Suchergebnisse

Publisher's version (útgefin grein) ; Rationale & Objective: Glomerular filtration rate (GFR) estimation based on creatinine or cystatin C level is currently the standard method for assessing GFR in epidemiologic research and clinical trials despite several important and well-known limitations. Plasma iohexol clearance has been proposed as an inexpensive method for measuring GFR that could replace estimated GFR in many research projects. However, lack of standardization for iohexol assays and the use of different protocols such as single- and multiple-sample methods could potentially hamper comparisons across studies. We compared iohexol assays and GFR measurement protocols in 3 population-based European cohorts. Study Design: Cross-sectional investigation. Setting & Participants: Participants in the Age, Gene/Environment Susceptibility-Kidney Study (AGES-Kidney; n = 805), the Berlin Initiative Study (BIS, n = 570), and the Renal Iohexol Clearance Survey Follow-up Study (RENIS-FU; n = 1,324). Tests Compared: High-performance liquid chromatography analyses of iohexol. Plasma iohexol clearance calculated using single- versus multiple-sample protocols. Outcomes: Measures of agreement between methods. Results: Frozen samples from the 3 studies were obtained and iohexol concentrations were remeasured in the laboratory at the University Hospital of North Norway. Lin's concordance correlation coefficient ρ was >0.96 and Cb (accuracy) was >0.99 for remeasured versus original serum iohexol concentrations in all 3 cohorts, and Passing-Bablok regression did not find differences between measurements, except for a slope of 1.025 (95% CI, 1.006-1.046) for the log-transformed AGES-Kidney measurements. The multiple-sample iohexol clearance measurements in AGES-Kidney and BIS were compared with single-sample GFRs derived from the same iohexol measurements. Mean bias for multiple-sample relative to single-sample GFRs in AGES-Kidney and BIS were −0.25 and −0.15 mL/min, and 99% and 97% of absolute differences were within 10% of the multiple-sample result, respectively. Limitations: Lack of comparison with an independent gold-standard method. Conclusions: Agreement between the iohexol assays and clearance protocols in the 3 investigated cohorts was substantial. Our findings indicate that plasma iohexol clearance measurements can be compared across these studies. ; AGES-Kidney was supported by a grant from National Institutes of Health, United States (R01 DK082447), a contract from the National Institute on Aging, United States (N01-AG-1-2100), Hjartavernd, Iceland (Icelandic Heart Association), and the Icelandic Parliament (Althingi). The Icelandic Heart Association provided support for data collection. BIS measurements were funded by the KfH-Foundation of Preventive Medicine, Germany and the Dr. Werner Jackstädt Foundation, Germany. RENIS-FU was funded by the Northern Norway Regional Health Authority and supported by a grant from Boehringer-Ingelheim, Germany. The funding sources did not have any role in study design, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. ; Peer Reviewed

Los nombres de dos de los autores son incorrectos. Los nombres del noveno y décimo autor son respectivamente: Alberto Ortíz y María Dolores Sánchez-Niño. La abreviatura correcta en contribuciones del décimo autor es MDSN. La corrección se publicó en: PLoS ONE 8(8): 10.1371/annotation/0c4c8143-c10e-4fe0-b944-b1fcd79995e7. ; The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U) from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N = 6) were sufficient to induce angiogenic and proliferative effects (1.3460.26 nmol L-1). In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor. ; This study was supported by a grant from the German Research Foundation (DFG, Ja-972/11-1; JJ), the Sonnenfeld Foundation (JJ; VJ) and Federal Ministry of Education and Research (BMBF; 01GR0807 (JJ)). The author (VJ; JJ) was supported by grants FP7-HEALTH24 2009-2.4.5-2 to "SYSKID" (241544) and "HEALTH 2011.2.4.2-2″ to "Mascara" (278249) from the European Union. Eutox, FIS PS09/00447, ISCIII-RETIC REDinREN/RD12/0021/0001 and 0004. Comunidad de Madrid/S2010/BMD-2378(NMDS; AAO); FIS-Sara Borrell to MDSN, Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) (AAO). VJ received a grant from the Else-Kroener-foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.