Juan Antonio Moreno

Hospital General Universitario Gregorio Marañón, Madrid, Madrid, Spain

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Publications (35)134.31 Total impact

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    ABSTRACT: Haematuria has long been considered to be a benign condition associated with glomerular diseases. However, new evidences suggest that haematuria has a pathogenic role in promoting kidney disease progression. An increased risk for end-stage renal disease has been reported in adolescents and young adults with persistent microscopic haematuria. A persistent impairment of renal function has been also reported following macroscopic haematuria-associated acute kidney injury in immunoglobulin A nephropathy. Haematuria-induced renal damage has been related to oxidant, cytotoxic and inflammatory effects induced by haemoglobin or haem released from red blood cells. The pathophysiological origin of haematuria may be due to a more fragile and easily ruptured glomerular filtration barrier, as reported in several glomerular diseases. In this review we describe a number of the key issues associated with the epidemiology and pathogenesis of haematuria-associated diseases, provide an update of recent knowledge on the role of haematuria on renal function outcome and discuss specific therapeutic approaches in this setting. 1. Glomerular haematuria is a common observation in a number of renal diseases that may lead to persistent renal injury. 2. Haematuria in children differs from that in adults in specific aspects, particularly in the frequency of glomerular diseases and renal disease outcome. 3. Regular follow-up of renal function in children with isolated microhaematuria may be recommended.
    Pediatric Nephrology 05/2015; DOI:10.1007/s00467-015-3119-1 · 2.88 Impact Factor
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    ABSTRACT: Haematuria was known as a benign hallmark of some glomerular diseases, but over the last decade, new evidences pointed its negative implications on kidney disease progression. Cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury observed in human biopsy specimens. However, the precise mechanisms responsible for haematuria remain unclear. The presence of red blood cells (RBCs) with irregular contours and shape in the urine indicates RBCs egression from the glomerular capillary into the urinary space. Therefore glomerular haematuria may be a marker of glomerular filtration barrier dysfunction or damage. In this review we describe some key issues regarding epidemiology and pathogenesis of haematuric diseases as well as their renal morphological findings.
    05/2015; 4(2):185-95. DOI:10.5527/wjn.v4.i2.185
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    ABSTRACT: Patients infected with the human immunodeficiency virus (HIV) have an increased cardiovascular risk. Although initially this increased risk was attributed to metabolic alterations associated with antiretroviral treatment, in recent years, the attention has been focused on the HIV disease itself. Inflammation, immune system activation, and endothelial dysfunction facilitated by HIV infection have been identified as key factors in the development and progression of atherosclerosis. In this review, we describe the epidemiology and pathogenesis of cardiovascular disease in patients with HIV infection and summarize the latest knowledge on the relationship between traditional and novel inflammatory, immune activation, and endothelial dysfunction biomarkers on the cardiovascular risk associated with HIV infection.
    Vascular Health and Risk Management 01/2015; 11:35-48. DOI:10.2147/VHRM.S65885
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    ABSTRACT: Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV. The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects. Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations. HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART.
    PLoS ONE 03/2014; 9(3):e90541. DOI:10.1371/journal.pone.0090541 · 3.53 Impact Factor
  • Clinical nephrology 01/2014; 81(03):203-209. DOI:10.5414/CN107520 · 1.23 Impact Factor
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    ABSTRACT: Klotho is a renal protein with anti-aging properties that is downregulated in conditions related to kidney injury. Hyperlipidemia accelerates the progression of renal damage, but the mechanisms of the deleterious effects of hyperlipidemia remain unclear. We evaluated whether hyperlipidemia modulates Klotho expression in kidneys from C57BL/6 and hyperlipidemic apolipoprotein E knockout (ApoE KO) mice fed with a normal chow diet (ND) or a Western-type high cholesterol-fat diet (HC) for 5 to 10 weeks, respectively. In ApoE KO mice, the HC diet increased serum and renal cholesterol levels, kidney injury severity, kidney macrophage infiltration and inflammatory chemokine expression. A significant reduction in Klotho mRNA and protein expression was observed in kidneys from hypercholesteromic ApoE KO mice fed a HC diet as compared with controls, both at 5 and 10 weeks. In order to study the mechanism involved in Klotho down-regulation, murine tubular epithelial cells were treated with ox-LDL. Oxidized-LDL were effectively uptaken by tubular cells and decreased both Klotho mRNA and protein expression in a time- and dose-dependent manner in these cells. Finally, NF-κB and ERK inhibitors prevented ox-LDL-induced Klotho downregulation. Our results suggest that hyperlipidemia-associated kidney injury decreases renal expression of Klotho. Therefore, Klotho could be a key element explaining the relationship between hyperlipidemia and aging with renal disease.
    PLoS ONE 12/2013; 8(12):e83713. DOI:10.1371/journal.pone.0083713 · 3.53 Impact Factor
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    ABSTRACT: Background: Macroscopic hematuria (MH) may cause acute kidney injury (AKI) in IgA nephropathy. Up to 25% of patients with MH-associated AKI do not recover baseline renal function. Our objective was to identify subjects at high risk for an adverse renal function. Methods: We examined macrophages, oxidative stress markers (NADPH-p22 and HO-1) and the hemoglobin scavenger receptor (CD163) in renal biopsy specimens from 33 MH-AKI patients with complete recovery (CR, n = 17) or incomplete recovery (IR, n = 16) of renal function after 6.72 (range 0.5-21.5) years of follow-up. Results: CD163-expressing macrophages, HO-1 and NADPH-p22 expression were located in areas surrounding tubules with iron deposits and filled with erythrocyte casts. CD163-positive macrophages score and HO-1- and p22-positive staining correlated positively with percentage of tubules with erythrocyte casts and tubular necrosis. Macrophage infiltration, CD163-positive macrophage score, NADPH-p22- and HO-1-positive staining areas were significantly greater in IR patients when compared with CR patients. The CD163-positive macrophage score and oxidative stress markers (p22 and HO-1) were negatively correlated with renal function outcome, as determined by estimated glomerular filtration rate (eGFR) and proteinuria, at the end of the follow-up period. In multivariate analysis, the CD163-positive macrophage score remained significantly associated with final eGFR and proteinuria after adjustment by age, gender, duration of MH, initial eGFR and proteinuria. Conclusions: Increased macrophage infiltration, CD163 expression and oxidative stress are significant prognostic factors for an IR of renal function in patients with MH-associated AKI. These molecular pathways may be involved in the renal response to injury and could be useful to improve diagnosis and therapeutics.
    Nephron Clinical Practice 10/2012; 121(1):c42-c53. DOI:10.1159/000342385 · 1.65 Impact Factor
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    ABSTRACT: INTRODUCTION: Proteinuria is a common finding in glomerular diseases that contributes to the progression of chronic kidney injury. Tubular cells reabsorb the excess of albumin and other plasma proteins from the tubular lumen, triggering several pathophysiologic responses, such as overexpression of fibrogenic mediators and inflammatory chemokines. Chemokines are implicated both in the recruitment of inflammatory infiltrate and in a number of physiological and pathological processes related to protein overload. AREAS COVERED: In recent years, the specific chemokines and their receptors and the intracellular signaling pathways involved in proteinuria-induced renal damage have been identified. This review provides an overview of the role of chemokines and their receptors in proteinuria-related renal disease and summarizes novel therapeutic approaches to restrain the progression of renal damage. EXPERT OPINION: Inhibition of chemokine-induced biological activities is a promising therapeutic strategy in proteinuric disorders. Neutralizing antibodies and small organic molecules targeting chemokines and chemokine receptors have been proven to prevent inflammation and renal damage in experimental models of protein overload. Some of these compounds are currently being tested in human clinical trials.
    Expert Opinion on Therapeutic Targets 08/2012; 16(8):833-45. DOI:10.1517/14728222.2012.703657 · 4.90 Impact Factor
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    ABSTRACT: Haematuria is a frequent manifestation of glomerular disease. However, nephrologists devote more attention to the monitoring and therapeutic targeting of another key manifestation of glomerular injury, proteinuria. Recent reports have propelled haematuria to the forefront of clinical nephrology. Thus, glomerular macroscopic haematuria is associated with the development of acute kidney injury (AKI) with predominant tubular cell damage and there is increasing evidence for the negative impact of glomerular haematuria-associated AKI on long-term renal function outcome both in the context of IgA nephropathy and in anticoagulated patients. In addition, an epidemiological association between isolated microscopic haematuria in young adults and long-term incidence of end-stage renal disease has been described. Finally, a clearer understanding of how haematuria may cause tubular injury is emerging through detailed histological assessment of human biopsies and experimental models of haemoglobin-mediated nephrotoxicity.
    Nephrology Dialysis Transplantation 01/2012; 27(1):28-34. DOI:10.1093/ndt/gfr749 · 3.49 Impact Factor
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    ABSTRACT: Hematuria is a common finding in various glomerular diseases. This article reviews the clinical data on glomerular hematuria and kidney injury, as well as the pathophysiology of hematuria-associated renal damage. Although glomerular hematuria has been considered a clinical manifestation of glomerular diseases without real consequences on renal function and long-term prognosis, many studies performed have shown a relationship between macroscopic glomerular hematuria and AKI and have suggested that macroscopic hematuria-associated AKI is related to adverse long-term outcomes. Thus, up to 25% of patients with macroscopic hematuria-associated AKI do not recover baseline renal function. Oral anticoagulation has been associated with glomerular macrohematuria-related kidney injury. Several pathophysiologic mechanisms may account for the tubular injury found on renal biopsy specimens. Mechanical obstruction by red blood cell casts was thought to play a role. More recent evidence points to cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells. These mechanisms of injury may be shared with hemoglobinuria or myoglobinuria-induced AKI. Heme oxygenase catalyzes the conversion of heme to biliverdin and is protective in animal models of heme toxicity. CD163, the recently identified scavenger receptor for extracellular hemoglobin, promotes the activation of anti-inflammatory pathways, opening the gates for novel therapeutic approaches.
    Clinical Journal of the American Society of Nephrology 11/2011; 7(1):175-84. DOI:10.2215/CJN.01970211 · 5.25 Impact Factor
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    ABSTRACT: Decreased renal function has been observed in diseases with intravascular haemolysis, including paroxysmal nocturnal haemoglobinuria (PNH). However, the mechanisms via which haemoglobin enhances renal damage in this pathology are not fully known. We report a case of acute renal failure associated to PNH and extensive haemosiderin deposits in tubular cells. Renal biopsy also revealed a strong immunostaining of CD163 (a haemoglobin scavenger receptor expressed in macrophages) and oxidative stress markers (NADPH-p22 phox and haeme oxigenase-1) in areas with deposits of iron. This fact provides evidence for a pathogenic role for free haemoglobin in tubulointerstitial renal injury in human PNH disease.
    Nephrology Dialysis Transplantation 07/2011; 26(10):3408-11. DOI:10.1093/ndt/gfr391 · 3.49 Impact Factor
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    ABSTRACT: CD163 is a macrophage receptor for haemoglobin-haptoglobin (Hb-Hp) complexes, responsible for the clearance of haemoglobin. We hypothesized that production of soluble CD163 (sCD163) may be due to proleolytic shedding of membrane CD163 by neutrophil elastase, reported to be increased in culprit atherosclerotic plaques. We analysed the relationship between CD163 solubilization and elastase in vitro, in macrophage culture, ex vivo in human atherosclerotic plaque samples, and in vivo, in plasma of patients with coronary artery disease. Neutrophil elastase was shown to enhance CD163 shedding and to decrease the uptake of Hb-Hp complexes by cultured macrophages. In addition, cultured carotid endarterectomy samples showing features of intraplaque haemorrhage released more sCD163 and elastase/α1-antitrypsin (α1-AT) complexes than non-haemorrhagic plaques (n= 44). Plasma levels of sCD163 and neutrophil elastase (complexed with α1-AT) were measured in patients with an acute coronary syndrome (ACS, n= 42), stable angina pectoris (SAP, n= 28), or normal coronary angiograms without subclinical atherosclerosis (n= 21). Acute coronary syndrome patients had higher sCD163 and elastase/α1-AT complexes plasma concentrations than subjects without coronary atherosclerosis. Circulating sCD163 and elastase/α1-AT complexes were positively correlated in patients with ACS (r = 0.56, P< 0.0002) and SAP (r = 0.62, P< 0.0005). Our results suggest that neutrophil elastase promotes CD163 shedding, resulting in a decreased clearance of Hb by macrophages, which may favour plaque destabilization. This may be reflected by increased plasma levels of sCD163 and elastase/α1-AT complexes which are positively correlated in patients with coronary artery disease.
    European Heart Journal 05/2011; 33(2):252-63. DOI:10.1093/eurheartj/ehr123 · 14.72 Impact Factor
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    ABSTRACT: Macroscopic haematuria of glomerular origin has been associated with acute kidney injury. We report a patient with IgA nephropathy, macroscopic haematuria and acute kidney injury. Systemic anticoagulation may have aggravated haematuria. There was extensive interstitial and intratubular red blood cell extravasation, and interstitial haemosiderin deposits. The abundant presence of macrophages expressing the haemoglobin scavenger receptor CD163 and of cells stained for oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) in areas of interstitial haemorrhage and red blood cell cast-containing tubules provided evidence for a role for free haemoglobin in tubulointerstitial renal injury in human glomerular disease.
    Nephrology Dialysis Transplantation 12/2010; 25(12):4103-6. DOI:10.1093/ndt/gfq493 · 3.49 Impact Factor
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    ABSTRACT: The NF-kappaB family of transcription factors regulates the induction and resolution of inflammation. Two main pathways, classical and alternative, control the nuclear translocation of NF-kappaB. Classical NF-kappaB activation is usually a rapid and transient response to a wide range of stimuli whose main effector is RelA/p50. The alternative NF-kappaB pathway is a more delayed response to a smaller range of stimuli resulting in DNA binding of RelB/p52 complexes. Additional complexity in this system involves the posttranslational modification of NF-kappaB proteins and an ever-increasing range of co-activators, co-repressors, and NF-kappaB complex proteins. Collectively, NF-kappaB regulates the expression of numerous genes that play a key role in the inflammatory response during human and experimental kidney injury. Multiple stimuli activate NF-kappaB through the classical pathway in somatic renal cells, and noncanonical pathway activation by TWEAK occurs in acute kidney injury. Under most test conditions, specific NF-kappaB inhibitors tend to reduce inflammation in experimental kidney injury but not always. Although many drugs in current use clinically influence NF-kappaB activation, there are no data regarding specific NF-kappaB inhibition in human kidney disease.
    Journal of the American Society of Nephrology 08/2010; 21(8):1254-62. DOI:10.1681/ASN.2010020218 · 9.47 Impact Factor
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    ABSTRACT: Soluble TNF-like weak inducer of apoptosis (sTWEAK) and long pentraxin-3 (PTX3) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). This study tested the hypothesis that the improvement in endothelial function after initiation of angiotensin II receptor blocker (valsartan), calcium channel blocker (amlodipine) therapy, or a combination of both is directly linked to the normalization of sTWEAK and PTX3. One-hundred-eight diabetic CKD stage I patients with hypertension (56% men, 46.7+/-5.3 years) were allocated to a 12-week intervention with amlodipine (10 mg/d), valsartan (160 mg/d), or their combination. Plasma levels of sTWEAK, PTX3, and flow-mediated dilation (FMD) were studied during the interventions. All treatment strategies effectively increased FMD and reduced proteinuria, confirming a more prone reduction with the combined therapy. These improvements were followed by significant PTX3 reductions. Valsartan alone and in combination with amlodipine achieved significant incremental raises in sTWEAK plasma levels. More importantly, the changes observed in sTWEAK (beta=0.25, P=0.006) or PTX3 (beta=-0.24, P=0.007) plasma levels were independently associated with the improvement in ultrasonographically measured FMD. This study shows that treatment with antihypertensive drugs improves FMD and normalizes proteinuria, PTX3, and sTWEAK in diabetic CKD stage I patients with hypertension. The improvement in FMD was independently associated with PTX3 and sTWEAK normalization. Two surrogate biomarkers of endothelial function are therefore identified with potential as therapeutic targets. The study was registered in clinicaltrials.gov as NCT00921570.
    Clinical Journal of the American Society of Nephrology 07/2010; 5(7):1174-81. DOI:10.2215/CJN.01110210 · 5.25 Impact Factor
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    ABSTRACT: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of cytokines. TWEAK binds and activates the Fn14 receptor, and may regulate apoptosis, inflammation, and angiogenesis, in different pathological conditions. We have evaluated the effect of exogenous TWEAK administration as well as the role of endogenous TWEAK on proinflammatory cytokine expression and vascular and renal injury severity in hyperlipidemic ApoE-knockout mice. ApoE(-/-) mice were fed with hyperlipidemic diet for 4 to 10 weeks, then randomized and treated with saline (controls), TWEAK (10 microg/kg/d), anti-TWEAK neutralizing mAb (1000 microg/kg/d), TWEAK plus anti-TWEAK antibody (10 microg TWEAK +1000 microg anti-TWEAK/kg/d), or nonspecific IgG (1000 microg/kg/d) daily for 9 days. In ApoE(-/-) mice, exogenous TWEAK administration in ApoE(-/-) mice induced activation of NF-kappaB, a key transcription factor implicated in the regulation of the inflammatory response, in vascular and renal lesions. Furthermore, TWEAK treatment increased chemokine expression (RANTES and MCP-1), as well as macrophage infiltration in atherosclerotic plaques and renal lesions. These effects were associated with exacerbation of vascular and renal damage. Conversely, treatment of ApoE(-/-) mice with an anti-TWEAK blocking mAb decreased NF-kappaB activation, proinflammatory cytokine expression, macrophage infiltration, and vascular and renal injury severity, indicating a pathological role for endogenous TWEAK. Finally, in murine vascular smooth muscle cells or tubular cells, either ox-LDL or TWEAK treatment increased expression and secretion of both RANTES and MCP-1. Furthermore, ox-LDL and TWEAK synergized for induction of MCP-1 and RANTES expression and secretion. Our results suggest that TWEAK exacerbates the inflammatory response associated with a high lipid-rich diet. TWEAK may be a novel therapeutic target to prevent vascular and renal damage associated with hyperlipidemia.
    Arteriosclerosis Thrombosis and Vascular Biology 09/2009; 29(12):2061-8. DOI:10.1161/ATVBAHA.109.194852 · 5.53 Impact Factor
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    ABSTRACT: TWEAK is a cytokine of the TNF superfamily that activates the Fn14 receptor. TWEAK may regulate cell proliferation, cell death, cell differentiation, angiogenesis and inflammation. The expression of TWEAK and Fn14 is increased during vascular and renal injury. Inflammatory cytokines increase Fn14 receptor expression in tubular and vascular smooth muscle cells. Moreover, TWEAK induces tubular cell apoptosis under proinflammatory conditions. TWEAK itself contributes to renal and vascular inflammation by promoting chemokine and inflammatory cytokine secretion. Confirmation of its role in acute kidney injury and atherosclerotic lesions formation came from functional studies in experimental animal models. The available evidence suggests that TWEAK might be a target for therapeutic intervention in renal and vascular injury and its role in different forms of tissue damage should be further explored.
    Cytokine & growth factor reviews 07/2009; 20(3):251-8. DOI:10.1016/j.cytogfr.2009.05.002 · 6.54 Impact Factor
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    ABSTRACT: The interindividual variation in ApoE plasma concentration is considerable, mainly determined by apoE genotype and sex. However, a large amount of variability remains unexplained by these factors. We have evaluated whether the quantity and quality of dietary fat interacts with the apoE genotype and sex modifying ApoE plasma levels in young healthy subjects. Eighty-four volunteers (sixty-six apoE3/3, eight apoE4/3 and ten apoE3/2) were subjected to three dietary periods, each lasting 4 weeks. The first was a SFA-enriched diet (38 % fat and 20 % SFA), which was followed by a carbohydrate (CHO)-rich diet (30 % fat, < 10 % SFA and 55 % carbohydrate) or a MUFA-rich diet (38 % fat and 22 % MUFA) following a randomised crossover design. apoE2 carriers have the highest ApoE levels, whereas apoE4 individuals show the lowest concentration after the SFA, CHO and MUFA diets. Women had significantly higher ApoE concentration than men only after the consumption of the SFA diet. The SFA diet increased the ApoE plasma concentration when compared with the CHO- and MUFA-rich diets in women, but not in men. In women, but not in men, the shift from the SFA- to CHO- or MUFA-rich diets significantly decreased the ApoE concentration in apoE3/2 and apoE3/3 subjects, whereas no differences were observed in women with the apoE4/3 genotype. Sex and apoE genotype determine ApoE plasma levels; however, this effect is dependent on dietary fat.
    The British journal of nutrition 12/2008; 101(12):1745-52. DOI:10.1017/S0007114508111515 · 3.34 Impact Factor
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    ABSTRACT: Recent advances have identified the podocyte as a key target in glomerular injury. The podocyte is a highly specialized cell which is responsible for the glomerular permselectivity for proteins in the kidney. Podocyte injury or loss leads to proteinuria. Apoptosis has been shown to contribute to renal cell loss, including loss of podocytes. The most striking feature of the podocyte is its ability to form intricate specialized cell junctions, the slit diaphragm. Slit diaphragm proteins play an important role in podocyte biology, protein permselectivity, cell signalling and disease. This review focuses on recent advances on the understanding of podocyte survival regulation, its relationship to slit diaphragm structure and function, and how this knowledge may affect our therapeutic approach to proteinuric kidney disease.
    Current Medicinal Chemistry 02/2008; 15(16):1645-54. DOI:10.2174/092986708784911542 · 3.72 Impact Factor
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    ABSTRACT: TWEAK is a recently identified cytokine of the TNF superfamiliy. Through activation of the Fn14 receptor, TWEAK regulates cell proliferation, cell death and inflammation. Recent studies show increased TWEAK and Fn14 expression in tubular cells during acute kidney injury as well as elevated urinary TWEAK levels in patients with active lupus nephritis. Furthermore, glomerular mesangial cells and renal tubular epithelial cells express the Fn14 receptor under the regulation of proinflammatory cytokines. TWEAK weakly increases cell death and promotes secretion of inflammatory mediators in non-stimulated mesangial cells. In addition, in a proinflammatory milieu, TWEAK induces apoptosis of mesangial and tubular cells. The available data suggest that TWEAK is a new player in kidney injury both at the glomerular and tubulointerstitial levels and might be a target for therapeutic intervention.
    Frontiers in Bioscience 02/2008; 13:580-9. DOI:10.2741/2703 · 4.25 Impact Factor

Publication Stats

494 Citations
134.31 Total Impact Points

Institutions

  • 2015
    • Hospital General Universitario Gregorio Marañón
      • Department of Nephrology
      Madrid, Madrid, Spain
  • 2010–2015
    • Fundación Jiménez Díaz
      Madrid, Madrid, Spain
  • 2008–2012
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
  • 2003–2008
    • Hospital Universitario Reina Sofía
      Cordoue, Andalusia, Spain
  • 2006
    • University of Cordoba (Spain)
      Cordoue, Andalusia, Spain
  • 2005
    • Tufts University
      Бостон, Georgia, United States