Subcutaneous erythropoietin: a comparison of daily and thrice weekly administration.
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Biomedical subjects
Publications and source records attributed to M Pollok.
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Recombinant human erythropoietin (rHuEpo) is effective in correcting renal anemia with the development of hypertension as the most frequent side-effect. Compared to hemodialysis patients with normal hemoglobin concentration, nine examined patients with transfusion-dependent renal anemia had low blood pressure in the context of high alpha 2-receptor densities and high plasma levels of catecholamines. This constellation can be explained by a defective receptor-ligand-interaction. During treatment with rHuEpo all patients showed an increase in blood pressure due to increased peripheral resistance, accompanied by a significant fall in plasma noradrenaline and alpha 2-receptor-density. There was a significant negative correlation between hemoglobin concentration and alpha 2-receptor density. We conclude that correction of renal anemia abolishes anemia-mediated disturbance of alpha 2-receptor function with the consequence of receptor down-regulation and increased vasoconstriction, which contributes to the rise in arterial blood pressure.
The interdependence of blunted T cell proliferation induced by anti-CD3 monoclonal antibodies (mAb) and the preactivation of T lymphocytes (CD25+) in ESRD patients was investigated in this study. We focused on the density of IL-2 (CD25) receptors [IL-2R] on the lymphocyte surface rather than enumeration of IL-2R positive cells. The effect of exogenous IL-2 on these parameters was also tested. Blunted T lymphocyte proliferation induced by anti-CD3 mAb is only partially corrected by addition of exogenous IL-2 after 24 hrs. Freshly isolated uremic CD4 T cells show higher percentage of IL-2 positive cells and a higher IL-2R density on the cell surface compared to controls. However, after anti-CD3 mAb stimulation the number of IL-2R positive cells and IL-2R density in CD4 T subset was significantly lower than in samples from normal donors. Exogenous IL-2 had no influence on IL-2R expression on CD4 cells in uremic patients. On the other hand, following anti-CD3 mAb stimulation uremic CD8 cells reveal more IL-2R positive cells with higher IL-2R density than in controls. Moreover, exogenous IL-2 enhance IL-2R expression and density on uremic CD8 cells more than in controls. Our results suggest that the blunted T cell proliferation in ESRD patients might result from (a) preactivation of CD4 T cells, (b) diminished response of uremic CD4 T cells to IL-2, and (c) higher suppressor cells activity.
TCR/CD3 receptor complex plays a central role in antigen recognition and T cell activation. Therefore, the present study investigates TCR alpha/beta (TCR-1) and CD3 receptor density (RD, number of receptors per cell) on uremic CD4 T lymphocytes in relation to T cell proliferative response induced by anti-CD3 monoclonal antibodies (mAb). The influence of uremic serum on TCR/CD3 receptor expression of normal and uremic CD4 T lymphocytes was evaluated as well. We found, that: a) percentage of TCR-1 and CD3 positive cells of freshly isolated CD4 T lymphocytes is the same in controls and ESRD-patients, but the TCR/CD3 RD is lower on uremic CD4 T lymphocytes, b) Incubation for 24 h with uremic serum lowers TCR/CD3 RD on normal and uremic CD4 T cells, c) There is positive correlation between TCR/CD3 RD and anti-CD3 induced lymphocyte proliferation. These data might also support the hypothesis that blunted T-cell response to antigen in uremia is due to down-regulation of the TCR/CD3 receptor complex by uremic milieu.
Recombinant human erythropoietin (EPO) has been used for 4 years in end-stage renal disease patients, administered intravenously 3 times a week. A study was undertaken to determine the optimal way of administration comparing 3 times weekly intravenous EPO to self-administered daily subcutaneous EPO (SADSCEPO). In a first group of 4 patients, we demonstrated that the change from 3 times weekly intravenous EPO to SADSCEPO permitted a dose reduction of 70%. In a second group of 20 patients who started the EPO therapy with the daily subcutaneous route at a median dose of 12 U/kg/day, the hematocrit increased from 20 to 30% in 4 months and remained over 30% in spite of a median dose reduction to 9 U/kg/day. The patients' acceptance of SADSCEPO was good. The mechanism allowing such a dose reduction is unknown. However, the significant reduction in median dosage requirement with the subcutaneous route should allow a greater number of patients to be treated more cost-effectively.
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Treatment of renal anemia with rhEPO (120 U/kg body weight/hemodialysis) in transfusion-dependent patients on maintenance hemodialysis led to an increase in blood pressure, regional peripheral resistance and whole blood viscosity. Our results are in agreement with earlier findings that partial correction of renal anemia results in hemodynamic changes characterized by a fall in cardiac output together with an increase in blood pressure due to increased vascular resistance. The increase in whole blood viscosity correlated with the increase in regional peripheral resistance but not with the increase in mean arterial blood pressure. Thus, other regulating factors of vascular resistance must be involved. Correction of renal anemia does not influence the reninangiotensin system. However, peripheral responsiveness of vascular smooth muscles may have changed due to improved tissue oxygenation and thus leading to an increase in vasoconstriction.
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Plasma and ultrafiltrate beta-2-microglobulin (B2M) concentrations were determined during hemofiltration (HF) and hemodialysis (HD) in order to evaluate elimination kinetics of B2M. Calculations were done on the basis of plasma-water-concentrations (PWC). Elimination of B2M during HF follows first order kinetics (r = 0.97) and the volume of B2M distribution was calculated to be 17 +/- 2% of body weight. This reflects extracellular volume (ECV). Changes of ECV in HD were induced by weight loss and further provoked by fluid shifts from intra- to extracellular volume and vice versa induced by varying dialysate sodium concentration. These ECV changes were followed by determining inuline in plasma and total dialysate. Changes of B2M concentration correlate well to changes of ECV (r = 0.98). Thus intratreatment concentration changes of B2M in cuprophane dialysis reflect simultaneous changes of B2M distribution volume. This does not exclude the possibility of B2M generation stimulated by dialysis, but proving such effects in vivo will be difficult because of multiple variants, that must be controlled.
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