Rodrigues Diez R.,Autonomous University of Madrid |
Rodrigues-Diez R.,Autonomous University of Madrid |
Lavoz C.,Autonomous University of Madrid |
Rayego-Mateos S.,Autonomous University of Madrid |
And 6 more authors.
PLoS ONE | Year: 2010
We have recently described that in an experimental model of atherosclerosis and in vascular smooth muscle cells (VSMCs) statins increased the activation of the Smad pathway by transforming growth factor-b (TGF-β), leading to an increase in TGF-β-dependent matrix accumulation and plaque stabilization. Angiotensin II (AngII) activates the Smad pathway and contributes to vascular fibrosis, although the in vivo contribution of TGF-β has not been completely elucidated. Our aim was to further investigate the mechanisms involved in AngII-induced Smad activation in the vasculature, and to clarify the beneficial effects of statins on AngII-induced vascular fibrosis. Infusion of AngII into rats for 3 days activates the Smad pathway and increases fibrotic-related factors, independently of TGF-β, in rat aorta. Treatment with atorvastatin or simvastatin inhibited AngII-induced Smad activation and related-fibrosis. In cultured rat VSMCs, direct AngII/Smad pathway activation was mediated by p38 MAPK and ROCK activation. Preincubation of VSMCs with statins inhibited AngII-induced Smad activation at all time points studied (from 20 minutes to 24 hours). All these data show that statins inhibited several AngII-activated intracellular signaling systems, including p38-MAPK and ROCK, which regulates the AngII/Smad pathway and related profibrotic factors and matrix proteins, independently of TGF-β responses. The inhibitory effect of statins on the AngII/Smad pathway could explain, at least in part, their beneficial effects on hypertension-induced vascular damage. © 2010 Rodrigues-Diez et al.
Rodrigues-Diez R.,Cellular Biology in Renal Diseases Laboratory |
Lavoz C.,Cellular Biology in Renal Diseases Laboratory |
Carvajal G.,Cellular Biology in Renal Diseases Laboratory |
Rayego-Mateos S.,Cellular Biology in Renal Diseases Laboratory |
And 5 more authors.
Nephron - Experimental Nephrology | Year: 2013
Background/Aims: Chronic kidney disease is characterized by accumulation of extracellular matrix in the tubulointerstitial area. Fibroblasts are the main matrix-producing cells. One source of activated fibroblasts is the epithelial mesenchymal transition (EMT). In cultured tubular epithelial cells, transforming growth factor-β (TGF-β1) induced Gremlin production associated with EMT phenotypic changes, and therefore Gremlin has been proposed as a downstream TGF-β1 mediator. Gremlin is a developmental gene upregulated in chronic kidney diseases associated with matrix accumulation, but its direct role in the modulation of renal fibrosis and its relation with TGF-β has not been investigated. Methods: Murine renal fibroblasts and human tubular epithelial cells were studied. Renal fibrosis was determined by evaluation of key profibrotic factors, extracellular matrix proteins (ECM) and EMT markers by Western blot/confocal microscopy or real-time PCR. Endogenous Gremlin was targeted with small interfering RNA. Results: In murine fibroblasts, stimulation with recombinant Gremlin upregulated profibrotic genes, such as TGF-β1, and augmented the production of ECM proteins, including type I collagen. The blockade of endogenous Gremlin with small interfering RNA inhibited TGF-β1-induced ECM upregulation. In tubular epithelial cells Gremlin also increased profibrotic genes and caused EMT changes: phenotypic modulation to myofibroblast-like morphology, loss of epithelial markers and in-duction of mesenchymal markers. Moreover, Gremlin gene silencing inhibited TGF-β1-induced EMT changes. Conclusions: Gremlin directly activates profibrotic events in cul-tured renal fibroblasts and tubular epithelial cells. Moreover, endogenous Gremlin blockade inhibited TGF-β-mediated matrix production and EMT, suggesting that Gremlin could be a novel therapeutic target for renal fibrosis. © 2013 S. Karger AG, Basel.
News Article | October 27, 2016
BUFFALO, N.Y. - A study by University at Buffalo researchers has shown that physicians in pediatric intensive care units are not using the newest guidelines to diagnose acute kidney injury (AKI) in critically ill children, a practice that could affect their patients' long-term health. A pediatric critical care physician who focuses on acute kidney injury, Amanda Hassinger surveyed colleagues in her field on practice patterns related to the diagnosis and treatment of AKI, a condition that affects about 15 percent of critically ill children. The prevalence of AKI among patients in pediatric intensive care units is on the rise, which, she says, lends more urgency to gauging the current state of AKI management in pediatric intensive care units (PICUs). The results were discouraging, Hassinger reports in a recent paper in the journal Pediatric Critical Care Medicine. "What we found was pretty surprising. It was scarier than I thought in terms of how aware other physicians in my field are to the new guidelines for treatment of AKI and the new methods to diagnosis earlier and more effectively," said Hassinger, MD, MS, lead author on the paper, published in the journal's August issue. She wrote it while working on her master's degree in epidemiology/clinical research in UB's School of Public Health and Health Professions. Hassinger has been an attending physician in the Division of Critical Care at Women & Children's Hospital of Buffalo, and is also an assistant professor of pediatrics in UB's Jacobs School of Medicine and Biomedical Sciences and a member of UBMD Pediatrics. Hassinger and her co-authors surveyed 170 pediatric critical care physicians from academic centers, the Pediatric Acute Lung Injury and Sepsis Investigators network and the pediatric branch of the Society of Critical Care Medicine. The survey consisted of more than two-dozen questions. Among them, researchers asked what criteria the physicians frequently rely on to diagnose acute kidney injury in young patients. Half of the respondents reported not using recent AKI guidelines or diagnostic criteria in clinical practice. Specifically, 74 percent of physicians said they diagnose AKI using serum creatinine and urine output only, despite the fact that newer, more reliable, tests are available. The problem with serum creatinine as a test for renal function, Hassinger says, is that it is not effective in children for detecting AKI. It can be affected by several other factors, including nutrition and muscle mass. Several new biomarkers have been discovered that aid in the diagnosis of AKI. Diagnosing AKI in children in clinical practice has also proven difficult because there is not a consensus definition of AKI in pediatric patients. Several guidelines and criteria are available, but there is a lack of knowledge among pediatric intensive care physicians about which ones to use, leading to variability in how children are treated in the ICU, according to Hassinger. "I wasn't surprised that the newer tests aren't being used, because they do cost a lot of money and require special machinery," Hassinger says. "But what really upset me was that physicians were happy with the status quo and weren't looking for a better biomarker for this critically important condition. The existing biomarkers are inadequate. That was disappointing." AKI occurs most frequently in patients who are already in the hospital. It can be caused by a number of health conditions, including sepsis, shock, trauma, exposure to medications that affect the kidneys, or major surgery. What's more, according to the National Kidney Foundation, one episode of AKI increases a patient's chances of developing other health problems -- such as kidney disease, stroke or heart disease -- later in life. In fact, Hassinger said, data now show that children who experience a single episode of AKI in the ICU have a 5o percent to 75 percent chance of having renal insufficiency for the rest of their life. "It's an important but silent issue that needs more attention," she says. "The kidneys are a very vulnerable set of organs and they're important to overall balance in the body, so we should be paying more attention to them than we do. Somebody has to fight for the little beans." "This study gives us an important picture of what practice looks like in pediatric ICUs, so that we can understand what is missing," said Jo Freudenheim, PhD, chair of epidemiology and environmental health in UB's School of Public Health and Health Professions, and a co-author on the paper. "We can now start to make renewed efforts to change practice and to improve care." Hassinger has an idea why AKI often goes underappreciated. "The kidneys are extremely resilient, and children are resilient, so even if you have the worst stage of acute kidney injury, despite the physician, the kidneys and the patient get better. There's not as much urgency to diagnose it and call it the right name because most of the time, no matter what name you call it, kids will bounce back pretty well," she said. Toward that point, the researchers' survey asked physicians if they were aware that AKI independently has increased morbidity and mortality. Twelve percent of the respondents -- a particularly high number, Hassinger says -- said either no or that they were unsure. Hassinger was also surprised to learn that just one-third of the PICU physicians surveyed said they refer a child who has AKI to a kidney specialist once the patient is discharged from the intensive care unit. That means that two-thirds of the respondents reported either rarely or never offering referrals. "So these patients go unmonitored for periods of time until the kidney issues manifest when they're teenagers and they get an infection or another injury that knocks out the kidneys completely, and then they're in renal failure at 18," Hassinger said. Hassinger is partnering with a colleague at Cincinnati Children's Hospital Medical Center for a second survey that will take a closer look at the relationship between fluid overload and acute kidney injury in ICU patients. Fluids, given through IVs, are used regularly in hospitalized children. Fluid overload can cause organs to fail, Hassinger said, explaining why that's another area of current medical practice that needs better scrutiny. Other investigators on the paper were Sudha Garimella, clinical assistant professor in the Department of Pediatrics in UB's Jacobs School of Medicine and Biomedical Sciences and medical director of the Pediatric Dialysis Unit at Women & Children's Hospital of Buffalo, and Brian Wrotniak of the Department of Pediatrics.
Egbi O.G.,Niger Delta University |
Egbi O.G.,Federal Medical Center |
Egbi O.G.,Dialysis Unit |
Ogunrin O.,University of Benin |
Oviasu E.,University of Benin
Annals of African Medicine | Year: 2015
Background: Chronic kidney disease (CKD) has become a public health concern and may be complicated by cognitive impairment (CI) contributing significantly to morbidity and poor prognosis. This hospital-based study aimed at determining the prevalence and the determinants of CI among CKD patients in Nigeria.Materials and Methods: A total of 190 CKD patients and a 100 healthy control subjects completed this cross-sectional study. Sociodemographic data and history of common clinical features of CKD were obtained with the use of interviewer administered semi-structured questionnaires. The six-item cognitive impairment test was used for assessment of cognitive function of patients and controls.Results: The prevalence of CI in Stages 3, 4, and 5 CKD patients were 24.0%, 41.6%, and 46.2%, respectively with overall prevalence of 35.3% while only 6.0% of controls had CI (P = 0.03). The most potent determinants of CI were low hematocrit (odds ratio [OR] =3.50), low serum bicarbonate levels (OR = 2.20), and high serum urea (OR = 2.11).Conclusion: CKD is associated with significant CI in Nigerian patients especially with progressive deterioration in renal function. There is a need for regular evaluation of CKD patients for cognitive deficits.
Scola C.L.,Dialysis Unit |
De Mutiis C.,Dialysis Unit |
Hewitt I.K.,Princess Margaret Hospital for Children |
Puccio G.,University of Palermo |
And 6 more authors.
Pediatrics | Year: 2013
Objective: To evaluate the yield, economic, and radiation costs of 5 diagnostic algorithms compared with a protocol where all tests are performed (ultrasonography scan, cystography, and late technetium99 dimercaptosuccinic acid scan) in children after the first febrile urinary tract infections. Methods: A total of 304 children, 2 to 36 months of age, who completed the diagnostic follow-up (ultrasonography, cystourethrography, and acute and late technetium99 dimercaptosuccinic acid scans) of a randomized controlled trial (Italian Renal Infection Study 1) were eligible. The guidelines applied to this cohort in a retrospective simulation were: Melbourne Royal Children's Hospital, National Institute of Clinical Excellence (NICE), top down approach, American Academy of Pediatrics (AAP), and Italian Society of Pediatric Nephrology. Primary outcomes were the yield of abnormal tests for each diagnostic protocol; secondary outcomes were the economic and radiation costs. Results: Vesicoureteral reflux (VUR) was identified in 66 (22%) children and a parenchymal scarring was identified in 45 (15%). For detection of VUR (47/66) and scarring (45/45), the top down approach showed the highest sensitivity (76% and 100%, respectively) but also the highest economic and radiation costs (€52 268. 624 mSv). NICE (19/66) and AAP (18/66) had the highest specificities for VUR (90%) and the Italian Society of Pediatric Nephrology had the highest specificity (20/45) for scars (86%). NICE would have been the least costly (€26 838) and AAP would have resulted in the least radiation exposure (42 mSv). Conclusions: There is no ideal diagnostic protocol following a first febrile urinary tract infection. An aggressive protocol has a high sensitivity for detecting VUR and scarring but carries high financial and radiation costs with questionable benefit. Copyright © 2013 by the American Academy of Pediatrics.
Gallieni M.,University of Milan |
Aiello A.,Dialysis Unit |
Tucci B.,University of Milan Bicocca |
Sala V.,University of Milan Bicocca |
And 3 more authors.
The Scientific World Journal | Year: 2014
Chronic noncommunicable diseases (NCDs) such as hypertension, atherosclerosis, acute myocardial infarction, stroke, diabetes, obesity, and chronic kidney disease are the major cause of death not only in high income, but also in medium and low income countries. Hypertension and diabetes, the most common causes of chronic kidney disease, are particularly common in southeast Asian Countries. Because early intervention can markedly slow the progression of these two killer diseases, assessment of their presence through screening and intervention program is a priority. We summarize here results of the screening activities and the perspectives of a noncommunicable diseases project started in West Bengal, India, in collaboration with the Institute for Indian Mother and Child (IIMC), a nongovernmental voluntary organization committed to promoting child and maternal health. We started investigating hypertension and chronic kidney disease with screen in school-age children and in adults >30 years old. We found a remarkable prevalence of hypertension, even in underweight subjects, in both children and adult populations. A glomerular filtration rate <60 mL/min was found in 4.1% of adult subjects significantly higher than that of 0.8% to 1.4% reported 10 years ago. Increased awareness and intervention projects to identify NCDs and block their progression are necessary in all countries. © 2014 Maurizio Gallieni et al.
News Article | November 3, 2016
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Malyszko J.,Medical University of Bialystok |
Malyszko J.S.,Medical University of Bialystok |
Kozminski P.,Dialysis Unit |
Koc-Zorawska E.,Medical University of Bialystok |
And 2 more authors.
Nephron - Clinical Practice | Year: 2010
Background: Neutrophil gelatinase-associated lipocalin (NGAL) binds small, iron-carrying molecules - siderophores. On the other hand, hepcidin is a small defensin-like peptide produced by hepatocytes, modulated in response to anaemia, hypoxia, or inflammation. We tested the hypothesis that NGAL may be related to hepcidin, not only to iron metabolism, in 182 prevalent haemodialysed patients. Methods: Iron status (iron, total iron-binding capacity, ferritin, total saturation of transferrin, TSAT), complete blood count, creatinine, albumin, serum lipids were assessed using standard laboratory methods. Soluble receptor of transferrin, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α, interleukin-6, prohepcidin, hepcidin and NGAL were measured in serum using commercially available kits. Results: Serum NGAL, prohepcidin, hepcidin levels were significantly higher in haemodialysed patients over healthy volunteers (579.11 ± 213.95 vs. 78.43 ± 32.21 ng/ml, p < 0.001, 320.54 ± 182.65 vs. 98.65 ± 34.32 ng/ml, p < 0.01, 155.30 ± 94.05 vs. 23.65 ± 12.76 ng/ml, p < 0.001, respectively). Serum NGAL correlated strongly with residual renal function (r = -0.54, p < 0.001), Kt/V (r = 0.41, p < 0.001), hepcidin (r = -0.28, p < 0.01), serum creatinine (r = 0.63, p < 0.001), iron (r = 0.25, p < 0.01), TSAT (r = 0.30, p < 0.001), ferritin (r = 0.33, p < 0.001), hsCRP (r = 0.32, p < 0.001). In multiple regression analysis, residual renal function, hepcidin, creatinine and hsCRP were predictors of serum NGAL in haemodialysed patients. Conclusions: NGAL is highly induced in dialysed patients. NGAL could reflect both kidney function and iron metabolism. Taking into account the antimicrobial properties of NGAL, further studies are needed to address the role of NGAL in iron metabolism and inflammation in renal failure. Copyright © 2010 S. Karger AG, Basel.
Malyszko J.,Medical University of Bialystok |
Malyszko J.S.,Medical University of Bialystok |
Levin-Iaina N.,Chaim Sheba Medical Center |
Koc-Zorawska E.,Medical University of Bialystok |
And 2 more authors.
International Urology and Nephrology | Year: 2012
Introduction: Hemojuvelin (HJV) is highly expressed in the liver, skeletal muscles, and heart, seems to play a role in iron absorption and release from cells, and has anti-inflammatory properties. Moreover, HJV plays an essential role in the regulation of hepcidin expression, specifically in the iron-sensing pathway. Hepcidin has emerged as a key regulator of iron homeostasis. In this study we tested for the first time the hypothesis that HJV is related to iron metabolism in hemodialysis (HD) patients. Methods: Iron status, complete blood count, and serum creatinine, albumin, and lipids were assessed, using standard laboratory methods. Serum levels of soluble transferrin receptor (sTFR), high-sensitivity CRP, IL-6, hepcidin, and HJV were measured using commercially available kits. Results: Serum HJV, hepcidin, ferritin, IL-6, hsCRP, and serum creatinine were significantly higher (all P < 0.001), whereas serum iron, sTFR, transferrin, hemoglobin, and erythrocyte count were significantly lower in HD patients, compared to healthy volunteers (all P < 0.001). In univariate analysis, HJV was strongly correlated (P < 0.001) with ferritin, transferrin saturation, and TIBC, as well as with hsCRP, hepcidin, Kt/V (P < 0.01) and residual renal function, the presence of diabetes, APKD, and coronary heart disease. Predictors of HJV level in multiple regression analysis were ferritin (beta value was 0.50, P = 0.00004) and transferrin saturation (beta value was 0.47, P = 0.0002), explaining 81% of the HJV variations. Conclusions: Serum HJV is elevated in HD patients and related predominantly to kidney function and iron metabolism. However, HJV is probably not correlated to inflammation. HJV appears to be a new player in iron metabolism in these patients. © 2011 The Author(s).
PubMed | Medical University of Bialystok and Dialysis Unit
Type: | Journal: International urology and nephrology | Year: 2017
Traditional anticoagulants used in intermittent hemodialysis (HD) are unfractionated heparin (UFH) and increasingly low molecular weight heparins (LMWHs). Repeated and prolonged exposure to UFH and/or LMWHs may further disturb hemostasis in uremic patients. Vascular adhesion protein-1 (VAP-1) is secreted by vascular smooth muscle cells, adipocytes and endothelial cells with functional monoamine oxidase activity and is elevated in atherosclerosis, diabetes mellitus and obesity. The aim of this study was to assess the effects of UFH and LMWHs on VAP-1 concentration in HD patients. The effects on single HD session on VAP-1 were also evaluated as well as VAP-1 levels in regard to type of renal replacement therapy.We studied 82 hemodialyzed patients (mean age 63years, dialysis vintage 59months) and 17 patients treated by means of hemodiafiltration (HDF) (mean age 59years, HD vintage 84months, HDF 7months). Patients were anticoagulated with enoxaparin (n=46), dalteparin (n=10), nadroparin (n=6) or UFH (n=20) during their HD sessions. VAP-1 was assessed using kits from BioVendor, Modrice, Czech Republic.Patients on HDF had significantly lower VAP-1 when compared with HD patients. We found that VAP-1 concentration in patients dialyzed by using LMWH or UFH was similar. There was no effect on HD session on VAP-1 concentration. Diabetic patients had higher serum VAP-1 than non-diabetic.HDF is associated with lower VAP-1 levels indicating less pronounced endothelial cell injury than hemodialysis. Type of heparin seems to have no effect on VAP-1 levels in hemodialyzed patients. However, the cross-sectional but not prospective design is a limitation of this study.