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.

No abstract