Bone Metabolism, Vascular Metabolism and Chronic Inflammatory Diseases

The Bone Metabolism, Vascular Metabolism and Chronic Inflammatory Diseases research group is a multidisciplinary team which is committed to the translation of results and performs its research in the clinical, epidemiological and experimental fields. Its work falls within the “Demographic Ageing and Quality of Life” section of the RIS3 Smart Specialisation Strategy for Asturias. The research group is currently composed of the following members:

The H-indices (Web of Science database – FECYT) of the group’s “senior” members are as follows: Jorge Cannata-Andía 50, Adriana Dusso 37, Manuel Naves 27, José Luis Fernández Martín 20, Natalia Carrillo López 10, Emilio Sánchez Álvarez 9, Minerva Rodríguez García, Carmen Rodríguez Suárez and Cristina Alonso Montes 8 (June 2018).

The group has published over 650 articles (90% in English), edited two books and produced more than 100 book chapters, its English publications having an average impact factor of 5.39. The group’s scientific output has maintained a consistent level of quality over the last decade, with 60-70% of its publications appearing in Q1 journals, and 15-25% of these within the top decile. It has also received over 50 awards, four of which were related to scientific careers and training.

The group leader and principal investigator was Research Coordinator and Chair of the Research Commission for the Hospital Universitario Central de Asturias (HUCA) between 1993 and 2007: the period in which most of HUCA’s research infrastructure was consolidated. He has been Research Institute Accreditation Auditor for Instituto de Salud Carlos III since 2010, and is an honorary member of eight scientific societies (six of which are international).

The research group was consolidated in 1987, initially focusing exclusively on the bone and mineral metabolism disorders that occur as a result of decreased kidney function and ageing, before gradually incorporating vascular and valvular calcification into its lines of research. The research group formed part of the Bone and Mineral Metabolism Department of the Hospital General de Asturias, which became part of the Hospital Universitario Central de Asturias after the hospitals were merged. The group was part of IRSIN (Reina Sofía Research Institute) at the Fundación Renal Íñigo Álvarez de Toledo (Íñigo Álvarez de Toledo Kidney Foundation) from the date IRSIN was created in 1994 until 2016, when it was dissolved. It has also been a member of REDinREN (the cooperative Renal Research Network) since 2008 (ISCIII-Retic-RD06/0016/06, RD12/0021/1023 and RD16/0009/0017) and has been an Universidad de Oviedo approved research group since 2013.

The group which developed out of the initial formation consolidated in 1987 has designed, led and conducted 12 clinical-epidemiological research projects, 32 clinical-experimental projects and 28 basic-experimental projects. Forty-four of these projects were competitively funded (by state or international RDI organisations) and 28 were non-competitively funded (through contracts and/or research agreements).

Of those allocated non-competitive funding, it is worth highlighting two large-scale, international epidemiological studies designed, led and conducted by the Bone and Mineral Metabolism research group: the CORES (Controlling Renal Osteodystrophy in South America) project, with 16173 patients in six South American countries, completed in 2012 (Argentina, Brazil, Chile, Colombia, Mexico and Venezuela); and the COSMOS (Current Management Of Secondary Hyperparathyroidism: a Multicentre Observational Study) project, with 6797 patients at 227 sites in 20 European countries (Austria, Belgium, Croatia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Poland, Portugal, Romania, Slovenia, Spain, Sweden, Switzerland and the United Kingdom).

In addition to the CORES, COSMOS and other research projects mentioned above, the Bone and Mineral Metabolism group has completed 11 international cooperation interventions, supported by partnerships with the Spanish Ministry of Education – British Council (5), the Agencia Española de Cooperación Internacional para el Desarrollo (Spanish Agency for International Development Cooperation ; 4), the University of Antwerp (Belgium) and the Universidade de São Paulo (Brazil).

• Epidemiology, diagnosis and treatment of mineral and bone metabolism disorders in stage 5 chronic kidney disease (CKD-MBD). COSMOS Study.
• Molecular mechanisms involved in vascular calcification, mineralisation, ageing, immunological disorders and chronic kidney disease (CKD).
• Synergy between vitamin D and β-glucans in mitigating vascular and immunological ageing of the renal vascular and cardiovascular tissue.
• Identification of early biomarkers for endothelial damage and cardiovascular risk. Determination of mechanisms of action.
• The usefulness of genetic and molecular markers in early diagnosis of a chronic decrease in kidney function.
• Molecular mechanisms of valvular calcification in severe aortic stenosis and restenosis in stents.
• Studying microRNAs that regulate the RANK/RANKL/OPG pathway as predictors of vascular mineralisation (calcification) and bone demineralisation.
• The role of exosomes in mineral metabolism disorders and inflammation.

Journal Publications

The group has published a total of 88 articles in the last five years: 74 in English and 14 in Spanish. Of the English-language publications, 39 appear in Q1 journals and nine in Q2 publications, with a cumulative impact factor of 354.1. We have selected 25 of these publications which represent the results of the group’s lines of research, and some of its collaborations:

• Alonso-Montes C, Martín M, Martínez-Arias L, Coto E, Naves-Díaz M, Morís C, Cannata-Andía JB, Rodríguez I. Variants in cardiac GATA genes associated with bicuspid aortic valve. Eur J clin Invest., 2018 Sep 19:e13027. doi: 10.1111/eci.13027. I.F.: 3.086 Quartile: Q1
• Rodríguez-Carrio J, Martinez-Zapico A, Cabezas-Rodríguez I, Benavente L, Pérez-Álvarez AI, López P, Cannata-Andía JB, Naves Díaz M, Suárez A. Clinical and subclinical cardiovascular disease in female SLE patients: interplay between body mass index and bone mineral density. Nutrition, Metabolism and Cardiovascular Diseases, 2018 (in press). I.F.: 3.318 Quartile: Q2
• Fernández-Martín JL, Dusso A, Martínez-Camblor P, Dionisi MP, Floege J,Ketteler M, London G, Locatelli F, Górriz JL, Rutkowski B, Bos WJ, Tielemans C, Martin PY, Wüthrich RP, Pavlovic D, Benedik M, Rodríguez-Puyol D, Carrero JJ, Zoccali C, Cannata-Andía JB. Serum phosphate optimal timing and range associated with patients survival in haemodialysis: the COSMOS study. Nephrol Dial Transplant. 2018 May 7. doi: 10.1093/ndt/gfy093. IF.: 4.470 Quartile: Q1
• Fusaro M, Cannata-Andía JB, Nickolas TL, Plebani M, Mereu MC, Aghi A, Gallieni M. Clinical relevance and future perspective of fractures in patients withchronic kidney disease. Kidney Int. 2018 May;93(5):1248. doi:10.1016/j.kint.2018.02.012. IF.: 8.395 Quartile: Q1(D1)
• Dusso A, Colombo MI, Shanahan CM. Not all vascular smooth muscle cell exosomes calcify equally in chronic kidney disease. Kidney Int 93:298-301, 2018. IF.: 8.395 Quartile: Q1(D1)
• Panizo S, Carrillo-López N, Naves-Díaz M, Solache-Berrocal G, Martínez-Arias L, Rodrigues-Díez RR, Fernández-Vázquez A, Martínez-Salgado C, Ruiz-Ortega M, Dusso A, Cannata-Andía JB, Rodríguez I. Regulation of miR-29b and miR-30c by vitamin D receptor activators contributes to attenuate uraemia-induced cardiacfibrosis. Nephrol Dial Transplant. 2017 Nov 1;32(11):1831-1840. doi:10.1093/ndt/gfx060. IF.: 4.470 Quartile: Q1
• Alonso-Montes C, Rodríguez-Reguero J, Martín M, Gómez J, Coto E, Naves-Díaz M, Morís C, Cannata-Andía JB, Rodríguez I. Rare genetic variants in GATAtranscription factors in patients with hypertrophic cardiomyopathy. J InvestigMed. 2017 Jun;65(5):926-934. doi: 10.1136/jim-2016-000364. IF.: 1.943 Quartile: Q2
• Moyses RMA, Dusso A. Is osteocyte Klotho bad for bone health? Kidney Int 92:540-543, 2017. IF.: 8.395 Quartile: Q1(D1)
• Evenepoel P, D’Haese P, Bacchetta J, Cannata-Andia J, Ferreira A, Haarhaus M, Mazzaferro S, Lafage Proust MH, Salam S, Spasovski G, Cozzolino M, CKD-MBD E-EWGo. Bone biopsy practice patterns across Europe: the European renal osteodystrophy initiative-a position paper. Nephrol Dial Transplant 32:1608-1613, 2017. IF.: 4.470 Quartile: Q1
• Armbrecht G, Felsenberg D, Ganswindt M, Lunt M, Kaptoge SK, Abendroth K, Aroso Dias A, Bhalla AK, Cannata Andia J, Dequeker J, Eastell R, Hoszowski K, Lyritis G, Masaryk P, van Meurs J, Miazgowski T, Nuti R, Poor G, Redlund-Johnell I, Reid DM, Schatz H, Todd CJ, Woolf AD, Rivadeneira F, Javaid MK, Cooper C, Silman AJ, O’Neill TW, Reeve J, European Vertebral Osteoporosis S, European Prospective Osteoporosis Study G. Degenerative inter-vertebral disc disease osteochondrosis intervertebralis in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over. Rheumatology (Oxford) 56:1189-1199, 2017. IF.: 4.818 Quartile: Q1
• N. Carrillo-López, S. Panizo, C. Alonso-Montes, P. Román-García, I. Rodríguez García, C. Martinez-Salgado, A. Dusso, M. Naves Díaz, J. B. Cannata-Andía. Direct inhibition of osteoblastic Wnt pathway by fibroblast growth factor 23 contributes to bone loss in chronic kidney disease. Kidney Int. 2016 Jul;90(1):77-89. IF.: 8.395 Quartile: Q1(D1)
• J. B. Cannata-Andia, K. J. Martin. The challenge of controlling phosphorus in chronic kidney disease. Nephrol Dial Transplant. 2016 Apr;31(4):541-7. IF.: 4.470 Quartile: Q1
• I. Quiros-Gonzalez, P. Roman-Garcia, C. Alonso-Montes, S. Barrio-Vazquez, N. Carrillo-Lopez, M. Naves-Diaz, M. I. Mora, F. J. Corrales, F. J. Lopez-Hernandez, M. P. Ruiz-Torres, J. B. Cannata-Andia, J. L. Fernandez-Martin. Lamin A is involved in the development of vascular calcification induced by chronic kidney failure and phosphorus load. Bone 84: 160-8; 2016. IF.:4.140 Quartile: Q1
• J. L. Fernandez-Martin, P. Martinez-Camblor, M. P. Dionisi, J. Floege, M. Ketteler, G. London, F. Locatelli, J. L. Gorriz, B. Rutkowski, A. Ferreira, W. J. Bos, A. Covic, M. Rodriguez-Garcia, J. E. Sanchez, D. Rodriguez-Puyol, J. B. Cannata-Andia. Improvement of mineral and bone metabolism markers is associated with better survival in haemodialysis patients: the COSMOS study. Nephrol Dial Transplant 30: 1542-51; 2015. IF.: 4.470 Quartile: Q1
• S. Panizo, M. Naves-Diaz, N. Carrillo-Lopez, L. Martinez-Arias, J. L. Fernandez-Martin, M. P. Ruiz-Torres, J. B. Cannata-Andia, I. Rodriguez. MicroRNAs 29b, 133b, and 211 Regulate Vascular Smooth Muscle Calcification Mediated by High Phosphorus. J Am SocNephrol 27: 824-34; 2016. IF.:8.966 Quartile: Q1 (D1)
• D. Tuñón-Le Poultel, J. B. Cannata-Andia, P. Roman-Garcia, J. B. Diaz-Lopez, E. Coto, C. Gomez, M. Naves-Diaz, I. Rodriguez. Association of matrix Gla protein gene functional polymorphisms with loss of bone mineral density and progression of aortic calcification. OsteoporosInt 25: 1237-1246; 2014. IF.: 3.591 Quartile: Q2
• P. Roman-Garcia, I. Quiros-Gonzalez, L. Mottram, L. Lieben, K. Sharan, A. Wangwiwatsin, J. Tubio, K. Lewis, D. Wilkinson, B. Santhanam, N. Sarper, S. Clare, G. S. Vassiliou, V. R. Velagapudi, G. Dougan, V. K. Yadav. Vitamin B(1)(2)-dependent taurine synthesis regulates growth and bone mass. J ClinInvest 124: 2988-3002; 2014. IF.: 12.784 Quartile: Q1 (D1)
• A. Betriu, M. Martinez-Alonso, M. V. Arcidiacono, J. Cannata-Andia, J. Pascual, J. M. Valdivielso, E. Fernandez. Prevalence of subclinical atheromatosis and associated risk factors in chronic kidney disease: the NEFRONA study. Nephrol Dial Transplant 29: 1415-22; 2014. IF.: 4.470 Quartile: Q1
• J. M. Quesada-Gomez, M. Diaz-Curiel, M. Sosa-Henriquez, J. Malouf-Sierra, X. Nogues-Solan, C. Gomez-Alonso, L. Rodriguez-Manas, J. L. Neyro-Bilbao, X. Cortes, J. Delgadillo. Low calcium intake and inadequate vitamin D status in postmenopausal osteoporotic women. J Steroid BiochemMolBiol 136: 175-7; 2013. IF.:4.561 Quartile: Q1
• S. Panizo, S. Barrio-Vazquez, M. Naves-Diaz, N. Carrillo-Lopez, I. Rodriguez, A. Fernandez-Vazquez, J. M. Valdivielso, R. Thadhani, J. B. Cannata-Andia. Vitamin D receptor activation, left ventricular hypertrophy and myocardial fibrosis. Nephrol Dial Transplant 28: 2735-44; 2013. IF.: 4.470 Quartile: Q1
• J. L. Fernandez-Martin, J. J. Carrero, M. Benedik, W. J. Bos, A. Covic, A. Ferreira, J.Floege, D. Goldsmith, J. L. Gorriz, M. Ketteler, R. Kramar, F. Locatelli, G. London, P. Y. Martin, D. Memmos, J. Nagy, M. Naves-Diaz, D. Pavlovic, M. Rodriguez-Garcia, B. Rutkowski, V. Teplan, C. Tielemans, D. Verbeelen, R. P. Wuthrich, P. Martinez-Camblor, I. Cabezas-Rodriguez, J. E. Sanchez-Alvarez, J. B. Cannata-Andia. COSMOS: the dialysis scenario of CKD-MBD in Europe. Nephrol Dial Transplant 28: 1922-35; 2013. IF.:4.470 Quartile: Q1
• J. B. Cannata-Andia, J. L. Fernandez-Martin, F. Locatelli, G. London, J. L. Gorriz, J. Floege, M. Ketteler, A. Ferreira, A. Covic, B. Rutkowski, D. Memmos, W. J. Bos, V. Teplan, J. Nagy, C. Tielemans, D. Verbeelen, D. Goldsmith, R. Kramar, P. Y. Martin, R. P. Wuthrich, D. Pavlovic, M. Benedik, J. E. Sanchez, P. Martinez-Camblor, M. Naves-Diaz, J. J. Carrero, C. Zoccali. Use of phosphate-binding agents is associated with a lower risk of mortality. Kidney Int 84: 998-1008; 2013. IF.: 8.395 Quartile: Q1(D1)
• I. Cabezas-Rodriguez, J. J. Carrero, C. Zoccali, A. R. Qureshi, M. Ketteler, J. Floege, G. London, F. Locatelli, J. L. Gorriz, B. Rutkowski, D. Memmos, A. Ferreira, A. Covic, V. Teplan, W. J. Bos, R. Kramar, D. Pavlovic, D. Goldsmith, J. Nagy, M. Benedik, D. Verbeelen, C. Tielemans, R. P. Wuthrich, P. Y. Martin, C. Martinez-Salgado, J. L. Fernandez-Martin, J. B. Cannata-Andia. Influence of body mass index on the association of weight changes with mortality in hemodialysis patients. Clin J Am SocNephrol 8: 1725-1733; 2013. IF.: 4.780 Quartile: Q1

Book Chapters

Six in the last five years (five in English and one in Spanish):

• Vitamin D and renal disease. Dusso A, Cannata-Andía JB. In Vitamin D 4th Edition, edited by David Feldman JWP, Roger Bouillon,Edward Giovannucci,David Goltzman,Martin Hewison 2017, pp 445-469.
• Dietary phosphorus regulation of vitamin D metabolism in the kidney. Dusso A, Arcidiacono M, Carrillo-López N, Cannata-Andía JB. In Dietary Phosphorus – Health, Nutrition and Regulatory Aspects ( Chapter 11), edited by Calvo JUaMS, CRC Press is an imprint of Taylor & Francis Group, an Informa business, 2016.
• Clinical and pre-clinical evidence of the skeletal/vascular adverse health effects of high dietary phospohorus. Cannata-Andía JB, Román-García P, Carrillo-López N, Dusso A. In Dietary Phosphorus – Health, Nutrition and Regulatory Aspects ( Chapter 3), edited by Calvo JUaMS, CRC Press is an imprint of Taylor & Francis Group, an Informa business, 2016.
• Molecular Biology of Vitamin D: Genomic and Nongenomic Actions of Vitamin D in Chronic Kidney Disease. Dusso A. In Vitamin D in Chronic Kidney Disease, edited by Ureña Torres P. CM, Vervloet M. , Springer, Cham, 2016, pp 51-74.
• Mineral and bone disorders in CKD. Cannata-Andía JB, N. C-L-, Rodríguez-García M, Torregrosa, V. In Management of Chronic Kidney Disease, edited by Arici, Springer, 2014, pp 223-239.
• Metabolismo Calcio-Fósforo y sus alteraciones. Cannata-Andía JB, Rodríguez García M. In Nefrología Clínica, edited by Hernando L, Arias M, Aljama P, Egido J, Lamas S, Praga M, Serón D, Editorial Médica Panamericana, 2013, pp 147-160.

Collaborations with external groups

• The Bone Metabolism group leads, sponsors and manages the design and realisation of the European COSMOS Study (Current Management Of Secondary Hyperparathyroidism: a Multicentre Observational Study). This is a large-scale study, involving 20 European countries and 6797 patients, with a follow-up period of three years.
• Collaboration with the University of Amsterdam, Cardiovascular Division, VU Medical Center. Title of collaboration: The central role of the cardiomyocyte exosomes resulting from cardiac hypertrophy in chronic kidney disease (Drs Marc Vervloet and Diederik Kuster; September – December 2018).
• Member of the Executive Committee of the EUROD (European Renal Osteodystrophy): a project with UC Louvain and ERA-EDTA (European Renal Association – European Dialysis and Transplant Association) recording vertebral fractures and bone biopsies in Europe in chronic kidney disease patients.
• Collaboration with the Cardiovascular Division, King’s College London (UK), Catherine Shanahan, (Vascular calcification).
• Collaboration with the Department of Morphology, Surgery and Experimental Medicine and the LTTA Centre, Università degli Studi di Ferrara, Italy (histological characterisation of parathyroid disorders in the progression of kidney damage using a transgenic mouse that does not develop secondary hyperparathyroidism).
• Collaboration with the Kidney Division, Karolinska Institutet, Stockholm, Sweden (cardiovascular disorders in peritoneal dialysis, vascular stiffness, calcification).
• Collaboration on the NEFRONA Project genetic studies: “Observational, prospective and multicentre study to establish an atherosclerosis assessment model and its value for predicting cardiovascular events in chronic kidney disease patients in Spain” (Hospital Universitari Arnau de Vilanova, Lleida).
• Collaboration with the Fundación Jiménez Díaz of Madrid (functional study of the gremlin protein).
• Collaboration with the Universidad de Alcalá de Henares (studies of oxidative stress markers in vascular calcification processes).
• Collaboration with the Universidad de Salamanca (a study of kidney fibrosis in an animal model with chronic kidney failure and parathyroidectomy).

Collaborations with Biotechnology Companies and Private Institutions (Spin-off)

• Collaboration agreement with the ENTRECHEM SL biotechnology company (analysis of the effects of mithramycin analogues in an in vitro vascular calcification model).
• Collaboration with HEALTHSENS (member of the Scientific Advisory Board).

• Postdoctoral employment opportunity connected to the GRUPIN-18-152 grant (19/12/2018)
• Employment opportunity for a Master’s-level graduate, connected to REDinREN RD16-0009-0017 (19/12/2018)