Type 1 diabetes generally results from autoimmune destruction of pancreatic islet ␤-cells, with consequent absolute insulin deficiency and complete dependence on exogenous insulin treatment. The relative paucity of donations for pancreas or islet allograft transplantation has prompted the search for alternative sources for ␤-cell replacement therapy. In the current study, we used pluripotent undifferentiated human embryonic stem (hES) cells as a model system for lineage-specific differentiation. Using hES cells in both adherent and suspension culture conditions, we observed spontaneous in vitro differentiation that included the generation of cells with characteristics of insulin-producing ␤-cells. Immunohistochemical staining for insulin was observed in a surprisingly high percentage of cells. Secretion of insulin into the medium was observed in a differentiation-dependent manner and was associated with the appearance of other ␤-cell markers. These findings validate the hES cell model system as a potential basis for enrichment of human ␤-cells or their precursors, as a possible future source for cell replacement therapy in diabetes.

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Podocyte and glomerular research is center stage for the development of improved preventive and therapeutic strategies for chronic progressive kidney diseases. Held April 3-6, 2016, the 11th International Podocyte Conference took place in Haifa and Jerusalem, Israel, where participants from all over the world presented their work on new developments in podocyte research. In this review, we briefly highlight the advances made in characterizing the mechanisms involved in podocyte development, metabolism, acquired injury, and repair, including progress in determining the roles of genetic variants and microRNA in particular, as well as the advances made in diagnostic techniques and therapeutics.

are not yet fully clarified, it is well accepted that nephrin and podocin are involved in the development of proteinuria. The effects of early treatment with various antiproteinuric therapies on proteinuria and glomerular staining of nephrin and podocin in rats with experimental NS have not been previously studied. Proteinuria and glomerular nephrin and podocin immunofluorescence were examined in rat kidneys with adriamycin-induced NS and the effects of antiproteinuric drug therapies during 5 wk with enalapril, losartan, alone or in combination, omapatrilat, and mycophenolate mofetil on these parameters were assessed. Injection of adriamycin caused a significant increase in daily (from 21.8 Ϯ 1.4 to 983.1 Ϯ 45.8 mg/day, P Ͻ 0.01) and cumulative protein excretion (from negligible values to 22,490 Ϯ 931 mg, P Ͻ 0.001) during 5 wk. Early treatment with enalapril significantly decreased the daily (641.7 Ϯ 82.4 mg/day, P Ͻ 0.0023) and cumulative proteinuria (15,727 Ϯ 2,204 mg, P Ͻ 0.001). A similar effect, although to a lesser extent, was obtained after omapatrilat treatment: cumulative proteinuria was reduced to 18,706 Ϯ 1,042 mg, P Ͻ 0.001. In contrast, losartan treatment did not significantly influence the cumulative proteinuria that remained comparable (20,351 Ϯ 1,360 mg, P Ͼ 0.05) to that observed in untreated NS rats. Unexpectedly, when losartan was given in combination with enalapril, it abolished the beneficial effects of the latter. Pretreatment with mycophenolate mofetil exerted a moderate antiproteinuric effect, which appeared only during the last week of the experimental treatment. Nephrotic rats exhibited severe disruption of slit diaphragm structure as seen by rapid and profound loss of nephrin and podocin. Beneficial effects of enalapril, omapatrilat, and mycophenolate mofetil paralleled the preservation of nephrin, as determined immunohistochemically, and enabled prediction of significant antiproteinuric responses. Enalapril alone or in combination with losartan resulted in significant preservation of podocin. Pretreatment with enalapril, and to a lesser extent omapatrilat, is superior to losartan in reducing proteinuria in NS rats. A combination of ACE inhibitors with ANG II receptor blockers does not provide any advantageous antiproteinuric therapy in these animals. Nephrin loss is an indication of proteinuria in NS and the antiproteinuric effects of ACE inhibitors, vasopeptidase inhibitors, and mycophenolate mofetil attenuate this reduction. Not all the drugs which restore podocin reduce urinary protein in NS.adriamycin; proteinuria ADRIAMYCIN (ADR)-induced nephrotic syndrome (NS) in the rat is characterized by massive proteinuria, hypoalbuminemia, dyslipidemia, hypercoagulability, edema, and ascites formation (5,16,25,26). The common denominator of this experimental nephropathy, which mimics minimal change disease and various primary and secondary kidney diseases such as diabetic nephropathy, systemic lupus erythematosus and others, is glomerular dysfunction resulting in a massive proteinuria (8)....

The breath pattern of the ESRD patients approached the healthy pattern during the HD treatment, without reaching it completely. Gas chromatography/mass spectrometry identified four volatile organic compounds as potential ESRD biomarkers. Although this pilot study has yielded encouraging results, additional large-scale clinical studies are required to develop a fast, noninvasive breath test for monitoring HD adequacy in real time.

BackgroundHeparanase, an endoglycosidase that cleaves heparan sulfate (HS), is involved in various biologic processes. Recently, an association between heparanase and glomerular injury was suggested. The present study examines the involvement of heparanase in the pathogenesis of Adriamycin-induced nephrotic syndrome (ADR-NS) in a mouse model.MethodsBALB/c wild-type (wt) mice and heparanase overexpressing transgenic mice (hpa-TG) were tail-vein injected with either Adriamycin (ADR, 10 mg/kg) or vehicle. Albuminuria was investigated at days 0, 7, and 14 thereafter. Mice were sacrificed at day 15, and kidneys were harvested for various analyses: structure and ultrastructure alterations, podocyte proteins expression, and heparanase enzymatic activity.ResultsADR-injected wt mice developed severe albuminuria, while ADR-hpa-TG mice showed only a mild elevation in urinary albumin excretion. In parallel, light microscopy of stained cross sections of kidneys from ADR-injected wt mice, but not hpa-TG mice, showed mild to severe glomerular and tubular damage. Western blot and immunofluorescence analyses revealed significant reduction in nephrin and podocin protein expression in ADR-wt mice, but not in ADR-hpa-TG mice. These results were substantiated by electron-microscopy findings showing massive foot process effacement in injected ADR-wt mice, in contrast to largely preserved integrity of podocyte architecture in ADR-hpa-TG mice.ConclusionsOur results suggest that heparanase may play a nephroprotective role in ADR-NS, most likely independently of HS degradation. Moreover, hpa-TG mice comprise an invaluable in vivo platform to investigate the interplay between heparanase and glomerular injury.

Natriuretic peptides are an important endocrine system in the regulation of body fluid balance and blood pressure. Corin mediates an essential step in the cascade of natriuretic peptide biosynthesis and eventually their action. Thus, it is postulated that aberrations in the normal activity of corin may contribute to cardiovascular and renal diseases.

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