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Vol. 34. Núm. 1.Enero 2014
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Vol. 34. Núm. 1.Enero 2014
Páginas 0-138
DOI: 10.3265/Nefrologia.pre2013.Dec.12385
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Partículas de calciproteínas (PCP): ¿verdaderas culpables de los problemas causados por el fósforo?
Calciprotein particle (CPP): a true culprit of phosphorus woes?
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7478
Makoto Kuro-oa
a Center for Molecular Medicine. Jichi Medial University, Shimotsuke, Tochigi (Japan), Department of Pathology, Center for Mineral Metabolism, University of Texas Southwestern Medical Center, Dallas, Texas, U.S.A.,
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El fosfato no goza de buena reputación entre los nefrólogos. Se asocia con la calcificación vascular y con una gran mortalidad cuando sus niveles en sangre son elevados. Provoca daños en las células endoteliales vasculares y transformación osteoblástica en las células de los músculos lisos vasculares en cultivos. Aunque muchos de los resultados adversos en los pacientes con enfermedad renal crónica (ERC) se atribuyen al fosfato, se desconoce el mecanismo molecular preciso que hay detrás de los problemas que causa. Este déficit de conocimiento ha limitado las opciones terapéuticas a la restricción del fosfato en la dieta, a captores del fosfato y a la eliminación forzada del fosfato a través de diálisis. El objetivo de esta revisión es llamar la atención de los nefrólogos sobre un metabolito del fosfato denominado partículas de calciproteínas (PCP). Se está discutiendo la posibilidad de las PCP como patógeno y nuevo objetivo terapéutico de la ERC.

Palabras clave:
Captores del fosfato
Palabras clave:
Calcificación vascular
Palabras clave:
Fetuina A
Palabras clave:
Enfermedad renal crónica (ERC)
Palabras clave:
Partículas de calciproteínas (PCP)

Phosphate is a “bad guy” among nephrologists. Phosphate is associated with vascular calcification and high mortality when it is elevated in the blood. It induces damages to vascular endothelial cells and osteoblastic transformation in vascular smooth muscle cells in culture. Although people believe that many adverse outcomes in patients with chronic kidney disease (CKD) are attributed to phosphate, nobody knows the precise molecular mechanism behind these phosphate woes. This knowledge gap has limited therapeutic options to dietary phosphate restriction, phosphate binders, and forced removal of phosphate by dialysis. The purpose of this review is to call nephrologists’ attention to a phosphate metabolite termed calciprotein particles (CPPs). The possibility of CPPs as a pathogen and a novel therapeutic target of CKD is discussed.

Keywords:
Phosphate binders
Keywords:
Vascular calcification
Keywords:
Fetuin-A
Keywords:
Chronic kidney disease (CKD)
Keywords:
Calciprotein particles (CPPs)
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Bibliografía
[1]
Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 2005;16:520-8. [Pubmed]
[2]
Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001;12:2131-8.
[3]
Martin KJ, Gonzalez EA. 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 2011;6:440-6. [Pubmed]
[4]
Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, et al. Prevalence of chronic kidney disease in the United States. JAMA 2007;298:2038-47. [Pubmed]
[5]
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;71:31-8.
[6]
Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G; Cholesterol And Recurrent Events Trial Investigators. Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 2005;112:2627-33. [Pubmed]
[7]
Block GA, Wheeler DC, Persky MS, Kestenbaum B, Ketteler M, Spiegel DM, et al. Effects of phosphate binders in moderate CKD. J Am Soc Nephrol 2012;23:1407-15.
[8]
Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002;62:245-52. [Pubmed]
[9]
Block GA, Spiegel DM, Ehrlich J, Mehta R, Lindbergh J, Dreisbach A, et al. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 2005;68:1815-24. [Pubmed]
[10]
Zhang Q, Li M, Lu Y, Li H, Gu Y, Hao C, et al. Meta-analysis comparing sevelamer and calcium-based phosphate binders on cardiovascular calcification in hemodialysis patients. Nephron Clin Pract 2010;115:c259-67. [Pubmed]
[11]
Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int 2007;71:438-41. [Pubmed]
[12]
Suki WN, Zabaneh R, Cangiano JL, Reed J, Fischer D, Garrett L, et al. Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney Int 2007;72:1130-7. [Pubmed]
[13]
Di Iorio B, Bellasi A, Russo D; INDEPENDENT Study Investigators. Mortality in kidney disease patients treated with phosphate binders: a randomized study. Clin J Am Soc Nephrol 2012;7:487-93. [Pubmed]
[14]
14 Hill KM, Martin BR, Wastney ME, McCabe GP, Moe SM, Weaver CM, et al. Oral calcium carbonate a ffects calcium but not phosphorus balance in stage 3-4 chronic kidney disease. Kidney Int 2013;83:959-66. [Pubmed]
[15]
Kuro-o M. Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism. Nat Rev Nephrol 2013;9:650-60. [Pubmed]
[16]
Heiss A, DuChesne A, Denecke B, Gr??tzinger J, Yamamoto K, Renn?? T, et al. Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem 2003;278:13333-41. [Pubmed]
[17]
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 2007;2:16-20. [Pubmed]
[18]
Rochette CN, Rosenfeldt S, Heiss A, Narayanan T, Ballauff M, Jahnen-Dechent W. 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 2009;10:735-40. [Pubmed]
[19]
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 2010;99:3986-95. [Pubmed]
[20]
Hamano T, Matsui I, Mikami S, Tomida K, Fujii N, Imai E, et al. Fetuin-mineral complex reflects extraosseous calcification stress in CKD. J Am Soc Nephrol 2010;21:1998-2007. [Pubmed]
[21]
Smith ER, Ford ML, Tomlinson LA, Rajkumar C, McMahon LP, Holt SG. Phosphorylated fetuin-A-containing calciprotein particles are associated with aortic stiffness and a procalcific milieu in patients with pre-dialysis CKD. Nephrol Dial Transplant 2012;27:1957-66. [Pubmed]
[22]
Di Marco GS, Hausberg M, Hillebrand U, Rustemeyer P, Wittkowski W, Lang D, et al. Increased inorganic phosphate induces human endothelial cell apoptosis in vitro. Am J Physiol Renal Physiol 2008;294:F1381-7. [Pubmed]
[23]
Shuto E, Taketani Y, Tanaka R, Harada N, Isshiki M, Sato M, et al. Dietary phosphorus acutely impairs endothelial function. J Am Soc Nephrol 2009;20:1504-12. [Pubmed]
[24]
Steitz SA, Speer MY, Curinga G, Yang HY, Haynes P, Aebersold R, et al. Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res 2001;89:1147-54. [Pubmed]
[25]
Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, et al. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 2000;87:E10-7. [Pubmed]
[26]
Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, 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 2004;15:2857-67. [Pubmed]
[27]
Sage AP, Lu J, Tintut Y, Demer LL. Hyperphosphatemia-induced nanocrystals upregulate the expression of bone morphogenetic protein-2 and osteopontin genes in mouse smooth muscle cells in vitro. Kidney Int 2011;79:414-22. [Pubmed]
[28]
Villa-Bellosta R, Sorribas V. Phosphonoformic acid prevents vascular smooth muscle cell calcification by inhibiting calcium-phosphate deposition. Arterioscler Thromb Vasc Biol 2009;29:761-6. [Pubmed]
[29]
Ewence AE, Bootman M, Roderick HL, Skepper JN, McCarthy G, Epple M, et al. Calcium phosphate crystals induce cell death in human vascular smooth muscle cells: a potential mechanism in atherosclerotic plaque destabilization. Circ Res 2008;103:e28-34. [Pubmed]
[30]
Pasch A, Farese S, Gr??ber S, Wald J, Richtering W, Floege J, et al. Nanoparticle-based test measures overall propensity for calcification in serum. J Am Soc Nephrol 2012;23:1744-52. [Pubmed]
[31]
Smith ER, Ford ML, Tomlinson LA, Bodenham E, McMahon LP, Farese S, et al. Serum Calcification Propensity Predicts All-Cause Mortality in Predialysis CKD. J Am Soc Nephrol 2013 Oct 31. [Epub ahead of print]
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Nefrología

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