Calciprotein particle (CPP): a true culprit of phosphorus woes?

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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "1" "paginaFinal" => "4" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Makoto Kuro-o" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Makoto" "apellidos" => "Kuro-o" "email" => array:1 [ 0 => "makoto.kuro-o@utsouthwestern.edu" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "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., " "etiqueta" => "a" "identificador" => "affa" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Partículas de calciproteínas (PCP): ¿verdaderas culpables de los problemas causados por el fósforo?" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12385_19904_53741_en_12385_f1.jpg" "Alto" => 430 "Ancho" => 600 "Tamanyo" => 144026 ] ] "descripcion" => array:1 [ "en" => "Calciprotein particle." ] ] ] "textoCompleto" => "Since hyperphosphatemia was identified as a potent mortality risk,1,2 phosphate binders have been prescribed for CKD patients to lower serum phosphate levels, and have indeed improved their clinical outcomes.3 Because serum phosphate levels stay within normal range until CKD advances to stage 4-5, the use of phosphate binders is justified for end-stage renal disease (ESRD), which accounts only for a few percent of total CKD patients.4,5 However, all-cause mortality is known to correlate positively with serum phosphate levels even when they are within normal range.6 These observations have evoked a fierce debate on whether or not indication of phosphate binders should be expanded from ESRD to moderate CKD patients in order to further lower their normal serum phosphate levels.Several clinical studies have been performed to determine whether or not phosphate binders are beneficial for moderate CKD. Block et al. reported a prospective randomized study of 148 CKD patients at stage 3-4 to determine the effect of three different phosphate binders on vascular calcification.7 The result was somewhat unexpected: Phosphate binders rather accelerated vascular calcification. However, when the effect of different binders (calcium acetate, lanthanum carbonate, and sevelamer carbonate) was analyzed separately, calcium acetate was found primarily responsible for the adverse outcome, whereas the other calcium-free binders were not statistically different from placebo, at least in the small number of patients treated for up to 9 months. Further studies are necessary to conclude that phosphate binders are not beneficial for moderate CKD. Of note, several other studies found advantage of calcium-free binders over calcium-containing binders in suppressing vascular calcification and all-cause mortality in dialysis patients as well as stage 3-4 non-dialysis CKD patients.8-13 This may be because calcium-containing binders cause calcium overload, which may contribute to vascular calcification. In fact, Hill et al. reported that calcium carbonate induced positive calcium balance in stage 3-4 CKD patients.14How can all these observations be reconciled? Why is phosphate harmful and how does calcium affect the phosphate woes? As a plausible hypothesis that potentially addresses these questions, I have proposed that cardiovascular complications in CKD are triggered by a pathogen called CPP.15What is CPP? CPP stands for calciprotein particles, which are nanoparticles composed of calcium-phosphate (CaP) crystals and mineral binding proteins such as Fetuin-A. The process of CPP formation has been studied extensively in vitro.16-19 When concentration of calcium and phosphate exceeds the solubility limit, insoluble CaP crystals are generated instantaneously. They can grow over time and eventually precipitate as hydroxyapatite. However, CaP crystals do not grow in the blood, because serum protein Fetuin-A absorbs CaP crystals and prevents them from growing into large precipitates. The CaP crystal-laden Fetuin-A molecules aggregate to form nanoparticles or CPP (Figure 1). Because CPPs are nanoparticles, they are dispersed in the serum as colloid particles and not precipitated. Thus, formation of CPP can be regarded as a defense mechanism that prevents blood vessels from being occluded with insoluble CaP precipitates. Solubilizing insoluble substance as colloid particles using its binding protein is a universal strategy typically seen in lipoporteins.Recent studies have indicated that CPPs appear in the blood of CKD patients.20,21 In these studies, serum CPP levels were measured by a “sequential centrifugation” method: First, clotted blood was centrifuged at 3,000 x g for 10 minutes to harvest serum. Because CPPs are colloid particles, they never precipitate under this condition and stay in the serum. Next, the serum was centrifuged at a higher speed (16,000-22,000 x g) for a longer time (2 hours) to precipitate CPPs. They measured serum Fetuin-A concentration by ELISA before and after the high-speed centrifugation and assumed that the difference of Fetuin-A concentration between the two represented the serum CPP level (Figure 2). These studies have shown that serum CPP levels were positively correlated with coronary calcification score20 and independently associated with serum phosphate, inflammation (high-sensitive CRP), procalcific factors (oxidized LDL and BMP-2/7 ratio), arterial stiffness (aortic pulse wave velocity), and decline of renal function (eGFR).21 Importantly, many of these findings were observed in stage 3-4 CKD patients whose serum phosphate levels were within normal range.On the other hand, numerous basic studies have described the effect of high extracellular phosphate on various types of cells in culture. When phosphate was added to the tissue culture medium, oxidative stress and cell death were induced in vascular endothelial cells.22,23 In vascular smooth muscle cells, phosphate induced phenotypic transition into osteoblastic cells, which was associated with induction of bone-related gene expression including BMP-2, RUNX2, and osteopontin.24,25 These cellular responses to high extracellular phosphate, if occurred in vivo, may explain vascular calcification in ESRD.26 However, it should be noted that phosphate and calcium concentration in regular tissue culture media like DMEM is about 1mM and 2mM, respectively, which is close to the solubility limit. Thus, a small increase in phosphate or calcium concentration potentially triggers formation of CaP crystals and, in the presence of serum, leads to formation of CPPs. Thus, it is possible that the effect of phosphate on cultured cells may actually be attributed to CaP crystals or CPPs but not to phosphate itself. In fact, some studies tested this possibility and demonstrated that this was indeed the case: Phosphate failed to induce those cellular responses when formation of CaP crystals was blocked with pyrophosphate or phosphonoformic acid.27-29Taken together, a plausible scenario is that serum CPPs function as a ligand that triggers damages in vascular endothelial cells and osteoblastic transition in vascular smooth muscle cells, thereby leading to vascular calcification in CKD. In other words, CPP may be regarded as an endogenous “pathogen” that circulates in the blood and causes vascular calcification. Because serum CPP levels can be high even when serum phosphate levels are within normal range,21 this hypothesis explains why vascular calcification occurs in CKD patients whose serum phosphate levels are not elevated. It also explains why calcium-free binders tend to be more beneficial than calcium-containing binders.Many questions must be addressed before this “CPP theory of CKD” is verified: Where do serum CPPs come from? The fact that CPPs are found in the serum of CKD patients with normal serum calcium and phosphate levels has raised the possibility that formation of CaP crystals (nucleation) may not necessarily take place in situ in the blood. It is possible that CaP crystals generated somewhere else may enter the blood stream and bind to Fetuin-A to become CPPs. Then, where is the place of nucleation and why is nucleation accelerated in CKD patients? Obviously it is of critical importance to identify the cell-surface receptor for CPPs. If these questions are addressed and the CPP theory of CKD is verified, CPP may be justified as a diagnostic marker for vascular calcification in CKD. Recently, a new assay was reported, which measured a physical property of serum CPPs as colloid particles in vitro to determine the overall calcification propensity of serum.30 In fact, the result of this assay was independently associated with aortic stiffness and mortality.31 In addition, CPP may be justified as a novel therapeutic target. Suppression of CPP formation or action by inhibitors for CaP crystal formation or putative CPP receptor may become a novel strategy for the treatment of CKD. Conflict of interest The authors declare that there is no conflict of interest associated with this manuscript.<a href="grande/12385_19904_53741_en_12385_f1.jpg" class="elsevierStyleCrossRefs"><img src="12385_19904_53741_en_12385_f1.jpg" alt="Calciprotein particle."></img></a>Figure 1. Calciprotein particle.<a href="grande/12385_19904_53743_en_12385_f2.jpg" class="elsevierStyleCrossRefs"><img src="12385_19904_53743_en_12385_f2.jpg" alt="Measurement of the serum CPP level."></img></a>Figure 2. Measurement of the serum CPP level." "pdfFichero" => "P1-E565-S4487-A12385-EN.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "es" => array:5 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec439015" "palabras" => array:1 [ 0 => "Captores del fosfato" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec439017" "palabras" => array:1 [ 0 => "Calcificación vascular" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec439019" "palabras" => array:1 [ 0 => "Fetuina A" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec439021" "palabras" => array:1 [ 0 => "Enfermedad renal crónica (ERC)" ] ] 4 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec439023" "palabras" => array:1 [ 0 => "Partículas de calciproteínas (PCP)" ] ] ] "en" => array:5 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439016" "palabras" => array:1 [ 0 => "Phosphate binders" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439018" "palabras" => array:1 [ 0 => "Vascular calcification" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439020" "palabras" => array:1 [ 0 => "Fetuin-A" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439022" "palabras" => array:1 [ 0 => "Chronic kidney disease (CKD)" ] ] 4 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439024" "palabras" => array:1 [ 0 => "Calciprotein particles (CPPs)" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "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." ] "en" => array:1 [ "resumen" => "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." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12385_19904_53741_en_12385_f1.jpg" "Alto" => 430 "Ancho" => 600 "Tamanyo" => 144026 ] ] "descripcion" => array:1 [ "en" => "Calciprotein particle." ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12385_19904_53743_en_12385_f2.jpg" "Alto" => 285 "Ancho" => 600 "Tamanyo" => 77604 ] ] "descripcion" => array:1 [ "en" => "Measurement of the serum CPP level." ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15615819" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21292848" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17986697" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16246962" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002;62:245-52. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12081584" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16164659" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20424476" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17200680" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17728707" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/22241819" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/23254903" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Kuro-o M. Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism. Nat Rev Nephrol 2013;9:650-60. <a href="http://www.ncbi.nlm.nih.gov/pubmed/23774819" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Heiss A, DuChesne A, Denecke B, Grötzinger J, Yamamoto K, Renné 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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12556469" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20408632" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19222044" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21156141" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20947626" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/22105144" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 21 => array:3 [ "identificador" => "bib22" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18385273" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 22 => array:3 [ "identificador" => "bib23" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19406976" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 23 => array:3 [ "identificador" => "bib24" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11739279" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 24 => array:3 [ "identificador" => "bib25" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11009570" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 25 => array:3 [ "identificador" => "bib26" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15504939" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 26 => array:3 [ "identificador" => "bib27" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20944546" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 27 => array:3 [ "identificador" => "bib28" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19213941" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 28 => array:3 [ "identificador" => "bib29" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18669918" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 29 => array:3 [ "identificador" => "bib30" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Pasch A, Farese S, Gräber 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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/22956818" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 30 => array:3 [ "identificador" => "bib31" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "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]" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003400000001/v0_201502091619/X2013251414053697/v0_201502091619/en/main.assets" "Apartado" => array:4 [ "identificador" => "35445" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Short Reviews" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003400000001/v0_201502091619/X2013251414053697/v0_201502091619/en/P1-E565-S4487-A12385-EN.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251414053697?idApp=UINPBA000064"]