Our Nephrology Cell Damage in Chronic Inflammation research group is a consolidated group of IMIBIC, bringing together both basic and clinical researchers in various scientific disciplines, including medicine, biology and nursing staff.
Our research group is focused on different aspects of uremia, hemodialysis, chronic inflammation and endothelial dysfunction. Our primary area of research is chronic kidney disease (CKD). We study CD14+CD16+ and endothelial cell interaction mediated induction of vascular calcification in patients with chronic kidney disease. We investigate the effect of the endothelial cell and production of microparticles as mediators of this process. We have also performed experimental models of cell culture to study microparticles, CD14 +CD16+ and endothelial cells by flow cytometry and proteomics (mass spectrometry) to analyze the role of these biological biomarkers on microinflammation and the mechanisms involved in vascular calcification on chronic kidney disease.
The main aim of our research is to study the mechanisms of cell damage and repair conditioning in the response to stress caused by chronic inflammation. The working model focuses on immunocompetent cells and vascular wall cells. In addition, we analyze the mechanisms regulating the stress response in circulating progenitor cells in peripheral blood.
Results derived from our research may lead to determine the benefits of different dialysis or pharmacological treatments (chelators, calcimimetic, and vitamin D) on morbidity and mortality of CKD2-4 CKD5 and CKD5D patients. Support tools at diagnosis and possible therapeutic targets will be identified.
In the last three year, our group has published manuscripts that are contributing to the understanding of Cell Damage in Chronic Inflammation and endothelial dysfunction on chronic kidney disease. We are also evaluated new biological biomarkers and the effect of different uremic toxins on the pathogenesis and development of vascular calcification and cardiovascular risk.
Our group is collaborating with the Spanish Renal Research Network (REDinREN). Other collaborations include research projects with companies of pharmaceutical/dialysis industry (Fresenius Medical Care, Vifor and Medtronic).
Research Lines
The latest technological advances in the treatment of chronic kidney disease have helped minimize the inflammation associated with the disease and improve our patients’ survival rates and quality of life. However, in these patients a microinflammatory state persists accompanied by a high percentage of activated cells that are capable of producing a sustained inflammatory response and can produce pathological complications when combined with other low-intensity stimuli. Our team assesses the effectiveness of pharmacological therapies, hemodialysis and kidney transplantation in improving this chronic microinflammatory state associated with kidney disease.
Mechanisms of cell damage and repair conditions the response to stress caused by chronic inflammation. The working model focuses on immunocompetent cells and vascular wall cells. In addition, we analyze the mechanisms regulating the stress response in circulating progenitor cells in peripheral blood.
Our aim is to determinate the role of pro-inflammatory monocytes in the induction of endothelial damage and vascular calcification (VCa) in patients with chronic kidney disease. The role of the endothelial cell and production of microparticles (MP) as mediators of this process will be characterized. In experimental models of cell culture, MP of pro-inflammatory monocytes (mMP) and endothelial cells (eMP) will be characterized by flow cytometry and proteomics (mass spectrometry). MicroRNA content to MP will be analyzed by qrtPCR. The effect of these MP on CaV smooth muscle cells will be analyzed by quantification of calcium and alkaline phosphatase. It will be also considered if the uremic serum stimulus modifies this activity.
A prospective study in patients from the Nephrology Unit of Reina Sofia University Hospital (Córdoba, Spain) will be performed. It will be analyzed if there is a relationship between the CaV, determined by a score of CaV developed by our group, and the number CD14 + CD16 +, MPM, MPE (Flow Cytometry) or microRNA profile (qRT-PCR) expressed in these MP or plasma of CKD patients.
In experimental models of cell culture, we evaluate the interactions between mononuclear and endothelial cells. Additionally, we are comparing two dialysis techniques (on-line HDF and high-flux hemodialysis) in a prospective randomized study in incident and prevalent hemodialysis patients. Preliminary results from in vitro studies show that uremic factors, indoxyl sulfate and p-Cresol, increase the adhesion and migration capacity of mononuclear cells, THP1. In addition, in vivo studies indicate that the dialysis procedure increases the expression of cell activation and adhesion markers. Uremic toxins bound--proteins could determine an increase in vascular disease associated with uremia.
Chronic kidney disease is currently a major public health around the world. Although hemodialysis increases survival of patients with end-stage renal disease, kidney transplantation remains the only potentially curative treatment. However, transplantation as a therapeutic option is limited by availability of suitable donor organs. This situation highlights the urgent need to find new and potentially inexhaustible sources of transplantable organs. Perfusion decellularization of whole organs is a novel approach to organ engineering and regeneration. In the present research, we use a continuous perfusion decellularization protocol to eliminate cellular componet of kidney and evaluate residual scaffold components after decellularization process by proteomics analysis. Our proteomic data shows that this protocol results in incomplete removal of cellular proteins. However, unlike other authors, we assume that proteins retained within decellularized kidney scaffold could be the basis for specific homing and celular differentation in the recellularization process.
Networks
REDinREN - Spanish Renal Research Network
Optimising Results in Dialysis - ORD group
Keywords
- Cell activation
- chronic renal failure
- microinflammation
- cell therapy
- hemodialysis
- renal transplantation
- inflammation
- cellular stress
- genomic damage
- endothelium
Additional Information
Highlighted recent publications:
Espinosa M, Ortega R, Sánchez M, Segarra A, Salcedo MT, González F, Camacho R, Valdivia MA, Cabrera R, López K, Pinedo F, Gutierrez E, Valera A, Leon M, Cobo MA, Rodriguez R, Ballarín J, Arce Y, García B, Muñoz MD, Praga M; Spanish Group for Study of Glomerular Diseases (GLOSEN). Association of C4d deposition with clinical outcomes in IgA nephropathy. Clin J Am SocNephrol. 2014. 9 (5). 897-904. PMID: 24578331
IF: 5,25.
Q: 1 D: 1
Buendia-Bello P; Carracedo J; Soriano S; Madueño JA; Ortiz, A; Martin-Malo A; Aljama P, Ramirez Rl. Klotho Prevents NFkB Translocation and Protects Endothelial Cell From Senescence Induced by Uremia. J Gerontol A Biol Sci Med Sci. 2015 Oct;70(10):1198-209. PMID: 25246106
IF: 5,416
Q: 1 D: 1
Buendia-Bello, P; Montes De Oca, Addy R; Madueño JA; Merino A; Martin-Malo A; Aljama P; Ramirez, R; Rodriguez M; Carracedo J. Endothelial microparticles mediate inflammation-induced vascular calcification. FASEB J. 2015 Jan;29(1):173-81. PMID: 25342130
IF: 5,704
Q: 1 D: 1
Cantisán S, Rodelo-Haad C, Páez-Vega A, Nieto A, Vaquero JM, Poyato A, Montejo M, Fariñas MC, Rivero A, Solana R, Martín-Malo A, Torre-Cisneros J. Factors related to the development of CMV-specific CD8+ T cell response in CMV-seropositive solid organ transplant candidates. Am J Transplant. 2015 Mar;15(3):715-22. PMID: 25648131
IF: 5,683
Q: 1 D: 1
Rabasco C, Cavero T, Román E, Rojas-Rivera J, Olea T, Espinosa M, Cabello V, Fernández-Juarez G, González F, Ávila A, Baltar JM, Díaz M,Alegre R, Elías S, Antón M, Frutos MA, Pobes A, Blasco M, Martín F, Bernis C, Macías M, Barroso S, de Lorenzo A, Ariceta G, López-Mendoza M, Rivas B, López-Revuelta K, Campistol JM, Mendizábal S, de Córdoba SR, Praga M. Effectiveness of mycophenolate mofetil in C3 glomerulonephritis. Kidney Int. 2015. 88(5): 1153-1160. PMID: 26221755
IF: 8,52
Q: 1 D: 1
Fernández-Ruiz M, Corrales I, Arias M, Campistol JM, Giménez E, Crespo J, López-Oliva MO, BeneytoI,Martín-Moreno PL, Llamas-Fuente F, Gutiérrez A, García-Álvarez T, Guerra-Rodríguez R, Calvo N,Fernández-Rodríguez A, Tabernero-Romo JM, Navarro MD, Ramos-Verde A, Aguado JM, Navarro D;OPERA StudyGroup. Association between individual and combined SNPs in genes related toinnate immunity and incidence of CMV infection in seropositive kidneytransplant recipients. Am J Transplant. 2015 May;15(5):1323-35. PMID: 25777542
IF: 5,683
Q: 1 D: 1
Maduell F, Ramos R, Varas J, Martin-Malo A, Molina M, Pérez-Garcia R, Marcelli D, Moreso F, Aljama P, Merello JI. Hemodialysis patients receiving a greater Kt dose than recommended have reduced mortality and hospitalization risk. Kidney Int. 2016 Dec;90(6):1332-134. PMID: 27780586
IF: 7,683
Q: 1 D: 1
Fakhouri F, Hourmant M, Campistol JM, Cataland SR, Espinosa M, Gaber AO, Menne J, Minetti EE, Provôt F, Rondeau E, RuggenentiP,Weekers LE, Ogawa M, Bedrosian CL, Legendre CM. Terminal Complement Inhibitor Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome: A Single-Arm, Open-Label Trial. Am J Kidney Dis. 2016 Jul;68(1):84-93. PMID: 27012908
IF: 7,623
Q: 1
Molina J, Navas A, Agüera ML, Rodelo-Haad C, Alonso C, Rodríguez-Benot A, Aljama P, Solana R. Impact of Preformed Donor-Specific Antihuman leukocyte Antigen Antibody C1q-Binding Abilityon Kidney Allograft Outcome. Front Immunol. 2017 Oct 31;8:1310. PMID: 29163462
IF: 6,429
Q: 1 D: 2
Tortajada A, Gutiérrez E, Goicoechea de Jorge E, Anter J, Segarra A, Espinosa M, Blasco M, Roman E, Marco H, Quintana LF, Gutiérrez J, Pinto S, Lopez-Trascasa M, Praga M, Rodriguez de Córdoba S. Elevated factor H-related protein 1 and factor H pathogenic variants decrease complement regulation in IgA nephropathy. Kidney Int. 2017 Oct;92(4):953-963. PMID:28637589
IF: 8,395
Q: 1 D: 1
Huerta A, Arjona E, Portoles J, Lopez-Sanchez P, Rabasco C, Espinosa M, Cavero T, Blasco M, Cao M, Manrique J, Cabello-Chavez V, Suñer M, Heras M, Fulladosa X, Belmar L, Sempere A, Peralta C, Castillo L, Arnau A, Praga M, Rodriguez de Cordoba S17. A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome. Kidney Int. 2018 Feb;93(2):450-459. PMID: 28911789
IF: 8,395
Q: 1 D: 1
Ayasreh N, Bullich G, Miquel R, Furlano M, Ruiz P, Lorente L, Valero O, García-González MA, Arhda N, Garin I, Martínez V, Pérez-Gómez V, Fulladosa X, Arroyo D, Martínez-Vea A, Espinosa M, Ballarín J, Ars E, Torra R. Autosomal Dominant Tubulointerstitial Kidney Disease: Clinical Presentation of Patients With ADTKD-UMOD and ADTKD-MUC1. Am J Kidney Dis. 2018 May 18. pii: S0272-6386(18)30606-1. PMID:29784615 IF: 7,129
Q: 1 D: 1
Díaz-Tocados JM, Rodríguez-Ortiz ME, Almadén Y, Pineda C, Martínez-Moreno JM, Herencia C, Vergara N, Pendón-Ruiz de Mier MV, Santamaría R, Rodelo-Haad C, Casado-Díaz A, Lorenzo V, Carvalho C, Frazão JM, Felsenfeld AJ, Richards WG1, Aguilera-Tejero E, Rodríguez M, López I, Muñoz-Castañeda JR. Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration. Kidney Int. 2019 Mar 12. pii: S0085-2538(19)30043-2. PMID 30878213
IF: 8,52
Q: 1 D: 1
Fernández-Ruiz M, Giménez E, Vinuesa V, Ruiz-Merlo T, Parra P, Amat P, Montejo M, Paez-Vega A, Cantisán S, Torre-Cisneros J, Fortún J, Andrés A, San Juan R, López-Medrano F, Navarro D, Aguado JM; Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI). Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment. Clin Microbiol Infect. 2019 Mar;25(3):381. PMID 29803844
IF 5,394
Q: 1 D: 1
Varas J, Pérez-Sáez MJ, Ramos R, Merello JI, de Francisco ALM, Luño J, Praga M, Aljama P, Pascual J; Optimizing Results in Dialysis (ORD) group. Returning to haemodialysis after kidney allograft failure: a survival study with propensity score matching. Nephrol Dial Transplant. 2019 Apr 1;34(4):667-672. PMID 30053152
IF: 4,6
Q: 1 D: 2
Patents:
Método de obtención de datos útiles para el diagnóstico de la calcifiacción vascular. Carracedo J, Soriano S, Rodriguez-Portillo JM, Ramirez-Chamond R, Aljama P.
Recent Research Projects:
Actividad inflamatoria mediada por la interacción de CD14+CD16+ con el endotelio; Un proceso implicado en la inducción de calcificación vascular en pacientes con enfermedad renal crónica. (PI15/01785. FONDO DE INVESTIGACIÓN SANITARIA (FIS). 01/01/2016 - 31/12/2018)
PI: Aljama-Garcia, Pedro
Red de Investigación Renal (RD12/0021/0011 Subdirección de Redes Temáticas de investigación cooperativa. Fondo de Investigación Sanitaria (FIS) del Instituto de Salud Carlos III. 01/01/2014 - 31/12/2017)
PI: Aljama-Garcia, Pedro
Inteligencia Artificial: Una Nueva Alternativa para Analizar las Asociaciones Entre las Concentraciones de Calcio, Fosforo y Pth en Los Pacientes en Hemodiálisis y Predecir el Riesgo Cardio-vascular. (PI-0311-2014. Proyectos de Investigación en Biomédica y en Ciencias de la Salud en Andalucía. 03/08/2015 – 03/08/2017)
PI: Martín Malo, Alejandro
Mecanismos moleculares implicados en los procesos de adhesión y migración celular: Efecto del tratamiento de enfermedad renal crónica sobre la disfunción endotelial. (PI 17/01785. FONDO DE INVESTIGACIÓN SANITARIA (FIS). 01/01/2018 – 31/12/2020)
PI: Martín Malo, Alejandro
