RESUMEN
The projected future demand for renal replacement therapies for patients with end-stage renal failure requires preparedness at different levels. The deliberations focus predominantly on the disproportionately high financial burden of care for patients on routine dialysis therapy compared with other chronic conditions. However, even today there are concerns regarding the shortage of healthcare workers in the field of nephrology. A substantial increase in trained healthcare professionals is needed for the future delivery and care of patients requiring haemodialysis (HD) that 89% of patients on dialysis receive; a sustainable health workforce is the cornerstone of any healthcare system. The multimorbid nature of chronic kidney disease as well as the complexity-especially the technical aspects-of HD are deterrents for pursuing nephrology as a career. An educational platform that critically examines the essential issues and components of HD therapy was thus considered appropriate to create or renew interest in nephrology. By providing broader and newer perspectives of some of the core principles around which HD evolves, with this set of articles we seek to facilitate a better appreciation of HD. We believe that such a reappraisal of either poorly understood or ill-defined principles, including usage of terminology that is imprecise, will help facilitate a better understanding of the functioning principles of HD.
RESUMEN
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 (1.34 ± 0.26 nmol L(-1)). In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor.