OBJECTIVE -Patients with diabetes commonly have a greater degree of anemia for their level of renal impairment than those presenting with other causes of renal failure. To clarify the contribution and differing roles of diabetes and nephropathy in the development of anemia in diabetic patients, we examined the hematologic and hematinic parameters of diabetic patients without nephropathy.RESEARCH DESIGN AND METHODS -The study group was comprised of 62 patients with type 2 diabetes who had been followed for a median of 7 years. For the study, these patients had additional samples taken during their annual routine blood testing for the measurement of extra parameters, including serum ferritin, serum erythropoietin (Epo) levels, and the percentage of reticulocytes. These measurements were combined with the routine parameters Hb, hematocrit, HbA 1c , and glomerular filtration rate.RESULTS -In all, 8 of the 45 male patients (17.8%) and 2 of the 17 female patients (11.8%) were classified as anemic (Hb Ͻ13g/dl and Ͻ11.5g/dl, respectively). Although only a small number of the patients had anemia as defined by normal values, a retrospective analysis of individual patients over time revealed a sustained though small decrease in Hb from initial presentation. A statistically significant difference in Epo levels (P ϭ 0.016 by Kruskal-Wallis test) was observed from the group with the lowest (Hb Յ11.5) to that with the highest (Hb Ն14.5) Hb values, with a median Epo value of 37 (interquartile range 24 -42) vs. 13 (9 -15) IU/l, respectively. In contrast, there was no evidence of an increased reticulocyte response to higher levels of Epo (r ϭ 0.134 [Pearsons], P ϭ 0.36). Reticulocyte counts ranged from 44 (38 -57) to 76.5 (56 -83) in the lowest and highest Hb groups, respectively.CONCLUSIONS -Although only a small number of subjects in the group were overtly anemic, all subjects had an ongoing, small but significant decrease in Hb since presentation. This study of diabetic patients without nephropathy shows an expected increase in Epo production in response to lowering levels of Hb but without the expected reticulocyte response. Diabetes Care 28:1118 -1123, 2005I n the U.K., as in the rest of the Western world, diabetes is the most prevalent cause of renal failure. Over the next 10 years, the number of patients with diabetes and end-stage renal disease is expected to double, causing a significant increase in the burden of care for this patient population (1). Although the prognosis with diabetic nephropathy has improved since early reports (2,3), there remains an excess mortality of 70 -100 times that of an otherwise matched population (4). Survival rates on dialysis remain poor, with up to 33% of patients dying within a year of starting dialysis (4). Furthermore, for patients who require renal replacement therapy, morbidity as assessed by hospitalization is 2-3 times greater than for nondiabetic patients with end-stage renal failure (2). This excess of morbidity and mortality in part relates to the high incidence of cardiovascul...

Our data demonstrate that long-standing type II diabetes alone is not sufficient to induce progressive nephropathy unless secondary injurious mechanisms such as hypertension are present. The hypertensive GK rat provides a novel model to investigate the mechanisms involved in diabetic nephropathy.

CA-AKI carries significant implications in terms of both development of progressive renal disease and high long-term patient mortality.

Anecdotal evidence suggests that high fibre supplementation of dietary intake may have health benefits in renal disease related to alterations in circulating levels of short-chain fatty acids. The aim of the study was to examine the hypothesis that dietary manipulation may increase serum butyrate and thus have potential beneficial effects in renal disease. We examined the effect of dietary supplementation with a gum arabic sample of standardized molecular characteristics, Acacia(sen) SUPERGUM EM2 (SUPERGUM), on systemic levels of butyrate in normal human subjects. In an in vitro study, we also examined the potential role of butyrate in modifying the generation of the profibrotic cytokine transforming growth factor-beta (TGF-beta1) by renal epithelial cells. Following 8 weeks of dietary supplementation with 25 g/day of SUPERGUM, there was a two-fold increase in serum butyrate (n=7, P=0.03). In vitro work demonstrated that exposure of renal epithelial cells to elevated concentrations of butyrate suppressed both basal and stimulated TGF-beta1 synthesis. The action of butyrate was mediated by suppression of the extracellular signal-regulated kinase/mitogen-activated protein kinase signalling pathway. In addition, butyrate exposures reduced the response of renal epithelial cells to TGF-beta1 as assessed by luciferase activity of a TGF-beta-responsive reporter construct. Attenuation of TGF-beta1 signalling was associated with reduced phosphorylation of Smad 3 and decreased trafficking of TGF-beta1 receptors into signalling, non-lipid raft-associated membrane fractions. In conclusion, the data demonstrate that dietary supplementation with SUPERGU increased serum butyrate, which at least in vitro has beneficial effects on renal pro-fibrotic cytokine generation.

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Background Haemodialysis patients receive very little involvement in their end-of-life care decisions. Issues relating to death and dying are commonly avoided until late in their illness. This study aimed to explore the experiences and perceptions of doctors and nurses in nephrology for involving haemodialysis patients in end-of-life care decisions.

Mesangial cell apoptosis occurs in experimental diabetic nephropathy, and this correlates with worsening albuminuria. This study examines the mechanism by which glucose modulates mesangial cell apoptosis. Apoptosis was induced in mesangial cells by serum deprivation in the presence of 5 or 25 mM D-glucose, and examined by expression of Annexin-V and disruption of mitochondrial transmembrane potential. Involvement of Bax, Bcl-2 and NF-jB were examined by RT-PCR and EMSA. Involvement of TGF-b1 was sought by determining the effect of recombinant TGF-b1on apoptosis and the mediators of the apoptotic pathway (Bcl2/ Bax and NF-jB). Culture of cells in the presence of 25 mM D-glucose (i) enhanced apoptosis stimulated by serum depletion, (ii) enhanced activation of caspase-3, (iii) inhibited NF-jB activation, and (iv) decreased Bcl-2:Bax ratio. Inhibition of NF-jB using SN50, also increased mesangial cell apoptosis, and decreased Bcl-2:Bax ratio. Addition of TGF-b1 to mesangial cells mimicked the effect of high glucose reducing NF-jB expression and Bcl-2:Bax ratio. Furthermore glucose-mediated enhanced apoptosis was inhibited by the addition of a blocking antibody to TGF-b1. Exposure of mesangial cells to 25 mM D-glucose stimulated the generation of both total and active TGF-b1 in the cell culture supernatant, this increase was only significant after 48-72 h, that is at a time point later than enhanced apoptosis. Addition of 25 mM D-glucose, however, increased sensitivity of mesangial cells to TGF-b1 as assessed by luciferase activity of a Smad sensitive reporter construct. The data suggest that elevated glucose concentration enhanced the pathway leading to apoptosis following serum deprivation. Furthermore, it is likely that this is dependent on glucose-mediated enhanced sensitivity to endogenous TGF-b1 rather than glucose stimulated de novo TGF-b1 synthesis.

BackgroundMedical curricula are increasingly using small group learning and less didactic lecture-based teaching. This creates new challenges and opportunities in how students are best supported with information technology. We explored how university-supported and external social media could support collaborative small group working on our new undergraduate medical curriculum.MethodsWe made available a curation platform (Scoop.it) and a wiki within our virtual learning environment as part of year 1 Case-Based Learning, and did not discourage the use of other tools such as Facebook. We undertook student surveys to capture perceptions of the tools and information on how they were used, and employed software user metrics to explore the extent to which they were used during the year.ResultsStudent groups developed a preferred way of working early in the course. Most groups used Facebook to facilitate communication within the group, and to host documents and notes. There were more barriers to using the wiki and curation platform, although some groups did make extensive use of them. Staff engagement was variable, with some tutors reviewing the content posted on the wiki and curation platform in face-to-face sessions, but not outside these times. A small number of staff posted resources and reviewed student posts on the curation platform.ConclusionsOptimum use of these tools depends on sufficient training of both staff and students, and an opportunity to practice using them, with ongoing support. The platforms can all support collaborative learning, and may help develop digital literacy, critical appraisal skills, and awareness of wider health issues in society.