This prospective study was designed to evaluate the eventual correction of anemia and iron status in 39 iron-deficient uremics starting hemodialysis. Nine patients (control group) had no iron supplementation, 10 had oral ferrous iron, and 20 were treated with intravenous iron gluconate. Follow-up periods were 12 months for the control group and 26 months for patients treated with oral or intravenous iron. No patient was treated with erythropoietin. At zero time, all patients were anemic (Hb <78 g/l) and showed signs of severe iron deficiency, diagnosed on the basis of depleted bone marrow iron stores, reduced hemoglobin iron, and transferrin saturation <21%. The hemoglobin levels, observed in patients of the control and the oral iron groups at the end of the follow-up periods, were not significantly different from those detected at zero time. In contradistinction, patients treated with intravenous iron showed after 26 months of follow-up a significant increase of blood hemoglobin values, reaching a mean value of 126 g/l. So far, this evidence supports both the concept that iron absorption is compromised in chronic uremics and that the parenteral way is the more effective route for iron replacement in this specific group of patients.

Solutions for peritoneal dialysis (PD), the hyperosmolarity of which is obtained with glucose, have been shown to initiate and maintain a situation of continuous mesothelial cell injury associated with a process of regeneration which also takes place continuously. The present study was done using the in vivo and almost in situ technique of mesothelial cell imprints. Acute exposure to 4.25% glucose solution at pH 5.2 and 7.0 induced higher mitotic activity, defective cytokinesis, and reduced cell viability. Long-term exposure (15 and 30 days) to both 4.25% glucose solutions was associated with a reduced population density, increased surface area, and lower mesothelial cell viability, regardless of the pH. The use of 1.5% glucose fluid showed that this effect was dose related. After 30 days of recovery, mesothelial cells exposed to the high-glucose solution at both pH 5.2 and 7.0 appeared repopulated by small cells and showed evidence of defective cytokinesis. So far, it appears that the alterations observed after long-term exposure of the mesothelium to PD fluid are mainly caused by the high concentration of glucose per se. The additional effects of hyperosmolarity are still unclear, whereas the eventual role of low pH, at least in the experimental model used here, can be defined as less than marginal.

Previous studies, done using our mouse model for population analysis of the mesothelium, showed evidence indicating that in vivo, long-term exposure (up to 30 days) of the peritoneum to high-glucose (4.25% D-glucose) concentration dialysis solutions resulted in a hypertrophic mesothelial phenotype characterized by increased cell surface area, multinucleation, low proliferative capabilities, reduced cell viability, and enhanced enzymatic activity. These elements that define a senescent population of cells were not related to the pH of the fluid and its osmolality, or to the presence of buffer lactate. The present study was designed to explore the adverse effects of a lactate-free, filter-sterilized, high-D-glucose concentration solution (4.25%) at normal pH and prepared in Hanks’ buffered salt solution after 2 h, 15 and 30 days of once a day intraperitoneal injection. Analysis of our observations indicate that in vivo exposure of the mesothelium to a high-glucose concentration induced a decreased density of the cell population, made up by larger and multinucleated cells, the viability of which was significantly lower than that observed in intact unexposed mice. The prevalence of mitosis showed an early and short-lived acceleration (up to 3 days), followed by values near zero during the rest of the follow-up period. So far, the main effect of the high-glucose concentration appears to result not from a mechanism of cytotoxicity, but from a substantial change in the life cycle of the exposed cell population, leading to their premature senescence and death in apoptosis. We hypothesize that this outcome may well be mediated by sustained oxidative stress derived from both a reduced production of scavengers, as well as the increased generation of oxygen-reactive species.

No abstract

We examined under the electron microscope samples of parietal peritoneum obtained from nine nondiabetic chronic uremics -six of them on maintenance intermittent peritoneal dialysis, ranging in age from 52 to 82 years -mean 64.4 ± 8.1 years and of nine non-uremic, non-diabetic patients -mean age 40.7 ± 12.2 years. Postcapillary venules and small venules showed areas with several layers of reduplicated basal lamina. Some microvessels showed gaps in basallamina with and/or without focal reduplication. Reduplicated submesothelial basal lamina was found in only one patient. These changes were not observed in the nine non-uremic, non-diabetic controls. To the best of our knowledge, this is the first description in humans of such alterations in the aforementioned locations, which may well be secondary to aging and/or to the intense mesothelial renewal observed in I.P.D. patients. We need to determine the possible influence of these ultrastructural changes on transperitoneal transfer of water and solutes during peritoneal dialysis. The basal lamina of blood vessels may not be of uniform thickness. Human non-diabetic adults show significant increase in capillary basal lamina thickness as one moves from head to foot (1). Those regional variations may be related to differences in venous hydrostatic pressure effective on the capillary bed (1). This paper decribes the first observations of reduplicated basal lamina of microvessels in the parietal peritoneum and of that subjacent to mesothelial cells in elderly, non-diabetic uremic patients.