Suchergebnisse

Chronic kidney disease (CKD) is a prevalent cause of morbidity and mortality worldwide. A hallmark of CKD progression is renal fibrosis characterized by excessive accumulation of extracelular matrix (ECM) proteins. In this study, we aimed to investigate the correlation of the es_ESurinary proteome classifier CKD273 and individual urinary peptides with the degree of fibrosis. In total, 42 kidney biopsies and urine samples were examined. The percentage of fibrosis per total tissue area was assessed in Masson trichrome stained kidney tissues. The urinary proteome was analysed by capillary electrophoresis coupled to mass spectrometry. CKD273 displayed a significant and positive correlation with the degree of fibrosis (Rho = 0.430, P = 0.0044), while the routinely used parameters (glomerular filtration rate, urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio) did not (Rho = −0.222; −0.137; −0.070 and P = 0.16; 0.39; 0.66, respectively). We identified seven fibrosis-associated peptides displaying a significant and negative correlation with the degree of fibrosis. All peptides were collagen fragments, suggesting that these may be causally related to the observed accumulation of ECM in the kidneys. CKD273 and specific peptides are significantly associated with kidney fibrosis; such an association could not be detected by other biomarkers for CKD. These non-invasive fibrosis-related biomarkers can potentially be implemented in future trials ; The research presented in this manuscript was supported in part by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement No. 642937 (RENALTRACT; MSCA-ITN-2014-642937) and by the "Clinical and system-omics for the identification of the Molecular Determinants of established Chronic Kidney Disease" (iMode-CKD, PEOPLE-ITN-GA-2013-608332). AO was supported by Intensificacion ISCIII and RETIC REDINREN RD016/0009 FEDER funds; MDSN was supported by Miguel Servet program

The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving < 50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis(i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. the diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification. ; Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1006 AZ Amsterdam, Netherlands ; Columbia Univ, Coll Phys & Surg, New York, NY USA ; Rush Med Coll, Chicago, IL 60612 USA ; Cornell Univ, Weill Med Coll, New York, NY USA ; Univ Washington, Seattle, WA 98195 USA ; Columbia Presbyterian Med Ctr, New York, NY 10032 USA ; NIH, Bethesda, MD 20892 USA ; Leiden Univ, Med Ctr, Leiden, Netherlands ; Imperial Coll Med Sch, London, England ; San Carlo Borromeo Hosp, Milan, Italy ; Vanderbilt Univ, Nashville, TN USA ; SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA ; Ohio State Univ, Columbus, OH 43210 USA ; Georges Pompidou European Hosp, Paris, France ; St Vincents Hosp, Fitzroy, Vic 3065, Australia ; Univ N Carolina, Sch Med, Chapel Hill, NC USA ; Univ Kebangsaan Malaysia, Kuala Lumpur, Malaysia ; Hop Necker Enfants Malad, Paris, France ; Univ Malaya, Sch Med, Kuala Lumpur, Malaysia ; Okayama Univ, Grad Sch Med & Dent, Okayama, Japan ; Universidade Federal de São Paulo, São Paulo, Brazil ; Univ Tsukuba, Ibaraki, Japan ; Universidade Federal de São Paulo, São Paulo, Brazil ; Web of Science