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      Biomarcadores en el síndrome nefrótico: algunos pasos más en el largo camino Translated title: Biological markers of nephrotic syndrome: a few steps forward in the long way

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          Abstract

          Uno de los retos a los que debe enfrentarse la nefrología moderna es el de identificar biomarcadores que se asocien a patrones anatomopatológicos o a mecanismos patogénicos definidos y permitan el diagnóstico no invasivo de la causa del síndrome nefrótico o establecer subgrupos pronósticos en cada tipo de enfermedad, prediciendo la respuesta al tratamiento y/o la aparición de recidivas. Los avances en el conocimiento de la patogenia de las distintas enfermedades causantes de síndrome nefrótico, sumados al progresivo desarrollo y estandarización de las técnicas de proteómica plasmática y urinaria, han permitido ir identificando un número creciente de moléculas que podrían ser útiles para los fines anteriormente mencionados. En el momento actual, los datos de muchos de los candidatos identificados, sobre todo mediante técnicas de proteómica, son todavía muy preliminares. En la presente revisión, se resume la evidencia disponible sobre las moléculas que en la actualidad cuentan con mayor evaluación en estudios clínicos.

          Translated abstract

          One of the major challenges modern nephrology should face is the identification of biomarkers that are associated with histopathological patterns or defined pathogenic mechanisms that might aid in the non-invasive diagnosis of the causes of nephrotic syndrome, or in establishing prognosis sub-groups based on each type of disease, thus predicting response to treatment and/or recurrence. Advancements in the understanding of the pathogenesis of the different diseases that cause nephrotic syndrome, along with the progressive development and standardisation of plasma and urine proteomics techniques, have facilitated the identification of a growing number of molecules that might be useful for these objectives. Currently, the available information for many of the possible candidates identified to date, above all those discovered using proteomics, are still very preliminary. In this review, we summarise the available evidence for the different molecules that have been best assessed using clinical studies.

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          Most cited references198

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          Lipid peroxidation and antioxidants as biomarkers of tissue damage.

          Disturbance of the balance between the production of reactive oxygen species such as superoxide; hydrogen peroxide; hypochlorous acid; hydroxyl, alkoxyl, and peroxyl radicals; and antioxidant defenses against them produces oxidative stress, which amplifies tissue damage by releasing prooxidative forms of reactive iron that are able to drive Fenton chemistry and lipid peroxidation and by eroding away protective sacrificial antioxidants. The body has a hierarchy of defense strategies to deal with oxidative stress within different cellular compartments, and superimposed on these are gene-regulated defenses involving the heat-shock and oxidant stress proteins.
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            Pathogenesis of lipoid nephrosis: a disorder of T-cell function.

            J Shalhoub (1974)
            Clinical observations suggest that lipoid nephrosis is produced by a systemic abnormality of T-cell function resulting in the secretion of a circulating chemical mediator toxic to an immunologically innocent glomerular basement membrane. The lack of evidence of a humoral antibody response, remission induced by measles which modifies cell-mediated immunity, the therapeutic benefits of steroids and cyclophosphamide which also abate cell-mediated responses, and the occurrence of this syndrome in Hodgkin's disease support this hypothesis. The susceptibility of untreated patients to pneumococcal infections may be of primary or secondary pathogenetic importance. Taken together, the data suggest that this syndrome is a clinical expression of a self-limited primary immune-deficiency disease.
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              Induction of B7-1 in podocytes is associated with nephrotic syndrome.

              Kidney podocytes and their slit diaphragms form the final barrier to urinary protein loss. This explains why podocyte injury is typically associated with nephrotic syndrome. The present study uncovered an unanticipated novel role for costimulatory molecule B7-1 in podocytes as an inducible modifier of glomerular permselectivity. B7-1 in podocytes was found in genetic, drug-induced, immune-mediated, and bacterial toxin-induced experimental kidney diseases with nephrotic syndrome. The clinical significance of our results is underscored by the observation that podocyte expression of B7-1 correlated with the severity of human lupus nephritis. In vivo, exposure to low-dose LPS rapidly upregulates B7-1 in podocytes of WT and SCID mice, leading to nephrotic-range proteinuria. Mice lacking B7-1 are protected from LPS-induced nephrotic syndrome, suggesting a link between podocyte B7-1 expression and proteinuria. LPS signaling through toll-like receptor-4 reorganized the podocyte actin cytoskeleton in vitro, and activation of B7-1 in cultured podocytes led to reorganization of vital slit diaphragm proteins. In summary, upregulation of B7-1 in podocytes may contribute to the pathogenesis of proteinuria by disrupting the glomerular filter and provides a novel molecular target to tackle proteinuric kidney diseases. Our findings suggest a novel function for B7-1 in danger signaling by nonimmune cells.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                nefrologia
                Nefrología (Madrid)
                Nefrología (Madr.)
                Sociedad Española de Nefrología (Cantabria, Santander, Spain )
                0211-6995
                1989-2284
                2012
                : 32
                : 5
                : 558-572
                Affiliations
                [02] Barcelona orgnameHospital Universitari Vall d'Hebron orgdiv1Servicio de Bioquímica
                [01] Barcelona orgnameHospital Universitari Vall d'Hebron orgdiv1Servicio de Nefrología
                [03] Barcelona orgnameHospital Universitari Vall d'Hebron orgdiv1Unidad de Investigación, Cirugía General
                Article
                S0211-69952012000700002
                10.3265/Nefrologia.pre2012.Jun.11396
                23013941
                8800dc37-ab20-41fc-a0b9-53ab0cce97e2

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 11 June 2012
                : 20 April 2012
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 130, Pages: 15
                Product

                SciELO Spain


                N-acetyl-glucosaminidase,Interleukin 13,Biomarcadores,Síndrome nefrótico,CD80 urinario,Hemopexina,Receptor soluble IL-2,Receptor soluble uroquinasa,Anticuerpos anti receptor tipo M de la fosfolipasa,Beta-2 microglobulina,N-acetil-glucosaminidasa,Interleuquina 13,Biomarkers,Nephrotic syndrome,Urinary CD80,Hemopexyn,Soluble IL-2 receptor,Urokinase soluble receptor,Anti PLRA2 antibodies,Beta 2 microglobulin

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