Abstract. Although iron sucrose and iron gluconate are generally well tolerated in patients who are treated for renal anemia, recent clinical studies and cell culture experiments suggested significant toxicity and long-term side effects arising from the use of these iron complexes. Because of the possible role of iron in infection or cardiovascular disease, it was theorized that parenteral iron compounds influence endothelial and PMN interaction in vitro. A well-established double-chamber method was used to assess the effect of different concentrations of iron sucrose and iron gluconate (1, 25, 50, and 100 g/ml) on the transendothelial migration of PMN. Preincubation of PMN and endothelial cells as well as preincubation of PMN alone with 25, 50, or 100 g/ml iron resulted in a significant decrease in PMN migration. In contrast, after incubation of the endothelial cells alone with iron, no reduction in the transendothelial migration of PMN was observed. Preincubation of PMN and/or endothelial cells with 1 g/ml iron did not lead to any decrease in the rate of migrated PMN. The only significant change in experiments with 1 g/ml was an increase in PMN migration after preincubation of endothelial cells and PMN with iron gluconate. A four-way ANOVA showed a significant effect of the iron concentration (P Ͻ 0.000001), of type of iron complex (P Ͻ 0.005), of the preincubation of endothelial cell (P Ͻ 0.001), and of the preincubation of PMN with iron (P Ͻ 0.000001) on PMN diapedesis. It is concluded that iron sucrose and iron gluconate cause a significant inhibition of transendothelial migration of PMN.Renal anemia therapy requires an intravenous iron substitution in addition to the erythropoietin therapy in the majority of patients (1). Iron substitution not only reduces the erythropoietin dosage needed but also is necessary to maintain the target hemoglobin above 11 g/dl (2,3). There are several iron preparations for intravenous use available, all of which have potential side effects, such as allergic reactions, cell injury, or endothelial dysfunction (4 -7). Moreover, iron therapy may be associated with infectious complications and with loss of the ability of patient serum to resist the bacterial growth (8 -10). PMN play a vital role in the nonspecific immune reaction against bacterial infections executing functions such as chemotaxis, transendothelial migration, phagocytosis, and intracellular killing by proteolytic enzymes or toxic oxygen radicals. Although the effects of iron on chemotaxis of PMN, phagocytosis, and intracellular killing in PMN were studied previously, the effect of iron complexes on PMN-endothelial cell interaction is unknown. Therefore, we examined the effect of incubation of PMN and/or endothelial cells with two widely used iron complexes, iron(III)-hydroxide-sucrose complex (iron sucrose) and iron(III)-sodium-gluconate in sucrose (iron gluconate), on the PMN migration through the endothelium in an in vitro setting.

. A SAGEbased comparison between glomerular and aortic endothelial cells.

No abstract

Abstract. The effect of thiamine (vitamin B 1 ) or riboflavin (vitamin B 2 ) availability on fasting total homocysteine (tHcy) plasma levels in end-stage renal disease patients is unknown. A cross-sectional study was performed in a population of nonvitamin supplemented patients maintained on continuous ambulatory peritoneal dialysis. Red blood cell availability of thiamine (␣-ETK) and of riboflavin (␣-EGR), along with other predictors of tHcy plasma levels, was considered in the analysis. There was a linear association of ␣-EGR with tHcy plasma concentrations (P ϭ 0.009), which was not observed for ␣-ETK. Among red blood cell vitamins, ␣-EGR was the only predictor of tHcy levels (P ϭ 0.035), whereas ␣-ETK, red blood cell pyridoxal-5-phosphate supply (␣-EGOT) and red blood cell folate levels had no effect. The risk for having a high tHcy plasma levels within the fourth quartile (plasma tHcy Ͼ38.3 mol/L) was increased by an ␣-EGR Ͼ median (odds ratio, 4.706; 95% confidence interval, 1.124 to 19.704; P ϭ 0.026). By way of contrast, ␣-ETK had no effect in these analyses. Independent predictors of tHcy plasma levels were serum albumin, ␣-EGR, red blood cell folate, and certain MTHFR genotypes. A logistic regression analysis showed that the MTHFR genotype is a predictor for having a tHcy plasma concentration within the fourth quartile. In summary, riboflavin availability, as measured by ␣-EGR, is a determinant of fasting tHcy plasma levels in peritoneal dialysis patients. This finding may have implications for tHcy lowering therapy in individuals with end-stage renal disease.The majority of patients with impaired renal function present elevated total homocysteine (tHcy) plasma levels (1). Established predictors of tHcy plasma levels in the renal failure population include serum albumin and serum creatinine levels, creatinine clearance, folate status, vitamin B 12 and vitamin B 6 levels, as well as genetic variants in enzymes involved in the folate cycle or in the remethylation of homocysteine (2-7). An elevated tHcy plasma level can indicate folate and/or vitamin B 12 deficiency (8) and is associated with a variety of pathologic conditions such as vascular disease (9 -11) or birth defects (12). Although genetic and nongenetic factors have been shown to determine tHcy concentrations of patients with renal insufficiency, the cause of hyperhomocysteinemia among these patients is not completely understood (13).The role of B-group vitamins other than vitamin B 6 or vitamin B 12 as determinants of hyperhomocysteinemia in the general population and in the setting of renal insufficiency is far from clear, although vitamin B 1 (thiamine pyrophosphate) and vitamin B 2 (riboflavin) are involved in the metabolism of methionine and homocysteine.We assumed that thiamine or riboflavin availability is a predictor of fasting tHcy plasma levels in end-stage renal disease (ESRD). To test this hypothesis, we performed a crosssectional study among a population of non-vitamin supplemented patients maintained on continuous ambulatory perito...