1. Fascin-1 is released from proximal tubular cells in response to calcineurin inhibitors (CNIs) and correlates with isometric vacuolization in kidney transplanted patients
- Author
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Jacobs-Cachá C, Ib, Torres, Joan Lopez Hellin, Cantarell C, Ma, Azancot, Román A, Moreso F, Serón D, Meseguer A, Sarró E, Institut Català de la Salut, [Jacobs-Cachá] Grup en Fisiopatologia Renal, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [Torres IB] Servei de Nefrologia, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [López-Hellín J] Grup en Fisiopatologia Renal, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [Cantarell C, Azancot MA] Servei de Nefrologia, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Román A] Servei de Neumologia, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Moreso F, Serón D] Servei de Nefrologia, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Meseguer A]Grup en Fisiopatologia Renal, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Department of Biochemistry and Molecular Biology, Faculty of Medicine, Autonomous University of Barcelona, Bellaterra (Barcelona), Spain. [Sarró E]Grup en Fisiopatologia Renal, Vall d’Hebron Institut de Recerca, Barcelona, Spain., and Vall d'Hebron Barcelona Hospital Campus
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Ronyons - Trasplantació ,Nefrotoxicologia ,Marcadors bioquímics ,acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de calcineurina [COMPUESTOS QUÍMICOS Y DROGAS] ,intervenciones quirúrgicas::trasplante::trasplante de órganos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Calcineurin Inhibitors [CHEMICALS AND DRUGS] ,Original Article ,Surgical Procedures, Operative::Transplantation::Organ Transplantation [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] ,Biological Factors::Biomarkers [CHEMICALS AND DRUGS] ,factores biológicos::biomarcadores [COMPUESTOS QUÍMICOS Y DROGAS] - Abstract
Fascin-1; Nephrotoxicity; Transplant Fascina-1; Nefrotoxicitat; Trasplantament Fascina-1; Nefrotoxicidad; Trasplante Immunosuppression based on calcineurin inhibitors (CNIs) has greatly improved organ transplantation, although subsequent nephrotoxicity significantly hinders treatment success. There are no currently available specific soluble biomarkers for CNI-induced nephrotoxicity and diagnosis relies on renal biopsy, which is costly, invasive and may cause complications. Accordingly, identification of non-invasive biomarkers distinguishing CNI-induced kidney tubular damage from that of other etiologies would greatly improve diagnosis and enable more precise dosage adjustment. For this purpose, HK-2 cells, widely used to model human proximal tubule, were treated with CNIs cyclosporine-A and FK506, or staurosporine as a calcineurin-independent toxic compound, and secretomes of each treatment were analyzed by proteomic means. Among the differentially secreted proteins identified, only fascin-1 was specifically released by both CNIs but not by staurosporine. To validate fascin-1 as a biomarker of CNI-induced tubular toxicity, fascin-1 levels were analyzed in serum and urine from kidney-transplanted patients under CNIs treatment presenting or not isometric vacuolization (IV), which nowadays represents the main histological hallmark of CNI-induced tubular damage. Patients with chronic kidney disease (CKD) and healthy volunteers were used as controls. Our results show that urinary fascin-1 was only significantly elevated in the subset of CNI-treated patients presenting IV. Moreover, fascin-1 anticipated the rise of sCr levels in serially collected urine samples from CNI-treated pulmonary-transplanted patients, where a decline in kidney function and serum creatinine (sCr) elevation was mainly attributed to CNIs treatment. In conclusion, our results point towards fascin-1 as a putative soluble biomarker of CNI-induced damage in the kidney tubular compartment.