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.
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.
PAIDI CTS179 Scientific group: Clinical Medicine
- mineral metabolism
- parathyroid glands
- vascular calcification
- renal failure
- bone mineral disease
- mesenchymal stem cells
- Wnt / beta-catenin
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.
- Magnesio potencia la diferenciación de células madre mesenquimales
Owner: Fresenius Medical Care, S.A.
Application nr: 14009
- 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
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
Registry date: 04/12/2012
Approval date: 04/12/2012
- I Award Abbot of research of Bone Metabolism in Renal Insufficiency 1996
- X Edition Award Iñigo Alvarez de Toledo 1998 (Fundación Renal)
- PENSA 2000 (ESTEVE) award for research project
- Best paper in nefrology in 1999 in the journal "Nefrología e hipertensao"
- XVI Premio Janssen-Cilag Best poster presented at the XXXIV SEN National Congress
- IX National Research award 2011 (Colegio de médicos de Córdoba)
- II IMIBIC 2012 Awards for relevant scientific publications in 2011
- III IMIBIC 2013 Awards for relevant scientific publications in 2012
- Janssen-Cilag-SENEFRO 2013 best publication in basic research in nefrology
- SEN SENEFRO 2013 Best poster presented at XLIII SEN Annual Congress (Sociedad Española de Nefrolofia)
- XIV Edition National Award (Colegio de Médicos de Córdoba). 2º prize, category best publication.
- II Innovation Prize Roche-IMIBIC (IMIBIC, Roche) 2015
- VIII Prize for Business ideas (University of Cordoba) 2015