Renal phosphate handling in human-what can we learn from hereditary hypophosphataemias?

European Journal of Clinical Investigation

Volumn 40, Issue 6, 2010, Pages 552-560

  Amatschek, Stefan ^a   Haller, Maria ^a   Oberbauer, Rainer ^a,b  

^a KH Elisabethinen ^*  (Austria)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

FGF23; Hypophosphataemia; Kidney; Klotho; Renal phosphate reabsorption

Indexed keywords

ANTIPORTER; DENTIN MATRIX PROTEIN 1; FIBROBLAST GROWTH FACTOR 23; KLOTHO PROTEIN; PHOSPHATE; PHOSPHATE REGULATING NEUTRAL ENDOPEPTIDASE; SODIUM HYDROGEN EXCHANGER REGULATORY FACTOR 1; SODIUM PHOSPHATE COTRANSPORTER 2A; SODIUM PHOSPHATE COTRANSPORTER 2C; UNCLASSIFIED DRUG;

FAMILIAL HYPOPHOSPHATEMIC RICKETS; GENE MUTATION; GENETIC ASSOCIATION; HUMAN; KIDNEY TUBULE ABSORPTION; MUTATIONAL ANALYSIS; NONHUMAN; OSTEOCLAST; OSTEOCYTE; PATHOGENESIS; PHOSPHATE BALANCE; PHOSPHATE BLOOD LEVEL; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

EXTRACELLULAR MATRIX PROTEINS; FIBROBLAST GROWTH FACTORS; GLUCURONIDASE; HUMANS; HYPOPHOSPHATEMIA; HYPOPHOSPHATEMIC RICKETS, X-LINKED DOMINANT; KIDNEY; NEPHROLITHIASIS; ORGANIC ANION TRANSPORTERS, SODIUM-DEPENDENT; OSTEOPOROSIS; PHEX PHOSPHATE REGULATING NEUTRAL ENDOPEPTIDASE; PHOSPHATES; PHOSPHOPROTEINS; RICKETS; SODIUM-HYDROGEN ANTIPORTER;

EID: 77952610784     PISSN: 00142972     EISSN: 13652362     Source Type: Journal    
DOI: 10.1111/j.1365-2362.2010.02286.x     Document Type: Review

References (75)

1. Murer H, Forster I, Biber J. The sodium phosphate cotransporter family SLC34. Pflugers Arch 2004 447: 763 767.
2. Forster IC, Hernando N, Biber J, Murer H. Proximal tubular handling of phosphate: a molecular perspective. Kidney Int 2006 70: 1548 1559.
3. Razzaque MS. The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrinol 2009 5: 611 619.
4. Strom TM, Juppner H. PHEX, FGF23, DMP1 and beyond. Curr Opin Nephrol Hypertens 2008 17: 357 362.
5. Berndt T, Thomas LF, Craig TA, Sommer S, Li X, Bergstralh EJ et al. Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption. Proc Natl Acad Sci USA 2007 104: 11085 11090.
6. Wagner CA, Biber J, Murer H. What goes in must come out-the small intestine modulates renal phosphate excretion. Nephrol Dial Transplant 2007 22: 3411 3412.
7. Murer H, Hernando N, Forster I, Biber J. Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol Rev 2000 80: 1373 1409.
8. Werner A, Moore ML, Mantei N, Biber J, Semenza G, Murer H. Cloning and expression of cDNA for a Na/Pi cotransport system of kidney cortex. Proc Natl Acad Sci USA 1991 88: 9608 9612.
9. Custer M, Lotscher M, Biber J, Murer H, Kaissling B. Expression of Na-P(i) cotransport in rat kidney: localization by RT-PCR and immunohistochemistry. Am J Physiol 1994 266: F767 74.
10. Custer M, Meier F, Schlatter E, Greger R, Garcia-Perez A, Biber J et al. Localization of NaPi-1, a Na-Pi cotransporter, in rabbit kidney proximal tubules. I. mRNA localization by reverse transcription/polymerase chain reaction. Pflugers Arch 1993 424: 203 209.
11. Villa-Bellosta R, Ravera S, Sorribas V, Stange G, Levi M, Murer H 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: F691 9.
12. Villa-Bellosta R, Sorribas V. Compensatory regulation of the sodium/phosphate cotransporters NaPi-IIc (SCL34A3) and Pit-2 (SLC20A2) during Pi deprivation and acidosis. Pflugers Arch 2009 459: 499 508.
13. Tenenhouse HS, Roy S, Martel J, Gauthier C. Differential expression, abundance, and regulation of Na+-phosphate cotransporter genes in murine kidney. Am J Physiol 1998 275: F527 34.
14. Jutabha P, Kanai Y, Hosoyamada M, Chairoungdua A, Kim DK, Iribe Y et al. Identification of a novel voltage-driven organic anion transporter present at apical membrane of renal proximal tubule. J Biol Chem 2003 278: 27930 27938.
15. Anzai N, Jutabha P, Kanai Y, Endou H. Integrated physiology of proximal tubular organic anion transport. Curr Opin Nephrol Hypertens 2005 14: 472 479.
16. Verri T, Markovich D, Perego C, Norbis F, Stange G, Sorribas V et al. Cloning of a rabbit renal Na-Pi cotransporter, which is regulated by dietary phosphate. Am J Physiol 1995 268: F626 33.
17. Beck L, Karaplis AC, Amizuka N, Hewson AS, Ozawa H, Tenenhouse HS. Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities. Proc Natl Acad Sci USA 1998 95: 5372 5377.
18. Wagner CA, Biber J, Murer H. Of men and mice: who is in control of renal phosphate reabsorption? J Am Soc Nephrol 2008 19: 1625 1626.
19. Tenenhouse HS, Martel J, Gauthier C, Segawa H, Miyamoto K. Differential effects of Npt2a gene ablation and X-linked Hyp mutation on renal expression of Npt2c. Am J Physiol Renal Physiol 2003 285: F1271 8.
20. Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I et al. Growth-related renal type II Na/Pi cotransporter. J Biol Chem 2002 277: 19665 19672.
21. Segawa H, Yamanaka S, Ito M, Kuwahata M, Shono M, Yamamoto T et al. Internalization of renal type IIc Na-Pi cotransporter in response to a high-phosphate diet. Am J Physiol Renal Physiol 2005 288: F587 96.
22. Segawa H, Yamanaka S, Onitsuka A, Tomoe Y, Kuwahata M, Ito M et al. Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter. Am J Physiol Renal Physiol 2007 292: F395 403.
23. Prie D, Huart V, Bakouh N, Planelles G, Dellis O, Gerard B et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 2002 347: 983 991.
24. Virkki LV, Forster IC, Hernando N, Biber J, Murer H. Functional characterization of two naturally occurring mutations in the human sodium-phosphate cotransporter type IIa. J Bone Miner Res 2003 18: 2135 2141.
25. Lapointe JY, Tessier J, Paquette Y, Wallendorff B, Coady MJ, Pichette V et al. NPT2a gene variation in calcium nephrolithiasis with renal phosphate leak. Kidney Int 2006 69: 2261 2267.
26. Tieder M, Modai D, Samuel R, Arie R, Halabe A, Bab I et al. Hereditary hypophosphatemic rickets with hypercalciuria. N Engl J Med 1985 312: 611 617.
27. Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H et al. SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet 2006 78: 179 192.
28. Lorenz-Depiereux B, Benet-Pages A, Eckstein G, Tenenbaum-Rakover Y, Wagenstaller J, Tiosano D et al. Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am J Hum Genet 2006 78: 193 201.
29. Ichikawa S, Sorenson AH, Imel EA, Friedman NE, Gertner JM, Econs MJ. Intronic deletions in the SLC34A3 gene cause hereditary hypophosphatemic rickets with hypercalciuria. J Clin Endocrinol Metab 2006 91: 4022 4027.
30. Jaureguiberry G, Carpenter TO, Forman S, Juppner H, Bergwitz C. A novel missense mutation in SLC34A3 that causes hereditary hypophosphatemic rickets with hypercalciuria in humans identifies threonine 137 as an important determinant of sodium-phosphate cotransport in NaPi-IIc. Am J Physiol Renal Physiol 2008 295: F371 9.
31. Tencza AL, Ichikawa S, Dang A, Kenagy D, McCarthy E, Econs MJ et al. Hypophosphatemic rickets with hypercalciuria due to mutation in SLC34A3/type IIc sodium-phosphate cotransporter: presentation as hypercalciuria and nephrolithiasis. J Clin Endocrinol Metab 2009 94: 4433 4438.
32. Ohkido I, Segawa H, Yanagida R, Nakamura M, Miyamoto K. Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney. Pflugers Arch 2003 446: 106 115.
33. Segawa H, Onitsuka A, Furutani J, Kaneko I, Aranami F, Matsumoto N et al. Npt2a and Npt2c in mice play distinct and synergistic roles in inorganic phosphate metabolism and skeletal development. Am J Physiol Renal Physiol 2009 297: F671 8.
34. Keusch I, Traebert M, Lotscher M, Kaissling B, Murer H, Biber J. Parathyroid hormone and dietary phosphate provoke a lysosomal routing of the proximal tubular Na/Pi-cotransporter type II. Kidney Int 1998 54: 1224 1232.
35. Pfister MF, Lederer E, Forgo J, Ziegler U, Lotscher M, Quabius ES et al. Parathyroid hormone-dependent degradation of type II Na+/Pi cotransporters. J Biol Chem 1997 272: 20125 20130.
36. Kumar R. Tumor-induced osteomalacia and the regulation of phosphate homeostasis. Bone 2000 27: 333 338.
37. ADHR-Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 2000 26: 345 348.
38. 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: 3179 3182.
39. Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S et al. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 2001 98: 6500 6505.
40. Shimada T, Urakawa I, Yamazaki Y, Hasegawa H, Hino R, Yoneya T et al. FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa. Biochem Biophys Res Commun 2004 314: 409 414.
41. Segawa H, Kawakami E, Kaneko I, Kuwahata M, Ito M, Kusano K et al. Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter. Pflugers Arch 2003 446: 585 592.
42. Gattineni J, Bates C, Twombley K, Dwarakanath V, Robinson ML, Goetz R et al. FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. Am J Physiol Renal Physiol 2009 297: F282 91.
43. Baum M, Schiavi S, Dwarakanath V, Quigley R. Effect of fibroblast growth factor-23 on phosphate transport in proximal tubules. Kidney Int 2005 68: 1148 1153.
44. Yamashita T, Konishi M, Miyake A, Inui K, Itoh N. Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway. J Biol Chem 2002 277: 28265 28270.
45. Bacic D, Schulz N, Biber J, Kaissling B, Murer H, Wagner CA. Involvement of the MAPK-kinase pathway in the PTH-mediated regulation of the proximal tubule type IIa Na+/Pi cotransporter in mouse kidney. Pflugers Arch 2003 446: 52 60.
46. Kawata T, Imanishi Y, Kobayashi K, Miki T, Arnold A, Inaba M et al. Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. J Am Soc Nephrol 2007 18: 2683 2688.
47. Saito H, Maeda A, Ohtomo S, Hirata M, Kusano K, Kato S et al. Circulating FGF-23 is regulated by 1alpha,25-dihydroxyvitamin D3 and phosphorus in vivo. J Biol Chem 2005 280: 2543 2549.
48. 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: 4003 4008.
49. 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: 429 435.
50. Mirams M, Robinson BG, Mason RS, Nelson AE. Bone as a source of FGF23: regulation by phosphate? Bone 2004 35: 1192 1199.
51. 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: E38 49.
52. 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: 770 774.
53. Xiao L, Naganawa T, Lorenzo J, Carpenter TO, Coffin JD, Hurley MM. Nuclear isoforms of fibroblast growth factor 2 are novel inducers of hypophosphatemia via modulation of FGF23 and klotho. J Biol Chem 2009 285: 2834 2846.
54. 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: 45 51.
55. Farrow EG, Davis SI, Summers LJ, White KE. Initial FGF23-mediated signaling occurs in the distal convoluted tubule. J Am Soc Nephrol 2009 20: 955 960.
56. Brownstein CA, Adler F, Nelson-Williams C, Iijima J, Li P, Imura A et al. A translocation causing increased alpha-klotho level results in hypophosphatemic rickets and hyperparathyroidism. Proc Natl Acad Sci USA 2008 105: 3455 3460.
57. Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH et al. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Musculoskelet Neuronal Interact 2007 7: 318 319.
58. Francis F, Hennig S, Korn B, Reinhardt R, de Jong P, Poustka A et al. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. The HYP Consortium. Nat Genet 1995 11: 130 136.
59. Beck L, Soumounou Y, Martel J, Krishnamurthy G, Gauthier C, Goodyer CG et al. Pex/PEX tissue distribution and evidence for a deletion in the 3′ region of the Pex gene in X-linked hypophosphatemic mice. J Clin Invest 1997 99: 1200 1209.
60. Tenenhouse HS. X-linked hypophosphataemia: a homologous disorder in humans and mice. Nephrol Dial Transplant 1999 14: 333 341.
61. Sabbagh Y, Jones AO, Tenenhouse HS. PHEXdb, a locus-specific database for mutations causing X-linked hypophosphatemia. Hum Mutat 2000 16: 1 6.
62. Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R et al. FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. Biochem Biophys Res Commun 2001 284: 977 981.
63. Campos M, Couture C, Hirata IY, Juliano MA, Loisel TP, Crine P et al. Human recombinant endopeptidase PHEX has a strict S1' specificity for acidic residues and cleaves peptides derived from fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein. Biochem J 2003 373: 271 279.
64. 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: 37419 37426.
65. Benet-Pages A, Lorenz-Depiereux B, Zischka H, White KE, Econs MJ, Strom TM. FGF23 is processed by proprotein convertases but not by PHEX. Bone 2004 35: 455 462.
66. 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: 421 432.
67. Yuan B, Takaiwa M, Clemens TL, Feng JQ, Kumar R, Rowe PS et al. Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X-linked hypophosphatemia. J Clin Invest 2008 118: 722 734.
68. 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: 1310 1315.
69. Liu S, Zhou J, Tang W, Menard R, Feng JQ, Quarles LD. Pathogenic role of Fgf23 in Dmp1-null mice. Am J Physiol Endocrinol Metab 2008 295: E254 61.
70. Karim Z, Gerard B, Bakouh N, Alili R, Leroy C, Beck L et al. NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med 2008 359: 1128 1135.
71. Hernando N, Deliot N, Gisler SM, Lederer E, Weinman EJ, Biber J et al. PDZ-domain interactions and apical expression of type IIa Na/P(i) cotransporters. Proc Natl Acad Sci USA 2002 99: 11957 11962.
72. Shenolikar S, Voltz JW, Minkoff CM, Wade JB, Weinman EJ. Targeted disruption of the mouse NHERF-1 gene promotes internalization of proximal tubule sodium-phosphate cotransporter type IIa and renal phosphate wasting. Proc Natl Acad Sci USA 2002 99: 11470 11475.
73. Villa-Bellosta R, Barac-Nieto M, Breusegem SY, Barry NP, Levi M, Sorribas V. Interactions of the growth-related, type IIc renal sodium/phosphate cotransporter with PDZ proteins. Kidney Int 2008 73: 456 464.
74. Markovich D, Verri T, Sorribas V, Forgo J, Biber J, Murer H. Regulation of opossum kidney (OK) cell Na/Pi cotransport by Pi deprivation involves mRNA stability. Pflugers Arch 1995 430: 459 463.
75. Martin DR, Ritter CS, Slatopolsky E, Brown AJ. Acute regulation of parathyroid hormone by dietary phosphate. Am J Physiol Endocrinol Metab 2005 289: E729 34.