Research groups

GC13 Calcium metabolism. Vascular calcification

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.

Research Lines

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

Keywords

  • 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

Additional Information

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 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
     

GC13 Calcium metabolism. Vascular calcification

Principal Investigator
Mariano Rodríguez Portillo

Emerging Researcher
Juan Rafael Muñoz Castañeda

Researchers
Escolástico Aguilera Tejera
Antonio Luis Canalejo Raya
Ignacio López Villalba

Post-Doctoral Researchers
Carmen María Pineda Martos
Ana Isabel Raya Bermúdez
María Encarnación Rodríguez Ortiz

Clinical Researchers
Cristian Rodelo Haad

Pre-Doctoral Researchers
Juan Miguel Díaz Tocados
Rodrigo López Baltanás
María Victoria Pendón Ruiz de Mier
Rafael Ríos Varo
Noemi Vergara Segura

Administrative and Technical Staff
Sandra García Valdivia
Alicia Andújar Gil
Cristina Membrives González
Erena Ruiz Mora

Projects

Active Projects

Regional

Rodríguez Ortiz, Mª.E. Characterization of Wnt induced changes by Mg and sclerotine and its repercussion in the mineral, bone and vascular disorders associated with chronic kidney disease. Funding Agency: Regional Ministry of Equality, Health and Social Policies (CISPS). Reference:  PI-0154-2017

National

Muñoz Castañeda, JR, Rodriguez Portillon, JM. Influence of urinary phosphorous excretion on the renal injury progression. Mechanisms and clinical studies. Funding agency: National Institute of Health Carlos III (ISCIII). Reference: PI14/00638

Muñoz Castañeda, JR. New therapy for the treatment of degenerative osteoarthrosis based on a modification of adipose-tissue-derived mesenchymal stem cells. Funding agency: National Institute of Health Carlos III Health (ISCIII). Reference: DTS16/00061                 

Rodríguez Portillo, M. Characterization of Mg and sclerotin-induced changes in Wnt and its impact on mineral, bone andvascular disorder with chronic kidney disease. Funding agency: National Institute of Health Carlos III Health (ISCIII). Reference: PI17/01010

Muñoz Castañeda, J.R.Estudios básicos y clínicos acerca de la disfunción vascular inducida por altos niveles de FGF23 en pacientes urémicos..Funding Agency: National Institute of Health Carlos III (ISCIII).Reference:PI18/00138

Publications

Main Publications 2018

Rodriguez M, Aguilera-Tejero E. Energy-Dense Diets and Mineral Metabolism in the Context of Chronic Kidney Disease-Metabolic Bone Disease (CKD-MBD). NUTRIENTS. 2018; 10(12): Núm artículo  1840
IF: 4,196  
Q: 1

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; 10(10): Núm artículo 1496
IF: 4,196  
Q: 1

Santamaria R, Diaz-Tocados JM, de Mier MVPR, Robles A, Salmeron-Rodriguez MD, Ruiz E, Vergara N, Aguilera-Tejero E, Raya A, Ortega R, Felsenfeld A, Munoz-Castaneda JR, Martin-Malo A, Aljama P, Rodriguez M. Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms. SCIENTIFIC REPORTS. 2018; 8: Núm artículo 13701
IF: 4,122  
Q: 1

Rodelo-Haad C, Rodriguez-Ortiz ME, Martin-Malo A, de Mier MVPR, Aguera ML, Munoz-Castaneda 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; 13(8):e0201537
IF: 2,766  
Q:1

Rios R, Pineda C, Lopez I, Munoz-Castaneda 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; 13(6): Núm artículo e0198481
IF: 2,766  
Q: 1

Munoz-Castaneda JR, de Mier MVPR, Rodriguez M, Rodriguez-Ortiz ME. Magnesium Replacement to Protect Cardiovascular and Kidney Damage? Lack of Prospective Clinical Trials.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2018; 19(3): Núm artículo 664
IF: 3,687  
Q:2

Other Publications 2018

Rodriguez-Ortiz ME, Pontillo C, Rodriguez M, Zurbig 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. SCIENTIFIC REPORTS. 2018; 8: Núm artículo 15940
IF: 4,122  
Q: 1

Sanchez-Gonzalez C, Gonzalez-Casaus ML, Sellares VL, Albalate M, Torregrosa JV, Mas S, Ortiz A, Rodriguez M, Gonzalez-Parra E. Higher Proportion of Non-1-84 PTH Fragments in Peritoneal Dialysis Patients Compared to Hemodialysis Patients Using Solutions Containing 1.75 mmol/l Calcium. FRONTIERS IN PHYSIOLOGY. 2018; 9: Núm artículo 1643
IF: 3,394  
Q: 1

de Mier MVPR, Aguera ML, Navarro MD, Rodriguez-Benot A, Aljama P. Prevalence and Survival of Cancer After Pancreas-Kidney Transplantation. TRANSPLANTATION PROCEEDINGS. 2018; 50(2):669-672.
IF: 0,806  
Q: 4

Rodelo-Haad C, Gimenez RFD, Ortega R, Rodriguez M, Aljama P. Calcific arteriolopathy beyond chronic kidney disease. The role of hemochromatosis and vitamin K antagonists. CLINICAL CASES IN MINERAL AND BONE METABOLISM. 2018; 15(1):85-88.
IF: 0

Main Publications 2017

Diaz-Tocados JM, Peralta-Ramirez A, Rodriguez-Ortiz ME, Raya AI, Lopez I, Pineda C, Herencia C, de Oca AM, Vergara N, Steppan S, de Mier MVPR, Buendia P, Carmona A, Carracedo J, Alcala-Diaz JF, Frazao J, Martinez-Moreno JM, Canalejo A, Felsenfeld A, Rodriguez M, Aguilera-Tejero E, Almaden Y, Munoz-Castaneda JR. Dietary magnesium supplementation prevents and reverses vascular and soft tissue calcifications in uremic rats. KIDNEY INTERNATIONAL. 2017.92(5):1084-1099.
IF: 8,395
Q: 1  D: 1

Munoz-Castaneda JR, Herencia C, de Mier MVPR, Rodriguez-Ortiz ME, Diaz-Tocados JM, Vergara N, Martinez-Moreno JM, Salmeron MD, Richards WG, Felsenfeld A, Kuro-O M, Almaden Y, Rodriguez M. Differential regulation of renal Klotho and FGFR1 in normal and uremic rats. FASEB JOURNAL. 2017.31(9):3858-3867.
IF: 5,498
Q: 1  D: 1

Martinez-Moreno JM, Herencia C, de Oca AM, Diaz-Tocados JM, Vergara N, Gomez-Luna MJ, Lopez-Arguello SD, Camargo A, Peralbo-Santaella E, Rodriguez-Ortiz ME, Canalejo A, Rodriguez M, Munoz-Castaneda JR, Almaden Y. High phosphate induces a pro-inflammatory response by vascular smooth muscle cells and modulation by vitamin D derivatives. CLINICAL SCIENCE. 2017.131(13):1449-1463.
IF: 4,936
Q: 1 

Portillo MR, Rodriguez-Ortiz ME. Secondary Hyperparthyroidism: Pathogenesis, Diagnosis, Preventive and Therapeutic Strategies. REVIEWS IN ENDOCRINE & METABOLIC DISORDERS. 2017.18(1):79-95.
IF: 4,817
Q: 1 

Diaz-Tocados JM, Herencia C, Martinez-Moreno JM, de Oca AM, Rodriguez-Ortiz ME, Vergara N, Blanco A, Steppan S, Almaden Y, Rodriguez M, Munoz-Castaneda JR. Magnesium Chloride promotes Osteogenesis through Notch signaling activation and expansion of Mesenchymal Stem Cells. SCIENTIFIC REPORTS. 2017.7(1):-7839.
IF: 4,259
Q: 1 

Acevedo LM, Raya AI, Rios R, Aguilera-Tejero E*, Rivero JLL*. Obesity-induced discrepancy between contractile and metabolic phenotypes in slow- and fast-twitch skeletal muscles of female obese Zucker rats. JOURNAL OF APPLIED PHYSIOLOGY. 2017.123(1):249-259.
IF: 3,351
Q: 1 

Acevedo LM, Raya AI, Martinez-Moreno JM, Aguilera-Tejero E*, Rivero JLL*. Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats. PLOS ONE. 2017.12(3):-e0173028.
IF: 2,806
Q: 1 

Lopez I, Pineda C, Raya AI, Rodriguez-Ortiz ME, Diaz-Tocados JM, Rios R, Rodriguez JM, Aguilera-Tejero E, Almaden Y. Leptin directly stimulates parathyroid hormone secretion. ENDOCRINE. 2017.56(3):675-678.
IF: 3,131
Q: 2 

Pineda C, Aguilera-Tejero E, Morales MC, Belinchon-Lorenzo S, Gomez-Nieto LC, Garcia P, Martinez-Moreno JM, Rodriguez-Ortiz ME, Lopez I. Treatment of canine leishmaniasis with marbofloxacin in dogs with renal disease. PLOS ONE. 2017.12(10):-e0185981.
IF: 2,806
Q: 1 

Rios R, Raya AI, Pineda C, Rodriguez M, Lopez I, Aguilera-Tejero E. Vitamin E protects against extraskeletal calcification in uremic rats fed high fat diets. BMC NEPHROLOGY. 2017.18():-.
IF: 2,289
Q: 2 

Other Publications 2017

Argiles A, Rodriguez M, Ortiz A. Is Plasma Proteomics Able to Provide Alternative Paths to Better Understand Hypertension? HYPERTENSION. 2017.70(2):250-252.
IF: 6,857
Q: 1  D: 1

Perez-del Palacio J, Diaz C, Vergara N, Algieri F, Rodriguez-Nogales A, de Pedro N, Rodriguez-Cabezas ME, Genilloud O, Galvez J, Vicente F. Exploring the Role of CYP3A4 Mediated Drug Metabolism in the Pharmacological Modulation of Nitric Oxide Production. FRONTIERS IN PHARMACOLOGY. 2017.8():-202.
IF: 4,4
Q: 1 

Clinical Research

Active in 2018

Estudio doble ciego, aleatorizado, controlado con placebo para evaluar el efecto de SNF472 en la progresión de la calcificación cardiovascular además del tratamiento de referencia en pacientes con nefropatía terminal (NT) sometidos a hemodiálisis (HD).
PI: Dr Rodríguez Portillo, J. Mariano

Open phase II clinical trial for assessment of the effectiveness of the decrease of intestinal absorption of phosphorous in the progression of kidney disease in patients with metabolic syndrome
PI: Dr Rodríguez Portillo, J. Mariano

Non-interventionist study for the safety, effectiveness and adherence of Velphoro in the short and long term in the real life of patients with hyperphosphatemia subjected to hemodialysis or peritoneal dialysis.
PI: Dr Rodríguez Portillo, J. Mariano

Estudio sobre el efecto del suplemento dietético con Magnesio sobre el grado de calcificación vascular y la densidad ósea en pacientes con enfermedad renal crónica grado 3b-4.
PI: Dr Rodríguez Portillo, J. Mariano

Members

Dr. Mariano Rodríguez Portillo

Principal Investigator

Team

Juan Rafael Muñoz Castañeda Escolástico Aguilera Tejera Antonio Luis Canalejo Raya Ignacio López Villalba Carmen María Pineda Martos Ana Isabel Raya Bermúdez María Encarnación Rodríguez Ortiz Cristian Rodelo Haad Juan Miguel Díaz Tocados Rodrigo López Baltanás María Victoria Pendón Ruiz de Mier Rafael Ríos Varo Noemi Vergara Segura Sandra García Valdivia Alicia Andújar Gil Cristina Membrives González Erena Ruiz Mora