Izquierdo M.C.,Autonomous University of Madrid |
Sanz A.B.,Servicio de Nefrologia |
Mezzano S.,Austral University of Chile |
Blanco J.,Hospital Clinico San Carlos |
And 7 more authors.
Kidney International | Year: 2012
TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a TNF superfamily cytokine that activates the fibroblast growth factor-inducible 14 (Fn14) receptor. Transcriptional analysis of experimental kidney tubulointerstitial inflammation showed a correlation between an upregulation of the mRNA for the transmembrane chemokine CXCL16, a T-cell chemoattractant, and Fn14 activation. Exogenous TWEAK increased mouse kidney CXCL16 expression and T-lymphocyte infiltration in vivo, processes inhibited by the NF-B inhibitor parthenolide. Tubular cell CXCL16 was increased in a nephrotoxic tubulointerstitial inflammation model and neutralizing anti-TWEAK antibodies decreased this CXCL16 expression and lymphocyte infiltration. In human kidney biopsies with tubulointerstitial inflammation, tubular cell CXCL16 and Fn14 expressions were associated with inflammatory infiltrates. TWEAK upregulated CXCL16 mRNA expression in cultured renal tubular cells in an NF-B-dependent manner and increased soluble and cellular CXCL16 protein. CXCL16 modestly promoted the expression of cytokines in tubular cells expressing its receptor (CXCR6) and appeared to synergize with TWEAK to promote an inflammatory response; however, it did not modulate tubular cell proliferation or survival. Thus, TWEAK upregulates the expression of the chemokine CXCL16 in tubular epithelium and this may contribute to kidney tubulointerstitial inflammation. © 2012 International Society of Nephrology.
Moreno J.A.,Autonomous University of Madrid |
Izquierdo M.C.,Autonomous University of Madrid |
Sanchez-Nino M.D.,Autonomous University of Madrid |
Suarez-Alvarez B.,Hospital Universitario Central Of Asturias |
And 9 more authors.
Journal of the American Society of Nephrology | Year: 2011
Proinflammatory cytokines contribute to renal injury, but the downstream effectors within kidney cells are not well understood. One candidate effector is Klotho, a protein expressed by renal cells that has antiaging properties; Klotho-deficient mice have an accelerated aging-like phenotype, including vascular injury and renal injury. Whether proinflammatory cytokines, such as TNF and TNF-like weak inducer of apoptosis (TWEAK), modulate Klotho is unknown. In mice, exogenous administration of TWEAK decreased expression of Klotho in the kidney. In the setting of acute kidney injury induced by folic acid, the blockade or absence of TWEAK abrogated the injury-related decrease in renal and plasma Klotho levels. TWEAK, TNFα, and siRNA-mediated knockdown of IκBα all activated NFκB and reduced Klotho expression in the MCT tubular cell line. Furthermore, inhibition of NFκB with parthenolide prevented TWEAK- or TNFα-induced downregulation of Klotho. Inhibition of histone deacetylase reversed TWEAKinduced downregulation of Klotho, and chromatin immunoprecipitation showed that TWEAK promotes RelA binding to the Klotho promoter, inducing its deacetylation. In conclusion, inflammatory cytokines, such as TWEAK and TNFα, downregulate Klotho expression through an NFκB-dependent mechanism. These results may partially explain the relationship between inflammation and diseases characterized by accelerated aging of organs, including CKD. Copyright © 2011 by the American Society of Nephrology.
PubMed | Hospital Joan XXIII, Hospital Sant Pau, Hospital Mutua Of Terrassa, Autonomous University of Barcelona and 9 more.
Type: | Journal: Medicina intensiva | Year: 2016
The aim of the study is to ascertain the most relevant aspects of the current management of renal replacement therapy (RRT) in critically ill patients, and to analyze renal function recovery and mortality in patients undergoing RRT.A non-interventional three-month observational study was made in 2012, with a follow-up period of 90 days, in 21 centers in Catalonia (Spain). Demographic information, severity scores and clinical data were obtained, as well as RRT parameters.patients aged 16 years admitted to Intensive Care Units (ICUs) and subjected to RRT.A total of 261 critically ill patients were recruited, of which 35% had renal dysfunction prior to admission. The main reason for starting RRT was oliguria; the most widely used RRT modality was hemodiafiltration; and the median prescribed dose at baseline was 35mL/kg/h. The median time of RRT onset from ICU admission was one day. The mortality rate at 30 and 90 days was 46% and 54%, respectively, and was associated to greater severity scores and a later onset of RRT. At discharge, 85% of the survivors had recovered renal function.Current practice in RRT in Catalonia abides with the current clinical practice guidelines. Mortality related to RRT is associated to later onset of such therapy. The renal function recovery rate at hospital discharge was 85% among the patients subjected to RRT.
Montanez-Barragan A.,National Polytechnic Institute of Mexico |
Gomez-Barrera I.,National Polytechnic Institute of Mexico |
Sanchez-Nino M.D.,Servicio de Nefrologia |
Ucero A.C.,Autonomous University of Madrid |
And 2 more authors.
Journal of Nephrology | Year: 2014
Vascular calcification in chronic kidney disease (CKD) patients is associated to increased mortality. Osteoprotegerin (OPG) is a soluble tumor necrosis factor (TNF) superfamily receptor that inhibits the actions of the cytokines receptor activator of nuclear factor kappa-B ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL) by preventing their binding to signaling receptors in the cell membrane. OPG-deficient mice display vascular calcification while OPG prevented calcification of cultured vascular smooth muscle cells and protected kidney cells from TRAIL-induced death. OPG may be a biomarker in patients with kidney disease. Circulating OPG is increased in predialysis, dialysis and transplant CKD patients and may predict vascular calcification progression and patient survival. By contrast, circulating OPG is decreased in nephrotic syndrome. In addition, free and exosome-bound urinary OPG is increased in human kidney disease. Increased urinary OPG has been associated with lupus nephritis activity. Despite the association of high OPG levels with disease, experimental functional information available suggests that OPG might be protective in kidney disease and in vascular injury in the context of uremia. Thus, tissue injury results in increased OPG, while OPG may protect from tissue injury. Recombinant OPG was safe in phase I randomized controlled trials. Further research is needed to fully define the therapeutic and biomarker potential of OPG in patients with kidney disease. © 2014, Italian Society of Nephrology.
Sanchez-Nino M.D.,Servicio de Nefrologia |
Ortiz A.,Autonomous University of Madrid
Journal of Pathology | Year: 2012
Notch receptors and their canonical ligands are transmembrane proteins of the EGF-like family, expressed in the cell surface. Notch receptors are synthesized as single peptides and undergo three sequential proteolytic cleavage steps before rendering an active transcription factor, the Notch intracellular domain (NICD). Ligand binding facilitates release of NICD by γ-secretase. Evidence for the role of the Notch pathway in kidney injury comes from studies on activation of Notch by canonical ligands in cultured cells, on inhibition/targeting of γ-secretase in culture or in vivo, on genetic deletion of common Notch pathway proteins such as CSL, or descriptions of increased transcription of Notch target genes in kidney injury. Inhibitors of γ-secretase prevent fibrosis in experimental kidney injury. However, these drugs may modulate other signalling systems beyond Notch and are toxic in human trials. Information regarding the specific contribution of each receptor to kidney injury may help design better targeted therapeutic approaches. In this regard, overexpression of NICD1, NCID2, NICD3 or NICD4 elicits biological responses in cultured renal cells that include cell proliferation, apoptosis, and inflammatory and profibrotic responses, depending on the particular NICD. Furthermore, immunostaining for NICD1, NICD2, and NICD4 suggestive of receptor activation has been observed in glomerular and tubular cells in human and experimental kidney disease. Delayed conditional Notch1 or Notch2 inactivation facilitates cyst formation, and NICD1 overexpression in podocytes or tubular cells promotes glomerulosclerosis and interstitial fibrosis. Kidney injury is a feature of human Notch2 mutations and CADASIL patients with mutated Notch3 may display renal injury. Notch3-/- mice display increased sensitivity to angiotensin II-induced kidney injury but are less sensitive to tubular injury, inflammation, and fibrosis following unilateral ureteral obstruction. The recent availability of blocking antibodies specific for Notch1, Notch2, and Notch3 may help to elucidate the therapeutic potential of specific targeting of individual Notch receptors in kidney disease. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Gutierrez E.,Hospital Universitario 12 Of Octubre |
Moreno J.A.,Servicio de Nefrologia |
Praga M.,Complutense University of Madrid
Nefrologia | Year: 2014
The quantity of proteinuria continues to be the clinical parameter that is best related to the development of longterm renal failure in glomerular pathologies. This quantity is particularly important when we analyse the progression of patients with IgA nephropathy. As such, the natural progression of patients with IgA who clinically present with normal kidney function, microhaematuria and low proteinuria had not been analysed comprehensively until this Spanish multicentre study was developed, which analyses it herein. After studying 141 Caucasian patients with biopsied IgA nephropathy and a "benign" clinical profile and after they were classified histologically in accordance with the new Oxford classification, it could be concluded that the renal prognosis of these patients was excellent. This is the first study in the literature that demonstrates the usefulness of this new classification in patients who clinically have normal renal function and proteinuria of less than 0.5g/day. The latest advances in the genetics of this disease, as well as in the collaboration of complement pathways in its pathophysiology mean that these results cannot be extrapolated to all the populations studied. In addition, the analysis and follow-up of microhaematuria has regained importance as an independent prognosis factor for developing renal failure, although there are as yet no consistent studies in this regard. However, it is a subject that should be examined again by the nephrology community. © 2014 Revista Nefrología.
PubMed | Hospital Regional, Servicio de Nefrologia and Hospital Torrecardenas
Type: Journal Article | Journal: Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia | Year: 2016
Renal failure is one of the main causes of death in patients with Fabry disease (FD). Due to the low prevalence of FD, delayed diagnosis and misdiagnosis, often the correct diagnosis is made when organ damage is already present. Early recognition of the disease would allow the prevention of severe complications and the premature death of patients with FD.We present here the PrEFiNE project, which includes a wide spectrum of activities with the aim of improve knowledge and diagnosis of FD. The project is sponsored by Shire Iberia (http://shireiberica.com/)From January 2016 to the end of 2017 several activities will be carried out, starting with a survey to evaluate current FD knowledge among nephrologists; in addition some studies to assess prevalence of this disease will be performed. One study will include patients receiving dialysis, another study will cover kidney transplant patients, and a pilot study in chronic kidney disease in stage 3-5 predialysis. Also planned is a pharmacoeconomic study to focus on burden of FD. At the same time medical education activities will be conducted both on line and on site. Plan for dissemination will include medical publications and diffusion to media. PrEFiNE Project will finish with the publication of a compilation book on FD in Nephrology including all planned activities and proposing recommendations based on results and detected unmet needs. PrEfiNE Plan will be coordinated by severa scientific committees, one at national level and 10 other regionals comittees, tha will be responsible to ensure the maximum scientific quality of proposed activities. An advisory board will supervise the project.PrEfiNE project will evaluate an action plan focused on improving FD knowledge to make necessary recommendations for an early recognition of the disease. In addition will generate a plan to improve previously undetected needs.
Prevalence of the protein-energy wasting syndrome and its association with mortality in haemodialysis patients in a centre in Spain [Prevalencia del síndrome de desgaste proteico-energético y su asociación con mortalidad en pacientes en hemodiálisis en un centro en españa]
Gracia-Iguacel C.,Servicio de Nefrologia |
Gonzalez-Parra E.,Servicio de Nefrologia |
Perez-Gomez M.V.,Servicio de Nefrologia |
Mahillo I.,Servicio de Nefrologia |
And 3 more authors.
Nefrologia | Year: 2013
Introduction: Malnutrition has been described in patients with chronic kidney disease as well as its association with cardiovascular risk and mortality in haemodialysis patients. Recently, the new term 'protein energy wasting' has been proposed with new diagnostic criteria (biochemical and anthropometric markers) for early identification of patients at risk for protein energy wasting and mortality. The aim of this study was to examine the prevalence, evolution over time and prognostic significance of PEW in a Spanish dialysis centre for the first time in Spain. Patients and methods: an observational study that included 122 prevalent haemodialysis patients at our centre. Between January 2010 and October 2012, three visits were carried out in which clinical, biochemical, anthropometric and body composition parameters were collected using BIS (bioelectrical impedance spectroscopy) along with their respective dialytic characteristics, in accordance with the criteria of the new definition. We analysed the prevalence of PEW in each visit, progression of the malnutrition parameters and factors potentially associated with PEW. After a mean followup period of 461 days, we analysed survival. Statistical analysis was performed using the R software. Results: The prevalence of PEW remained constant over time: 37% at baseline visit, 40.5% at 12 months and 41.1% at 24 months. With the introduction of the dynamic variable muscle mass loss, included in the definition of PEW, prevalence increased to 50% at 24 months. The PEW situation is dynamic, as demonstrated by the fact that 26%-36% of patients without PEW develop it de novo each year and 12%-30% annually recover from this situation. The presence of PEW was associated with higher rates of resistance to erythropoietin (irEPO) and higher pulse pressure at the end of dialysis. In the multivariable regression model, PEW predictive clinical variables were over-hydration, irEPO, intracellular water and the extracellular water/intracellular water ratio. Twenty-six (21%) patients died. The Kaplan-Meier curve did not show any differences in mortality risk between patients with and those without PEW, but the loss of muscle mass was associated with increased mortality. Conclusion: The present observational study highlights the high prevalence of PEW, which has a dynamic nature in haemodialysis patients. Only the criterion of muscle mass loss (increased protein catabolism) was associated with increased mortality, while the other PEW criteria according to the ISRNM classification were not associated with increased mortality. We also observed a state of over-hydration in patients with PEW. This state of over-hydration (increased extracellular water due to occupation of muscle loss without an increase in total body water) cannot be evaluated by dry weight or the body mass index. Intervention studies are necessary in order to assess whether or not the prevention of sarcopaenia improves survival © 2013 Revista Nefrología. órgano Oficial de la Sociedad Española de Nefrología.
Gadola L.,University of the Republic of Uruguay |
Pogg C.,Servicio de Nefrologia |
Poggio M.,Servicio de Nefrologia |
Saez L.,University of the Republic of Uruguay |
And 6 more authors.
Peritoneal Dialysis International | Year: 2013
Objectives: The present study evaluated the tool used to assess patients' skills and the impact on peritonitis rates of a new multidisciplinary peritoneal dialysis (PD) education program (PDEP). Methods: After the University Hospital Ethics Committee approved the study, the educational and clinical records of PD patients were retrospectively analyzed in two phases. In phase I, an Objective Structured Assessment (OSA) was used during August 2008 to evaluate the practical skills of 25 patients with adequate Kt/V and no mental disabilities who had been on PD for more than 1 month. Test results were correlated with the prior year's peritonitis rate. In phase II, the new PDEP, consisting of individual lessons, a retraining schedule, and group meetings, was introduced starting 1 September 2008. Age, sex, years of education, time on PD, number of training sessions, and peritonitis episodes were recorded. Statistical analyses used t-tests, chi-square tests, and Poisson distributions; a p value of less than 0.05 was considered significant. Results: In phase I, 25 patients [16 men, 9 women; mean age: 54 ± 15 years (range: 22 - 84 years); mean time on PD: 35 ± 30 months (range: 1 - 107 months)] were studied. The OSA results correlated with peritonitis rates: patients who passed the test had experienced significantly lower peritonitis rates during the prior year (p < 0.05). In phase II, after the new PDEP was introduced, overall peritonitis rates significantly declined (to 0.28 episodes/patient-year from 0.55 episodes/patient-year, p < 0.05); the Staphylococcus peritonitis rate also declined (to 0.09 episodes/patient-year from 0.24 episodes/patient-year, p < 0.05). Conclusions: The OSA is a reliable tool for assessing patients' skills, and it correlates with peritonitis rates. The multidisciplinary PDEP significantly improved outcomes by further lowering peritonitis rates. © 2013 International Society for Peritoneal Dialysis.
PubMed | Servicio de Anatomia Patologica and Servicio de Nefrologia
Type: Journal Article | Journal: Transplantation proceedings | Year: 2016
Antibody-mediated rejection is the main cause of deterioration of kidney transplants and frequently is detected only by means of protocol biopsies. The aim of this study was to relate the presence of albuminuria throughout the 1st year to the histologic findings detected by 1-year protocol biopsies in kidney graft recipients.Retrospective observational study of 86 protocol biopsies 1 year after transplantation. Albuminuria was measured at 3, 6, 9, and 12 months in urine samples and expressed as albumin/creatinine (mg/g).Analysis of biopsies, reflected according to the Banff criteria, the following categories: fibrosis and tubular atrophy, 35 (40.7%); cellular rejection, 13 (15.1%); antibody-mediated rejection, 8 (9.3%); chronic glomerulopathy, 10 (11.6%); normal, 14 (16.3%); recurrence, 1 (1.2%); and other, 5 (5.8%). The proportions of patients with albuminuria for Banff scale scores (0 vs1, respectively) at 6 and 12 months, respectively, after transplantation, were: for marker glomerulitis, 45.5% versus 59.3% (P= .021) and 36.4% versus 70.4% (P< .001); for marker glomerulopathy, 49.1% versus 50.0% (P= .051) and 42.1% versus 58.3% (P= .019); for marker peritubular capillaritis, 45.8% versus 60.9% (P= .047) and 39.0% versus 69.6% (P= .276); and for marker C4d, 49.2% versus 56.3% (P= .894) and 46.2% versus 56.3% (P= .774).The presence of albuminuria after renal transplantation is common, especially in patients with proteinuria. Persistent albuminuria after transplantation, even at low levels, can be indicative of subclinical antibody-mediated rejection. Additional broader studies to relate the albuminuria to histologic changes observed in protocol biopsies are required.