Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism

Nature Reviews Nephrology

Volumn 9, Issue 11, 2013, Pages 650-660

  Kuro O, Makoto ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; CALCIPROTEIN; CALCIUM; CALCIUM PHOSPHATE; FETUIN A; FIBROBLAST GROWTH FACTOR; FIBROBLAST GROWTH FACTOR 15; FIBROBLAST GROWTH FACTOR 19; FIBROBLAST GROWTH FACTOR 23; GROWTH HORMONE; KLOTHO PROTEIN; LIGAND; NANOPARTICLE; PHOSPHATE; PROTEIN DERIVATIVE; SOMATOMEDIN C; UNCLASSIFIED DRUG;

BLOOD VESSEL CALCIFICATION; CELL DEATH; CELL TRANSFORMATION; CHRONIC KIDNEY DISEASE; CYTOTOXICITY; FIBROSING ALVEOLITIS; HOMEOSTASIS; HUMAN; HYPERPHOSPHATEMIA; KIDNEY TUBULE DAMAGE; KIDNEY TUBULE EPITHELIUM; MINERAL METABOLISM; NONHUMAN; PATHOGENESIS; PATHOPHYSIOLOGY; PHENOTYPE; PHOSPHATE BLOOD LEVEL; PREMATURE AGING; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; URINARY EXCRETION; VASCULAR ENDOTHELIUM; VASCULAR SMOOTH MUSCLE;

AGING; ANIMALS; FIBROBLAST GROWTH FACTORS; GLUCURONIDASE; HUMANS; HYPERPHOSPHATEMIA; MINERALS; PHOSPHATES; RENAL INSUFFICIENCY, CHRONIC;

EID: 84890807103     PISSN: 17595061     EISSN: 1759507X     Source Type: Journal    
DOI: 10.1038/nrneph.2013.111     Document Type: Review

References (125)

1. Wolfe-Simon, F. et al. A bacterium that can grow by using arsenic instead of phosphorus. Science 332, 1163-1166 (2011).
2. Hiza, H., Bente, L. & Fungwe, T. Nutrient content of the US food supply, 2005. US Department of Agriculture, Center for Nutritional Policy and Promotion [online], http://www.cnpp.usda.gov/Publications/Foodsupply/ Foodsupply2005Report.pdf (2008).
3. Uribarri, J. Phosphorus additives in food and their effect in dialysis patients. Clin. J. Am. Soc. Nephrol. 4, 1290-1292 (2009).
4. Schiavi, S. C. & Kumar, R. The phosphatonin pathway: New insights in phosphate homeostasis. Kidney Int. 65, 1-14 (2004).
5. Mitchell, H. H., Hamilton, T. S., Steggerda, F. R. & Bean, H. W. The chemical composition of the adult human body and its bearing on the biochemistry of growth. J. Biol. Chem. 96, 625-637 (1945).
6. Kuroo, M. Phosphate and Klotho. Kidney Int. Suppl. 79, S20-S23 (2011).
7. Shimada, T. et al. FGF 23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J. Bone Miner. Res. 19, 429-435 (2004).
8. White, K. E. et al. Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF 23. Kidney Int. 60, 2079-2086 (2001).
9. Ben-Dov, I. Z. et al. The parathyroid is a target organ for FGF23 in rats. J. Clin. Invest. 117, 4003-4008 (2007).
10. Kurosu, H. et al. Regulation of fibroblast growth factor 23 signaling by klotho. J. Biol. Chem. 281, 6120-6123 (2006).
11. Urakawa, I. et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 444, 770-774 (2006).
12. Kuroo, M. et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390, 45-51 (1997).
13. Azuma, M. et al. Promoter methylation confers kidney-specific expression of the Klotho gene. FASEB J. 26, 4264-4274 (2012).
14. Nagai, T. et al. Cognition impairment in the genetic model of aging klotho gene mutant mice: A role of oxidative stress. FASEB J. 17, 50-52 (2003).
15. Kamemori, M. et al. Expression of Klotho protein in the inner ear. Hear. Res. 171, 103-110 (2002).
16. Toyama, R. et al. Impaired regulation of gonadotropins leads to the atrophy of the female reproductive system in klotho-deficient mice. Endocrinology 147, 120-129 (2006).
17. Faul, C. et al. FGF23 induces left ventricular hypertrophy. J. Clin. Invest. 121, 4393-4408 (2011).
18. Suga, T. et al. Disruption of the klotho gene causes pulmonary emphysema in mice. Defect in maintenance of pulmonary integrity during postnatal life. Am. J. Respir. Cell Mol. Biol. 22, 26-33 (2000).
19. Kawaguchi, H. et al. Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia. J. Clin. Invest. 104, 229-237 (1999).
20. 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. 17, 2393-2403 (2003).
21. Shimada, T. et al. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J. Clin. Invest. 113, 561-568 (2004).
22. Farrow, E. G., Davis, S. I., Summers, L. J. & White, K. E. Initial FGF23-mediated signaling occurs in the distal convoluted tubule. J. Am. Soc. Nephrol. 20, 955-960 (2009).
23. Olauson, H. et al. Targeted deletion of Klotho in kidney distal tubule disrupts mineral metabolism. J. Am. Soc. Nephrol. 23, 1641-1651 (2012).
24. Goetz, R. et al. Molecular insights into the Klotho-dependent, endocrine mode of action of FGF19 subfamily members. Mol. Cell Biol. 27, 3417-3428 (2007).
25. Inagaki, T. et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2, 217-225 (2005).
26. Choi, M. et al. Identification of a hormonal basis for gallbladder filling. Nat. Med. 12, 1253-1255 (2006).
27. Kir, S. et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science 331, 1621-1624 (2011).
28. Kharitonenkov, A. et al. FGF 21 as a novel metabolic regulator. J. Clin. Invest. 115, 1627-1635 (2005).
29. Inagaki, T. et al. Endocrine regulation of the fasting response by PPARα-mediated induction of fibroblast growth factor 21. Cell Metab. 5, 415-425 (2007).
30. Potthoff, M. J. et al. FGF21 induces PGC-1α and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. Proc. Natl Acad. Sci. USA 106, 10853-10858 (2009).
31. Badman, M. K. et al. Hepatic fibroblast growth factor 21 is regulated by PPARα and is a key mediator of hepatic lipid metabolism in ketotic states. Cell. Metab. 5, 426-437 (2007).
32. Potthoff, M. J., Kliewer, S. A. & Mangelsdorf, D. J. Endocrine fibroblast growth factors 15/19 and 21: From feast to famine. Genes Dev. 26, 312-324 (2012).
33. Ito, S. et al. Molecular cloning and expression analyses of mouse betaklotho, which encodes a novel Klotho family protein. Mech. Dev. 98, 115-119 (2000).
34. Ogawa, Y. et al. βKlotho is required for metabolic activity of fibroblast growth factor 21. Proc. Natl Acad. Sci. USA 104, 7432-7437 (2007).
35. Kurosu, H. et al. Tissue-specific expression of βKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J. Biol. Chem. 282, 26687-26695 (2007).
36. Masuyama, R. et al. Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts. J. Clin. Invest. 116, 3150-3159 (2006).
37. Kuroo, M. Endocrine FGFs and Klothos: Emerging concepts. Trends Endocrinol. Metab. 19, 239-245 (2008).
38. Kuroo, M. (Ed.) Endocrine FGFs and Klothos (Landes Bioscience and Springer Science, New York, 2012).
39. Stubbs, J. R. 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. 18, 2116-2124 (2007).
40. Hesse, M., Frohlich, L. F., Zeitz, U., Lanske, B. & Erben, R. G. Ablation of vitamin D signaling rescues bone, mineral, and glucose homeostasis in Fgf 23 deficient mice. Matrix Biol. 26, 75-84 (2007).
41. Razzaque, M. S., Sitara, D., Taguchi, T., St-Arnaud, R. & Lanske, B. Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D mediated process. FASEB J. 20, 720-722 (2006).
42. Ohnishi, M., Nakatani, T., Lanske, B. & Razzaque, M. S. Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1α-hydroxylase. Kidney Int. 75, 1166-1172 (2009).
43. Ohnishi, M. & Razzaque, M. S. Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging. FASEB J. 24, 3562-3571 (2010).
44. Beck, L. et al. Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities. Proc. Natl Acad. Sci. USA 95, 5372-5377 (1998).
45. Ohnishi, M., Nakatani, T., Lanske, B. & Razzaque, M. S. In vivo genetic evidence for suppressing vascular and soft-tissue calcification through the reduction of serum phosphate levels, even in the presence of high serum calcium and 1,25-dihydroxyvitamin-D levels. Circ. Cardiovasc. Genet. 2, 583-590 (2009).
46. Hruska, K. A., Mathew, S., Lund, R., Qiu, P. & Pratt, R. Hyperphosphatemia of chronic kidney disease. Kidney Int. 74, 148-157 (2008).
47. Stenvinkel, P. & Larsson, T. E. Chronic kidney disease: A clinical model of premature aging. Am. J. Kidney Dis. http://dx.doi.org/10.1053/j.ajkd. 2012.11.051.
48. Isakova, T. et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 79, 1370-1378 (2011).
49. Koh, N. et al. Severely reduced production of klotho in human chronic renal failure kidney. Biochem. Biophys. Res. Commun. 280, 1015-1020 (2001).
50. Galitzer, H., Ben-Dov, I. Z., Silver, J. & Naveh-Many, T. Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease. Kidney Int. 77, 211-218 (2010).
51. Komaba, H. et al. Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. Kidney Int. 77, 232-238 (2010).
52. Krajisnik, T. et al. Parathyroid Klotho and FGF-receptor 1 expression decline with renal function in hyperparathyroid patients with chronic kidney disease and kidney transplant recipients. Kidney Int. 78, 1024-1032 (2010).
53. Kumata, C. et al. Involvement of α-klotho and fibroblast growth factor receptor in the development of secondary hyperparathyroidism. Am. J. Nephrol. 31, 230-238 (2010).
54. Kestenbaum, B. et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J. Am. Soc. Nephrol. 16, 520-528 (2005).
55. Ganesh, S. K., Stack, A. G., Levin, N. W., Hulbert-Shearon, T. & Port, F. K. Association of elevated serum PO4, Ca × PO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J. Am. Soc. Nephrol. 12, 2131-2138 (2001).
56. Martin, K. J. & Gonzalez, E. A. Prevention and control of phosphate retention/hyperphosphatemia in CKD-MBD: What is normal, when to start, and how to treat? Clin. J. Am. Soc. Nephrol. 6, 440-446 (2011).
57. Martin, G. M. Genetic syndromes in man with potential relevance to the pathobiology of aging. Birth Defects 14, 5-39 (1978).
58. Lombard, D. B. et al. DNA repair, genome stability, and aging. Cell 120, 497-512 (2005).
59. Rudolph, K. L. et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96, 701-712 (1999).
60. Herbig, U., Jobling, W. A., Chen, B. P., Chen, D. J. & Sedivy, J. M. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21CIP1, but not p16INK4a. Mol. Cell 14, 501-513 (2004).
61. Chin, L. et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527-538 (1999).
62. Choudhury, A. R. et al. Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat. Genet. 39, 99-105 (2007).
63. Tyner, S. D. et al. p53 mutant mice that display early ageing-associated phenotypes. Nature 415, 45-53 (2002).
64. Niedernhofer, L. J. et al. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444, 1038-1043 (2006).
65. Flurkey, K., Papaconstantinou, J., Miller, R. A. & Harrison, D. E. Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc. Natl Acad. Sci. USA 98, 6736-6741 (2001).
66. Ramirez, R. et al. Stress-induced premature senescence in mononuclear cells from patients on long-term hemodialysis. Am. J. Kidney Dis. 45, 353-359 (2005).
67. Smogorzewski, M. J. & Massry, S. G. Liver metabolism in CRF. Am. J. Kidney Dis. 41 (Suppl. 1), S127-S132 (2003).
68. Inagaki, T. et al. Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. Cell Metab. 8, 77-83 (2008).
69. Lin, Z. et al. Circulating FGF21 levels are progressively increased from the early to end stages of chronic kidney diseases and are associated with renal function in Chinese. PLoS ONE 6, e18398 (2011).
70. Han, S. H. et al. Serum fibroblast growth factor 21 concentration is associated with residual renal function and insulin resistance in end-stage renal disease patients receiving long-term peritoneal dialysis. Metabolism 59, 1656-1662 (2010).
71. Zhang, Y. et al. The starvation hormone, fibroblast growth factor 21, extends lifespan in mice. eLife 1, e00065 (2012).
72. Di Marco, G. S. et al. Increased inorganic phosphate induces human endothelial cell apoptosis in vitro. Am. J. Physiol. Renal Physiol. 294, F1381-F1387 (2008).
73. Shuto, E. et al. Dietary phosphorus acutely impairs endothelial function. J. Am. Soc. Nephrol. 20, 1504-1512 (2009).
74. Steitz, S. A. et al. Smooth muscle cell phenotypic transition associated with calcification: Upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ. Res. 89, 1147-1154 (2001).
75. Jono, S. et al. Phosphate regulation of vascular smooth muscle cell calcification. Circ. Res. 87, E10-E17 (2000).
76. Reynolds, J. L. et al. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: A potential mechanism for accelerated vascular calcification in ESRD. J. Am. Soc. Nephrol. 15, 2857-2867 (2004).
77. Sage, A. P., Lu, J., Tintut, Y. & Demer, L. L. Hyperphosphatemia- induced nanocrystals upregulate the expression of bone morphogenetic protein 2 and osteopontin genes in mouse smooth muscle cells in vitro. Kidney Int. 79, 414-422 (2011).
78. Villa-Bellosta, R. & Sorribas, V. Phosphonoformic acid prevents vascular smooth muscle cell calcification by inhibiting calcium-phosphate deposition. Arterioscler. Thromb. Vasc. Biol. 29, 761-766 (2009).
79. Ewence, A. E. et al. Calcium phosphate crystals induce cell death in human vascular smooth muscle cells: A potential mechanism in atherosclerotic plaque destabilization. Circ. Res. 103, e28-e34 (2008).
80. Li, X., Yang, H. Y. & Giachelli, C. M. Role of the sodium-dependent phosphate cotransporter, Pit 1, in vascular smooth muscle cell calcification. Circ. Res. 98, 905-912 (2006).
81. Nancollas, G. H., LoRe, M., Perez, L., Richardson, C. & Zawacki, S. J. Mineral phases of calcium phosphate. Anat. Rec. 224, 234-241 (1989).
82. Pak, C. Y.C., Eanes, E. D. & Ruskin, B. Spontaneous precipitation of brushite in urine: Evidence that brushite Is the nidus of renal stones originating as calcium phosphate. Proc. Natl Acad. Sci. USA 68, 1456-1460 (1971).
83. Heiss, A., Pipich, V., Jahnen-Dechent, W. & Schwahn, D. Fetuin A is a mineral carrier protein: Small angle neutron scattering provides new insight on fetuin a controlled calcification inhibition. Biophys. J. 99, 3986-3995 (2010).
84. Rochette, C. N. et al. A shielding topology stabilizes the early stage protein-mineral complexes of fetuin A and calcium phosphate: A time-resolved small-angle X ray study. Chembiochem. 10, 735-740 (2009).
85. Heiss, A., Jahnen-Dechent, W., Endo, H. & Schwahn, D. Structural dynamics of a colloidal protein-mineral complex bestowing on calcium phosphate a high solubility in biological fluids. Biointerphases 2, 16-20 (2007).
86. Heiss, A. et al. Structural basis of calcification inhibition by α2 HS glycoprotein/fetuin A. Formation of colloidal calciprotein particles. J. Biol. Chem. 278, 13333-13341 (2003).
87. Schafer, C. et al. The serum protein α2 Heremans Schmid glycoprotein/fetuin A is a systemically acting inhibitor of ectopic calcification. J. Clin. Invest. 112, 357-366 (2003).
88. Khoshniat, S. et al. Phosphate-dependent stimulation of MGP and OPN expression in osteoblasts via the ERK1/2 pathway is modulated by calcium. Bone 48, 894-902 (2010).
89. Herrmann, M. et al. Clearance of fetuin A -containing calciprotein particles is mediated by scavenger receptor A. Circ. Res. 111, 575-84 (2012).
90. Hamano, T. et al. Fetuin-mineral complex reflects extraosseous calcification stress in CKD. J. Am. Soc. Nephrol. 21, 1998-2007 (2010).
91. Matsui, I. et al. Fully phosphorylated fetuin A forms a mineral complex in the serum of rats with adenine-induced renal failure. Kidney Int. 75, 915-928 (2009).
92. Smith, E. R. et al. Phosphorylated fetuin A containing calciprotein particles are associated with aortic stiffness and a procalcific milieu in patients with pre-dialysis CKD. Nephrol. Dial. Transplant. 27, 1957-1966 (2012).
93. Block, G. A. et al. Effects of phosphate binders in moderate CKD. J. Am. Soc. Nephrol. 23, 1407-1415 (2012).
94. Rodriguez-Ortiz, M. E. et al. Calcium deficiency reduces circulating levels of FGF23. J. Am. Soc. Nephrol. 23, 1190-1197 (2012).
95. Mackay, E. M. & Oliver, J. Renal damage following the ingestion of a diet containing an excess of inorganic phosphate. J. Exp. Med. 61, 319-334 (1935).
96. Ori, Y. et al. Acute phosphate nephropathy-an emerging threat. Am. J. Med. Sci. 336, 309-314 (2008).
97. Haut, L. L., Alfrey, A. C., Guggenheim, S., Buddington, B. & Schrier, N. Renal toxicity of phosphate in rats. Kidney Int. 17, 722-731 (1980).
98. Bank, N., Su, W. S. & Aynedjian, H. S. A micropuncture study of renal phosphate transport in rats with chronic renal failure and secondary hyperparathyroidism. J. Clin. Invest. 61, 884-894 (1978).
99. Lau, K. Phosphate excess and progressive renal failure: The precipitation-calcification hypothesis. Kidney Int. 36, 918-937 (1989).
100. Aihara, K., Byer, K. J. & Khan, S. R. Calcium phosphate-induced renal epithelial injury and stone formation: Involvement of reactive oxygen species. Kidney Int. 64, 1283-1291 (2003).
101. Miller, P. D. The kidney and bisphosphonates. Bone 49, 77-81 (2011).
102. Francis, M. D., Russell, R. G. & Fleisch, H. Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathological calcification in vivo. Science 165, 1264-1266 (1969).
103. Bertram, J. F., Douglas-Denton, R. N., Diouf, B., Hughson, M. D. & Hoy, W. E. Human nephron number: Implications for health and disease. Pediatr. Nephrol. 26, 1529-1533 (2011).
104. Zhou, X. J. et al. The aging kidney. Kidney Int. 74, 710-720 (2008).
105. Ibrahim, H. N. et al. Long-term consequences of kidney donation. N. Engl. J. Med. 360, 459-469 (2009).
106. Tan, J. C. et al. Effects of aging on glomerular function and number in living kidney donors. Kidney Int. 78, 686-692 (2010).
107. Young, A. et al. Bone and mineral metabolism and fibroblast growth factor 23 levels after kidney donation. Am. J. Kidney Dis. 59, 761-769 (2011).
108. Robertson, W. G. & Morgan, D. B. The distribution of urinary calcium excretions in normal persons and stone-formers. Clin. Chim. Acta 37, 503-508 (1972).
109. Gallagher, J. C. et al. Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients: Effect of age and dietary calcium. J. Clin. Invest. 64, 729-736 (1979).
110. Cebotaru, V. et al. High citrate diet delays progression of renal insufficiency in the ClC 5 knockout mouse model of Dent's disease. Kidney Int. 68, 642-652 (2005).
111. Gutierrez, O. et al. Fibroblast growth factor 23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J. Am. Soc. Nephrol. 16, 2205-2215 (2005).
112. Hasegawa, H. 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. 78, 975-980 (2010).
113. Vervloet, M. G. et al. Effects of dietary phosphate and calcium intake on fibroblast growth factor 23. Clin. J. Am. Soc. Nephrol. 6, 383-389 (2010).
114. Antoniucci, D. M., Yamashita, T. & Portale, A. A. Dietary phosphorus regulates serum fibroblast growth factor 23 concentrations in healthy men. J. Clin. Endocrinol. Metab. 91, 3144-3149 (2006).
115. Ito, N. et al. Effect of acute changes of serum phosphate on fibroblast growth factor (FGF)23 levels in humans. J. Bone Miner. Metab. 25, 419-422 (2007).
116. Gutierrez, O. M., Wolf, M. & Taylor, E. N. Fibroblast growth factor 23, cardiovascular disease risk factors, and phosphorus intake in the health professionals follow-up study. Clin. J. Am. Soc. Nephrol. 6, 2871-2878 (2011).
117. Larsson, T., Nisbeth, U., Ljunggren, O., Juppner, H. & Jonsson, K. B. 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. 64, 2272-2279 (2003).
118. Coresh, J. et al. Prevalence of chronic kidney disease in the United States. JAMA 298, 2038-2047 (2007).
119. Levin, A. 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. 71, 31-38 (2007).
120. Nelson, R. G. & Tuttle, K. R. The new KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and CKD. Blood Purif. 25, 112-114 (2007).
121. Togao, O. et al. Assessment of renal fibrosis with diffusion-weighted MR imaging: Study with murine model of unilateral ureteral obstruction. Radiology 255, 772-780 (2010).
122. Doi, S. et al. Klotho inhibits transforming growth factor β1 (TGF β1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J. Biol. Chem. 286, 8655-8665 (2011).
123. Gutierrez, O. M. & Wolf, M. Dietary phosphorus restriction in advanced chronic kidney disease: Merits, challenges, and emerging strategies. Semin. Dial. 23, 401-406 (2010).
124. Moe, S. M. et al. Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. Clin. J. Am. Soc. Nephrol. 6, 257-264 (2011).
125. Bell, R. R., Draper, H. H., Tzeng, D. Y., Shin, H. K. & Schmidt, G. R. Physiological responses of human adults to foods containing phosphate additives. J. Nutr. 107, 42-50 (1977).