, Morales A, Scialla J, Fischer M, Soliman EZ, Chen J, Go AS, Rosas SE, Nessel L, Townsend RR, Feldman HI, St John Sutton M, Ojo A, Gadegbeku C, Di Marco GS, Reuter S, Kentrup D, Tiemann K, Brand M, Hill JA, Moe OW, Kuro OM, Kusek JW, Keane MG, Wolf M (2011) FGF23 induces left ventricular hypertrophy. J Clin Invest 121:4393–4408PubMedCrossRefGoogle Scholar
  84. 84.
    Marsell R, Krajisnik T, Goransson H, Ohlsson C, Ljunggren O, Larsson TE, Jonsson KB (2008) Gene expression analysis of kidneys from transgenic mice expressing fibroblast growth factor-23. Nephrol Dial Transplant 23:827–833PubMedCrossRefGoogle Scholar
  85. 85.
    Bacchetta J, Dubourg L, Harambat J, Ranchin B, Abou-Jaoude P, Arnaud S, Carlier MC, Richard M, Cochat P (2010) The influence of glomerular filtration rate and age on fibroblast growth factor 23 serum levels in pediatric chronic kidney disease. J Clin Endocrinol Metab 95:1741–1748PubMedCrossRefGoogle Scholar
  86. 86.
    Yamazaki Y, Imura A, Urakawa I, Shimada T, Murakami J, Aono Y, Hasegawa H, Yamashita T, Nakatani K, Saito Y, Okamoto N, Kurumatani N, Namba N, Kitaoka T, Ozono K, Sakai T, Hataya H, Ichikawa S, Imel EA, Econs MJ, Nabeshima Y (2010) Establishment of sandwich ELISA for soluble alpha-Klotho measurement: age-dependent change of soluble alpha-Klotho levels in healthy subjects. Biochem Biophys Res Commun 398:513–518PubMedCrossRefGoogle Scholar
  87. 87.
    Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS (2012) Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367:2407–2418PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2013

Authors and Affiliations

  1. 1.Department of Pediatric NephrologyUniversity Hospital of LeuvenLeuvenBelgium
  2. 2.Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular MedicineKU Leuven, Campus Gasthuisberg O&N ILeuvenBelgium
  3. 3.Centre de Référence des Maladies Rénales RaresHôpital Femme Mère Enfant, Hospices Civils de LyonBronFrance
  4. 4.Université de LyonLyonFrance
  5. 5.Institut de Génomique Fonctionnelle de Lyon (IGFL), Ecole Normale SupérieureLyonFrance

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