The Calcium metabolism. Vascular calcification research group is a consolidated group of IMIBIC, bringing together both basic and clinical researchers in various scientific disciplines, such as medicine, biology and veterinary medicine, and it include also nursing, technical and administrative staff.
Our research group is focused on different aspects of calcium metabolism and vascular calcification. Our primary area of research is the study of the pathogenetic mechanisms of secondary hyperparathyroidism associated with renal failure. We study the parathyroid function, both at cellular and molecular level (PTH synthesis and secretion and cell proliferation) of normal and hyperplastic parathyroid glands. More recently we have also embarked on research of in vivo and in vitro mechanisms of vascular calcification. In addition, we are interested in studying biomarkers of renal disease progression as well as the bone alterations promoted during chronic kidney disease.
The main aim of our research group is to go deeper into the mechanisms that promote vascular calcifications and the progression of renal disease and to propose new therapeutic alternatives leading to improved renal health of the patients. Results derived from our research may lead to the proposal and use of new therapeutic targets for preventing and reversing vascular calcification and associated complications.
In the last year, our research group has published some important manuscripts that are contributing to our understanding about the alterations of mineral metabolism during renal disease. We are identifying new biomarkers of renal disease progression and contributing new mechanisms of vascular calcification and mineral bone disease. Recently we are working in clinical investigation lines, performing independent clinical trials in patients with chronic kidney disease.
The Principal Investigator of the group Juan Mariano Rodriguez Portillo acts as collaborator in both the Spanish Renal Research Network (REDinREN) and the PAIDI CTS-179 Scientific group. Other collaborations include highly competitive research groups both on national and international level, as well as companies of pharmaceutical industry.
Líneas de Investigación
In the context of vascular calcification, our groups has recently incorporated into our research activities both in vivo (experimental models with rats) and in vitro studies (vascular smooth muscle cells) of the mechanisms underlying the development of vascular calcification in chronic kidney disease. Thus, in the context of vascular calcification we analyze the role of different diets (with different contents of phosphorus, calcitriol, micronutrients such as magnesium or calcium, calorie diets...) on uremia and vascular calcification. We are also interested in the evaluation of the involvement of bone marrow mesenchymal stem cells in vascular calcification. Based on a stem cell-based approach, we analyze the signaling pathways by which vascular calcification progresses.
In this line, and of particular interest, is the research we conduct with new phosphate binders and the study on vascular calcification.
Recently we have also incorporated a new line of research to evaluate the interaction between microbiota, vascular calcification and chronic kidney disease alterations.
We are performing clinical trials with different types of uremic patients to evaluate the use of phosphaturia as biomarker of renal disease progression and serum FGF23 levels as biomarker of vascular damage associated to chronic kidney disease. We try also to evaluate if the phosphate binder use previous to hyperphosphatemia may be useful to delay the associated complications to chronic kidney disease.
We use experimental animal models and in vitro cultures to analyze the role of altered elements during uremia on vascular calcification process. For example, we are interested in the analysis of the effects of high phosphate concentrations as inductor of inflammation, oxidative stress and renal injury.
Within this line of research, we will study the relationship between Klotho, sclerostin and other bone mineral metabolism parameters as biomarkers of vascular calcification.
During the end stage of chronic kidney disease it is very usual that mineral metabolism disbalance leads to bone mineral disease as renal osteodystrophy. At the moment, the cause of these bone alterations is attributed mainly to changes in PTH levels. Our group’s studies in this area aim at gaining new knowledge concerning these bone alteration as well as to understand how the different elements of mineral metabolism participate in the renal osteodystrophy. We are performing studies about the role of FGF23, Mg supplements, calcitriol, phosphorous or calcimimetics on bone histomorphometry. In addition, we are analyzing the role of the different intracellular signaling pathways such as Wnt/b-catenin, Nocth, Erk, epigenetic modifications, inflammation etc. on osteogenesis and osteoclastogenesis. Mesenchymal stem cells are also being used to study how the chronic kidney disease or its treatments may affect bone regarding the formation of new osteoblasts and osteoclasts.
Networks
REDinREN - Spanish Renal Research Network
EUTOX - European Uremic Toxic Work Group
ERA-EDTA - CKD-MBD GROUP
PAIDI CTS-179 - Medical Clinic
Palabras Clave
- calcium
- phosphorus
- mineral metabolism
- parathyroid glands
- PTH
- calcification
- uremia
- HPTH2º
- vascular calcification
- renal failure
- bone mineral disease
- VDR
- CaSR
- mesenchymal stem cells
- Wnt / beta-catenin
- FGF23
Información Adicional
Highlighted publications
Rodríguez-Ortiz ME, Pontillo C, Rodríguez M, Zürbig P, Mischak H, Ortiz A. Novel Urinary Biomarkers For Improved Prediction Of Progressive Egfr Loss In Early Chronic Kidney Disease Stages And In High Risk Individuals Without Chronic Kidney Disease. Sci Rep. 2018 Oct 29;8(1):15940. doi: 10.1038/s41598-018-34386-8. Erratum in: Sci Rep. 2018 Dec 10;8(1):17822. PubMed PMID: 30374033; PubMed Central PMCID: PMC6206033.
Pineda C, Rios R, Raya AI, Rodriguez M, Aguilera-Tejero E, Lopez I. Hypocaloric Diet Prevents the Decrease in FGF21 Elicited by High Phosphorus Intake. Nutrients. 2018 Oct 13;10(10). pii: E1496. doi: 10.3390/nu10101496. PubMed PMID: 30322116; PubMed Central PMCID: PMC6213303.
Santamaría R, Díaz-Tocados JM, Pendón-Ruiz de Mier MV, Robles A, Salmerón-Rodríguez MD, Ruiz E, Vergara N, Aguilera-Tejero E, Raya A, Ortega R, Felsenfeld A, Muñoz-Castañeda JR, Martín-Malo A, Aljama P, Rodríguez M. Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms. Sci Rep. 2018 Sep 12;8(1):13701. doi: 10.1038/s41598-018-32065-2. PubMed PMID: 30209259; PubMed Central PMCID: PMC6135842.
Rodelo-Haad C, Rodríguez-Ortiz ME, Martin-Malo A, Pendon-Ruiz de Mier MV, Agüera ML, Muñoz-Castañeda JR, Soriano S, Caravaca F, Alvarez-Lara MA, Felsenfeld A, Aljama P, Rodriguez M. Phosphate control in reducing FGF23 levels in hemodialysis patients. PLoS One. 2018 Aug 7;13(8):e0201537. doi: 10.1371/journal.pone.0201537. eCollection 2018. PubMed PMID: 30086150; PubMed Central PMCID: PMC6080760.
Rios R, Pineda C, Lopez I, Muñoz-Castañeda J, Rodriguez M, Aguilera-Tejero E, Raya AI. Phosphorus restriction does not prevent the increase in fibroblast growth factor 23 elicited by high fat diet. PLoS One. 2018 Jun 1;13(6):e0198481. doi: 10.1371/journal.pone.0198481. eCollection 2018. PubMed PMID: 29856857; PubMed Central PMCID: PMC5983526.
Patents
Magnesio potencia la diferenciación de células madre mesenquimales
Owner: Fresenius Medical Care, S.A.
Application nr: 14009
Country: Germany
Date: 14/01/2014
Use of platelet derived growth factor for the treatment of vascular calcifications
Authors: María Encarnación Rodríguez Ortiz, Carmen María Herencia Bellido, Yolanda Almadén Peña, Juan Mariano Rodríguez Portillo, Antonio Canalejo Raya, Juan Rafael Muñoz Castañeda, Julio Manuel Martínez Moreno
Owner: Gerencia Provincial del Servicio Andaluz de Salud
Application nr: P201231884
Country: Spain
Registry date: 03/12/2012
Approval date: 03/01/2013
Use of a selective agonist of at2 receptor for the treatments of vascular calcifications
Authors: Yolanda Almadén Peña, Juan Mariano Rodríguez Portillo, Antonio Canalejo Raya, Juan Rafael Muñoz Castañeda, Carmen María Herencia Bellido, María Encarnación
Rodríguez Ortiz, Julio Manuel Martínez Moreno
Owner: Gerencia Provincial del Servicio Andaluz de Salud
Application nr: P201231890
Country: Spain
Registry date: 04/12/2012
Approval date: 04/12/2012
Awards
I Premio Abbot de Investigación sobre Metabolismo óseo en la Insuficiencia Renal 1996. Título: Efecto directo del fosforo sobre la síntesis y secreción de PTH, y sobre la división celular en la glándula paratiroides. Autores: A. Hernández, Y. Almadén, A. Canalejo, V. Torregrosa, J.M. Campistol, E. Salido, A. Torres y M. Rodríguez.
X Edición Premio Iñigo Alvarez de Toledo (1998), de la Fundación Renal, a la Investigación Aplicada o Clínica. Título: Factores implicados en la pérdida de masa ósea y en el hiperparatiroidismo persistente tras el transplante renal. Autores: A. Torres, V. Torregrosa, J.M. Campistol, J. Barrios, Y. Almadén, A. Hernández, S. García Rebollo, A. Canalejo, A. González, M. Machado, M.A. Gómez, V. Lorenzo, A. Rodríguez, D. Hernández, E. Salido, M. Rodríguez.
Premio PENSA 2000 (Grupo ESTEVE) al proyecto de investigación. titulado: Regulación de la expresión génica de calcitriol (vdr) y de calcio (Rca) en el hiperparatiroidismo secundario. Autores: A. Canalejo, Y. Almadén, F. Luque, B. Garfia, S. Cañadillas, M. Rodríguez.
Premio de la Sociedad Portuguesa de Nefrología al mejor artículo de revisión del año 1999 en la revista portuguesa de Nefrología e hipertensao. Título del trabajo: la importancia del fósforo en la patogénesis del hiperparatiroidismo secundario. Autores: A. Canalejo, Y. Almadén, G. Añón, M. Rodríguez.
XVI Premio Janssen-Cilag al mejor poster presentado en el XXXIV Congreso Nacional de la S.E.N. (2004). Título: Utilidad de la combinación de calcitriol con el calcimimético NPSR-568 en el control del hiperparatiroidismo secundario. Efecto sobre calcificación vascular.
IX Premio Nacional de Investigación del colegio de médicos de Córdoba. 2011. Título: Fgf23 fail to inhibit uremic parathyroid glands.
II Convocatoria 2012 Premios a la publicaciones científicas relevantes 2011. Premio a la publicación, con filiación y autoría principal por parte del IMIBIC, con la colaboración con varios grupos internacionales al trabajo titulado Direct and indirect effect of parathyroid on circulating levels of fibroblast growth factor 23 in vivo. Autores: ILópez, ME Rodriguez- Ortiz, Y. Almadén, F. Guerrero, A. Montes de Oca, C. Pineda, V. Shalhoub, M.Rodriguez, E. Aguilera-Tejero.
III Convocatoria IMIBIC 2013 Premios a la publicaciones científicas relevantes 2012. Premio a la publicación, con filiación y autoría principal por parte del IMIBIC, con la colaboración con varios grupos internacionales al trabajo titulado Calcium deficiency reduces circulating levels of FGF23. Autores: Rodriguez-Ortiz ME, Lopez I, Muñoz-Castañeda JR, Martinez-Moreno JM, Ramírez AP, Pineda C, Canalejo A, Jaeger P, Aguilera-Tejero E, Rodriguez M, Felsenfeld A, Almaden Y.
Premio Janssen-Cilag-SENEFRO 2013 al mejor trabajo publicado en Nefrología Básica al trabajo titulado Calcium deficiency reduces circulating levels of FGF23. Autores: Rodriguez-Ortiz ME, Lopez I, Muñoz-Castañeda JR, Martinez-Moreno JM, Ramírez AP, Pineda C, Canalejo A, Jaeger P, Aguilera-Tejero E, Rodriguez M, Felsenfeld A, AlmadenY. (J Am Soc Nephrol. 23(7):1190-7, 2012).
Descripción: Premio SEN SENEFRO 2013 al mejor poster presentado en el XLIII Congreso Anual de la SEN al trabajo titulado Magnesium modulates parathyroid hormone secretion and upregulates parathyroidreceptor expressions at moderately low calcium concentration.Autores: Rodríguez-Ortiz ME, Canalejo A,Herencia C, Martínez-Moreno JM, Peralta-Ramírez A, Perez-Martinez P, Navarro-González JF, Rodríguez M, Peter M, Gundlach K, Steppan S, Passlick-Deetjen J, Muñoz-Castañeda JR, Almaden Y.
XIV Edición Nacional Premios Colegios de Médicos de Córdoba.1 Diciembre 2016. 2º premio obtenido a la publicación High phosphate induces a pro-inflammatory response by vascular smooth muscle cells and modulation by vitamin D derivatives. Martínez-Moreno JM, Herencia C, de Oca AM, Díaz-Tocados JM, Vergara N, Gómez-Luna MJ, López-Argüello SD, Camargo A, Peralbo-Santaella E, Rodríguez-Ortiz ME, Canalejo A, Rodríguez M, Muñoz-Castañeda JR, Almadén Y.Clin Sci (Lond). 2017 Jun 28;131(13):1449-1463.
II Premio de Innovación Biomédica Roche-IMIBIC. 2015.
VIII Premio Ideas de Negocio, Universidad de Córdoba. 2015.
Premio IMIBIC 2012 a la mejor publicación con la colaboración de varios grupos internacionales: “Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo”.
Premio IMIBIC 2013 a la publicación científica más relevante en colaboración con grupos internacionales: “Calcium deficiency reduces circulating levels of FGF23”.
Premio a la mejor comunicación oral en el XLV Congreso de la Sociedad Andaluza de Nefrología: “Factores relacionados con el incremento de FGF23 en pacientes en hemodiálisis”. 2017.
Premio a la mejor comunicación tipo póster de la Sesión “Chronic and Inflammatory, and Cancer” de las VIII Jornadas de Jóvenes Investigadores del IMIBIC: “Serum phosphate modifications are associated with changes in serum fgf23 and c-reactive protein”. 2017.
Premio a la mejor comunicación oral de la sesión “Chronic and Inflammatory Diseases” de las IX Jornadas de Jóvenes Investigadores del IMIBIC: “Effect of magnesium on the processes of inflammation and oxidative stress associated with chronic kidney disease”. 2018.
Premio “Enrique Aguilar Benítez de Lugo a la publicación científica más relevante” por el trabajo “Dietary magnesium supplementation prevents and reverses vascular and soft tissue calcification in uremic rats”. 2018.
