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      Influence of Relative Hypoparathyroidism on the Responsiveness to Recombinant Human Erythropoietin in Hemodialysis Patients

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          Abstract

          Background/Aim: It has been shown in a few studies examining small patient groups that high levels of intact parathyroid hormone (iPTH) were associated with a less efficient response to recombinant human erythropoietin (rHuEPO). However, the responsiveness to rHuEPO in hemodialysis (HD) patients with relative hypoparathyroidism remains undetermined. This study examines the responsiveness to rHuEPO in HD patients with relative hypoparathyroidism. Methods: We retrospectively studied 19 nondiabetic patients (mean age 44.3 ± 8.2 years, age range 29.4–55.6 years) treated with HD for chronic glomerulonephritis. Of the 19 patients, 8 (group A) had iPTH levels <100 pg/ml for the preceding 6 months without administration of 1,25-(OH)<sub>2</sub>-vitamin D<sub>3</sub>. Eleven patients had iPTH levels >100 pg/ml (group B). Hematocrit (Hct) and rHuEPO doses were recorded for statistical analysis. Results: In patients of groups A and B, the rHuEPO dose (U/kg/week) was 55.21 ± 16.23 vs. 84.08 ± 24.56 (p = 0.01); Hct (%) 33.29 ± 1.72 vs. 31.43 ± 2.98 (p = 0.67), and rHuEPO resistance index (weekly rHuEPO dose/Hct) 81.38 ± 16.64 vs. 155.63 ± 42.22 (p < 0.001). Furthermore, weekly rHuEPO dose and rHuEPO resistance index correlated positively with serum iPTH levels (R = 0.765, p < 0.001; R = 0.764, p < 0.001), whereas the Hct correlated negatively with serum iPTH levels (R = –0.400, p = 0.045). The alkaline phosphatase level (IU/l) was lower (50.46 ± 12.87 vs. 69.61 ± 20.68, p = 0.17) in group A. Conclusion: Our observations suggest that the lower the iPTH levels of chronic HD patients, even with relative hypoparathyroidism, the better the responsiveness to rHuEPO.

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          Effect of serum parathyroid hormone and bone marrow fibrosis on the response to erythropoietin in uremia.

          Anemia is common in patients with chronic renal insufficiency and secondary hyperparathyroidism. Erythropoietin therapy is effective, but the dose required varies greatly. One possible determinant of the efficacy of erythropoietin therapy is the extent of marrow fibrosis caused by hyperparathyroidism. We examined the relation between the erythropoietic response to erythropoietin and hyperparathyroidism in a cross-sectional study of 18 patients undergoing hemodialysis who had received erythropoietin therapy for one to three years. In 7 patients (the poor-response group), the dose of intravenous erythropoietin needed to maintain a mean (+/- SD) target hematocrit of 35 +/- 3 percent was > 100 units per kilogram of body weight three times a week, and in 11 patients (the good-response group) it was < or = 100 units per kilogram. In all patients, indexes of the adequacy of dialysis and the extent of hyperparathyroidism and aluminum toxicity were determined monthly, and bone histomorphometry was performed. The mean (+/- SD) dose of erythropoietin required to maintain the target hematocrit was 174 +/- 33 units per kilogram three times a week in the poor-response group and 56 +/- 18 units per kilogram in the good-response group. The mean ages, duration and adequacy of dialysis, increment in hematocrit, iron requirements, and serum concentrations of calcium, phosphate, and aluminum were similar in the two groups. The percentages of osteoid volume and surface, the osteoid thickness, and the stainable aluminum content of bone were similar in the two groups. In contrast, the mean serum parathyroid hormone concentration, the percentages of osteoclastic and eroded bone surfaces, and the degree of marrow fibrosis were greater in the poor-response group than in the good-response group (P = 0.03, P = 0.04, P = 0.009, and P = 0.009, respectively). In patients with uremia, the dose of erythropoietin needed to achieve an adequate hematocrit response may depend on the severity of secondary hyperparathyroidism and the extent of bone marrow fibrosis.
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            Erythropoietin, aluminium, and anaemia in patients on haemodialysis.

            Effects of erythropoietin treatment on haem synthesis in peripheral blood were evaluated in 11 patients on haemodialysis. After 2 weeks of erythropoietin, mean (SEM) uroporphyrinogen-l synthase activity increased significantly from 88 (10) to 116 (9) pmol/h per mg protein. Haem synthase activity, thought to be the rate-limiting step in erythroid haem synthesis, also showed a significant increase from 4.5 (0.8) to 8.4 (1.8) pmol/h per 10(6) reticulocytes. 4 patients, who showed only a partial response to erythropoietin, had significantly higher serum aluminium concentrations than the 7 who responded fully (225 [44] vs 55 [23] micrograms/l); erythrocyte protoporphyrin concentrations in partial responders were also much higher than in responders (973 [120] vs 388 [29] nmol/l). Aluminium intoxication may cause resistance to erythropoietin by interference with haem synthesis, with accumulation of protoporphyrin.
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              Reduced erythropoietin responsiveness to anemia in diabetic patients before advanced diabetic nephropathy

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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2003
                2003
                05 June 2003
                : 21
                : 3
                : 220-224
                Affiliations
                Departments of Internal Medicine, aFar Eastern Memorial Hospital and bNational Taiwan University Hospital, Taipei, Taiwan
                Article
                70693 Blood Purif 2003;21:220–224
                10.1159/000070693
                12784047
                b50adec4-a8ea-4e89-91fb-1a567e667c31
                © 2003 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 07 January 2003
                Page count
                Figures: 2, Tables: 3, References: 15, Pages: 5
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Anemia,Erythropoietin,Hemodialysis,Hypoparathyroidism
                Cardiovascular Medicine, Nephrology
                Anemia, Erythropoietin, Hemodialysis, Hypoparathyroidism

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