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      Effect of Increased Hemodialysis Dose on Endogenous Erythropoietin Production in End-Stage Renal Disease

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          We investigated 20 patients (12 men and 8 women) with end-stage renal disease sustained on hemodialysis to determine the effect of 6 weeks of increased dialysis dose on endogenous erythropoietin production. Increased dialysis dose was achieved by increasing thrice-weekly dialysis treatment time from 4 to 4.5 h and switching from an MCA 160 dialyzer to an F80 dialyzer. The mean age of the study subjects was 51 ± 13.8 years, and the mean duration of end-stage renal disease prior to the study was 31.4 ± 55.5 months. All subjects were receiving recombinant erythropoietin for at least 4 months prior to the study. The dialysis dose was increased from a mean reduction of urea of 60.7 to 72%. At baseline, the group’s mean hematocrit was 28.4 ± 3.4%, the mean predialysis endogenous erythropoietin level was 9.1 ± 4.5 (range 2.5–18.4) mU/ml, the mean reduction of urea was 60.7 ± 4%, and the mean transferrin saturation was 22.6 ± 15.5%. Mean thrice-weekly recombinant erythropoietin injections were administered intravenously after dialysis to each patient at a dose of 51 ± 19 U/kg body weight. After 6 weeks of an increased dialysis dose, the mean hematocrit increased from 28.4 ± 3.4 to 32.3 ± 3.3% (p = 0.0001), while the mean serum endogenous erythropoietin level decreased from 9.1 ± 4.5 (range 2.5–18.4) mU/ml to 6.1 ± 3.2 (range 2.5–13.4) mU/ml (p = 0.0001). We conclude that the serum endogenous erythropoietin levels decrease with increased dialysis dose and that the increase in hematocrit following increased dialysis dose is probably not mediated by changes in endogenous erythropoietin.

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          The intensity of hemodialysis and the response to erythropoietin in patients with end-stage renal disease.

          Anemia (characterized by a hematocrit of 30 percent or lower) persists in 40 to 60 percent of patients treated for end-stage renal disease with maintenance hemodialysis, despite concomitant erythropoietin (epoetin) therapy. We tested the hypothesis that inadequate dialysis is a key reason for the insufficient response to erythropoietin in patients with end-stage renal disease who are receiving hemodialysis. We prospectively studied 135 randomly selected patients undergoing hemodialysis who had been receiving intravenous erythropoietin for at least four months. The adequacy of dialysis was assessed by measuring the percent reduction in the blood urea nitrogen concentration and the serum albumin concentration. The hematocrit was measured weekly for four weeks, transferrin saturation was measured, and coexisting illnesses were documented. To determine the effect of an increased level of dialysis on the hematocrit, the thrice-weekly schedule of dialysis was increased to raise the mean urea-reduction value from 60.7 to 72 percent for six weeks in 20 consecutive patients whose base-line urea-reduction value was less than 65 percent. The change in the hematocrit in these patients was compared with that observed in the next 20 patients who had an equivalent base-line urea-reduction value but whose level of dialysis was not altered. The mean hematocrit of the entire group was 29.2 +/- 4 percent, and the mean thrice-weekly dose of erythropoietin was 59 +/- 29 U per kilogram of body weight. The mean serum albumin concentration was 3.8 +/- 0.4 g per deciliter, the mean urea-reduction value was 62 +/- 4.8 percent, and the mean transferrin saturation was 20 +/- 9 percent. Multiple regression analysis revealed direct correlations between the hematocrit and the serum albumin concentration (P = 0.009) and between the hematocrit and the urea-reduction value (P = 0.012) after adjustment for other factors. A logistic-regression analysis indicated that an 11 percent increase in the urea-reduction value doubled the odds that a patient would have a hematocrit above 30 percent. After six weeks of increased intensity of dialysis in 20 patients with base-line urea-reduction values of less than 65 percent, the mean (+/- SE) hematocrit rose from 28.4 +/- 0.78 percent to 32.3 +/- 0.71 percent (P = 0.002); there was no significant change in a control group of 20 patients with equivalent base-line urea-reduction values in whom the dialysis level was not altered (28.2 +/- 0.84 percent to 26.3 +/- 0.85 percent; P = 0.175). In patients with end-stage renal disease, inadequate hemodialysis is associated with a suboptimal response to erythropoietin therapy. Increasing the intensity of dialysis in patients with anemia who are receiving inadequate dialysis results in a significant increase in the hematocrit.

            Author and article information

            S. Karger AG
            May 1998
            29 April 1998
            : 79
            : 1
            : 50-54
            Renal Disease Division, Department of Medicine, State University of New York Health Science Center, Brooklyn, N.Y., USA
            44991 Nephron 1998;79:50–54
            © 1998 S. Karger AG, Basel

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            Figures: 1, References: 39, Pages: 5
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