title: Phosphate Metabolism in Cardiorenal Metabolic Disease.
abstract: Hyperphosphatemia is a major risk factor for cardiovascular disease, abnormalities of mineral metabolism and bone disease, and the progression of renal insufficiency in patients with chronic renal disease. In early renal disease, serum phosphate levels are maintained within the 'normal laboratory range' by compensatory increases in phosphaturic hormones such as fibroblast growth factor-23 (FGF-23). An important co-factor for FGF-23 is Klotho; a deficiency in Klotho plays an important role in the pathogenesis of hyperphosphatemia, renal tubulointerstitial disease, and parathyroid and bone abnormalities. Clinical hyperphosphatemia occurs when these phosphaturic mechanisms cannot counterbalance nephron loss. Hyperphosphatemia is associated with calcific uremic arteriolopathy and uremic cardiomyopathy, which may explain, in part, the epidemiologic connections between phosphate excess and cardiovascular disease. However, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy. In summary, hyperphosphatemia accelerates renal tubulointerstitial disease, renal osteodystrophy, as well as cardiovascular disease, and it is an important mortality risk factor in patients with chronic kidney disease.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA.
authors.forename: Deepashree
authors.initials: D
authors.lastname: Gupta
authors.forename: Stephen
authors.initials: S
authors.lastname: Brietzke
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
authors.forename: L Romayne
authors.initials: LR
authors.lastname: Kurukulasuriya
authors.forename: James R
authors.initials: JR
authors.lastname: Sowers
references.citation: Am J Physiol Endocrinol Metab. 2005 Oct;289(4):E729-34
references.pmid: 15914507
references.citation: Kidney Int. 2007 Aug;72(3):247-59
references.pmid: 17568785
references.citation: Cardiorenal Med. 2011;1(1):5-12
references.pmid: 22258461
references.citation: Ther Adv Cardiovasc Dis. 2007 Dec;1(2):107-12
references.pmid: 19124399
references.citation: JAMA. 2007 Nov 7;298(17):2038-47
references.pmid: 17986697
references.citation: Osteoporos Int. 2006 Oct;17(10):1506-13
references.pmid: 16896512
references.citation: Kidney Int. 2010 Feb;77(3):211-8
references.pmid: 20016468
references.citation: J Clin Endocrinol Metab. 2010 Feb;95(2):578-85
references.pmid: 19965919
references.citation: Circ Res. 2000 Sep 29;87(7):E10-7
references.pmid: 11009570
references.citation: Am J Nephrol. 2010;31(3):230-8
references.pmid: 20068287
references.citation: FASEB J. 2010 Sep;24(9):3562-71
references.pmid: 20418498
references.citation: Nephrol Dial Transplant. 2008 Mar;23(3):827-33
references.pmid: 17911089
references.citation: J Am Soc Nephrol. 2004 Aug;15(8):2208-18
references.pmid: 15284307
references.citation: Am J Kidney Dis. 2005 May;45(5):851-8
references.pmid: 15861350
references.citation: Adv Chronic Kidney Dis. 2011 Mar;18(2):113-9
references.pmid: 21406296
references.citation: Nephrol Dial Transplant. 2005 Dec;20(12):2636-45
references.pmid: 16204278
references.citation: Matrix Biol. 2007 Mar;26(2):75-84
references.pmid: 17123805
references.citation: J Am Soc Nephrol. 2007 Jul;18(7):2116-24
references.pmid: 17554146
references.citation: Kidney Int. 2011 Sep;80(5):475-82
references.pmid: 21525854
references.citation: N Engl J Med. 2004 Sep 23;351(13):1296-305
references.pmid: 15385656
references.citation: J Clin Invest. 2007 Dec;117(12):4003-8
references.pmid: 17992255
references.citation: Aging Cell. 2009 Jun;8(3):270-6
references.pmid: 19627266
references.citation: JAMA. 2002 Apr 24;287(16):2081-9
references.pmid: 11966382
references.citation: J Clin Invest. 1997 Aug 1;100(3):538-49
references.pmid: 9239400
references.citation: J Am Soc Nephrol. 2005 Jul;16(7):2205-15
references.pmid: 15917335
references.citation: J Cell Biochem. 2003 Oct 1;90(2):234-43
references.pmid: 14505340
references.citation: Physiology (Bethesda). 2009 Feb;24:17-25
references.pmid: 19196648
references.citation: Kidney Int. 2011 Sep;80(5):443-5
references.pmid: 21841832
references.citation: J Am Soc Nephrol. 2005 Apr;16(4):917-28
references.pmid: 15743994
references.citation: Kidney Int. 2009 Apr;75(8):800-8
references.pmid: 19165175
references.citation: J Clin Invest. 1968 Aug;47(8):1865-74
references.pmid: 5666116
references.citation: Oxid Med Cell Longev. 2010 Mar-Apr;3(2):109-21
references.pmid: 20716935
references.citation: Kidney Int. 2009 Jun;75(11):1166-1172
references.pmid: 19225558
references.citation: Kidney Int. 1976 Apr;9(4):355-62
references.pmid: 940274
references.citation: Nat Rev Nephrol. 2011 Jun 28;7(8):428-30
references.pmid: 21712850
references.citation: FASEB J. 2009 Nov;23(11):3702-11
references.pmid: 19584304
references.citation: FASEB J. 2006 Apr;20(6):720-2
references.pmid: 16436465
references.citation: N Engl J Med. 2000 May 18;342(20):1478-83
references.pmid: 10816185
references.citation: J Am Soc Nephrol. 2006 May;17(5):1305-15
references.pmid: 16597685
references.citation: N Engl J Med. 2008 Aug 7;359(6):584-92
references.pmid: 18687639
references.citation: Nephron Physiol. 2009;111(4):p59-66
references.pmid: 19339809
references.citation: J Clin Invest. 2004 Feb;113(4):561-8
references.pmid: 14966565
references.citation: Nephrol Dial Transplant. 2007 Apr;22(4):1171-6
references.pmid: 17205962
references.citation: Cardiorenal Med. 2011;1(2):102-112
references.pmid: 22258397
references.citation: Cardiorenal Med. 2011;1(1):45-52
references.pmid: 22258465
references.citation: Hypertension. 2002 Apr;39(4):838-43
references.pmid: 11967236
references.citation: Am J Kidney Dis. 2007 Mar;49(3):417-25
references.pmid: 17336703
references.citation: Kidney Int. 2010 Nov;78(10):1024-32
references.pmid: 20686451
references.citation: J Am Soc Nephrol. 2001 Oct;12(10):2131-2138
references.pmid: 11562412
references.citation: Adv Chronic Kidney Dis. 2011 Mar;18(2):98-104
references.pmid: 21406294
references.citation: Circulation. 2005 Oct 25;112(17):2627-33
references.pmid: 16246962
references.citation: Kidney Int. 2010 Feb;77(3):232-8
references.pmid: 19890272
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9805-10
references.pmid: 18606998
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19796-801
references.pmid: 18056631
references.citation: J Biol Chem. 2006 Mar 10;281(10):6120-3
references.pmid: 16436388
references.citation: J Am Soc Nephrol. 2004 Mar;15(3):770-9
references.pmid: 14978180
references.citation: Cell. 2009 Nov 25;139(5):871-90
references.pmid: 19945376
references.citation: Curr Opin Nephrol Hypertens. 2007 Jul;16(4):329-35
references.pmid: 17565275
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2331-6
references.pmid: 17287345
references.citation: Mol Pharmacol. 2009 Jul;76(1):38-46
references.pmid: 19349416
references.citation: Circ Cardiovasc Genet. 2009 Dec;2(6):583-90
references.pmid: 20031638
references.citation: Am J Kidney Dis. 2011 Jul;58(1):127-34
references.pmid: 21496980
references.citation: FASEB J. 2010 Sep;24(9):3438-50
references.pmid: 20466874
references.citation: Am J Physiol Renal Physiol. 2005 Jul;289(1):F8-28
references.pmid: 15951480
references.citation: Kidney Int. 2010 Dec;78(12):1240-51
references.pmid: 20861825
references.citation: Nature. 2006 Dec 7;444(7120):770-4
references.pmid: 17086194
references.citation: J Am Soc Nephrol. 2011 Jan;22(1):124-36
references.pmid: 21115613
references.citation: Science. 2005 Oct 21;310(5747):490-3
references.pmid: 16239475
references.citation: Curr Opin Nephrol Hypertens. 2006 Jul;15(4):437-41
references.pmid: 16775459
references.citation: J Clin Invest. 2008 Dec;118(12):3820-8
references.pmid: 19033649
references.citation: Kidney Int. 2004 Jan;65(1):1-14
references.pmid: 14675031
references.citation: J Am Soc Nephrol. 2005 Feb;16(2):520-8
references.pmid: 15615819
references.citation: Eur J Clin Nutr. 2006 Jun;60(6):734-9
references.pmid: 16391583
references.citation: Clin J Am Soc Nephrol. 2007 Nov;2(6):1283-305
references.pmid: 17942777
references.citation: Science. 2005 Sep 16;309(5742):1829-33
references.pmid: 16123266
references.citation: Kidney Int. 2008 Aug;74(3):276-88
references.pmid: 17568787
references.citation: Mol Endocrinol. 2003 Dec;17(12):2393-403
references.pmid: 14528024
references.citation: J Am Coll Cardiol. 2002 Feb 20;39(4):695-701
references.pmid: 11849871
references.citation: J Pathol. 2007 Jan;211(2):198-205
references.pmid: 17200944
references.citation: J Am Soc Nephrol. 2009 May;20(5):955-60
references.pmid: 19357251