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      Erythropoietin Is Beneficial in Mitomycin-Induced Hemolytic-Uremic Syndrome

      case-report
      a , b , a
      Nephron
      S. Karger AG
      Mitomycin, Hemolytic-uremic syndrome, Erythropoietin

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          Abstract

          Mitomycin C is a powerful antineoplastic agent. If used at high dosage, it may cause a secondary form of adult hemolytic-uremic syndrome (HUS). Blood transfusions worsen the evolution of this peculiar form of HUS. We describe a patient who developed HUS after treatment with mitomycin C (total dose 144 mg/m<sup>2</sup>) due to a carcinoma of the ascending colon. Repeated blood transfusions were associated with rapidly evolving renal failure coupled with anemia and thrombocytopenia. Haptoglobin was undetectable. Soon after starting subcutaneous erythropoietin, the velocity of progression of renal failure slowed whilst no more blood transfusions were required and haptoglobin levels returned to normal. Thereafter, the patient’s renal function slowly worsened and she started chronic hemodialysis 5 years later. Up to now, all investigations have failed to show a relapse of her adenocarcinoma. A possible explanation of these data is that erythropoietin permitted the termination of blood transfusions which both triggered and perpetuated the syndrome. However, we cannot exclude a primitive effect of erythropoietin on the endothelium or on the platelets.

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          Evidence for amelioration of endothelial cell dysfunction by erythropoietin therapy in predialysis patients.

          Evidence for the involvement of endothelial cells in the pathogenesis or erythropoietin-induced hypertension, and for endothelial cell damage in patients with chronic renal failure, has emerged and appears to be of major concern. We, therefore, investigated the effect of recombinant human erythropoietin (rHuEPO) therapy on endothelium-derived hormones in predialysis patients with progressive renal anemia. At the entry to the trial, the serum thrombomodulin concentration (Tm) and plasma endothelin-1 concentration (ET-1) in the predialysis patients were significantly higher than those in age- and sex-matched normal subjects. Following a 16 week period of treatment with 6000IU rHuEPO given intravenously once a week, patients' hematocrit increased from 27.1 +/- 2.6% to 34.6 +/- 3.2% (n = 16, P < .001). A positive correlation was found between Tm and serum creatinine concentration (Cr) (r = 0.61, P < .05 (n = 16), but no correlation was found between ET-1 and Cr. Tm and Tm/Cr significantly decreased from 7.9 +/- 2.8 ng/mL to 6.6 +/- 2.4 ng/mL (P < .01, n = 16), and from 2.1 +/- 0.7 (x10(-10) to 1.6 +/- 0.7 (x10(-10), P < .01, n = 16), respectively. However, there was no change in ET-1 as a result of the rHuEPO therapy. Creatinine clearance (Ccr), Cr, total amount of daily Tm excretion, Tm clearance/Ccr, daily urinary protein and albumin excretion, and blood pressure also remained unchanged throughout the trail. The present study indicates that correcting anemia by rHuEPO therapy reduces an abnormally elevated Tm in predialysis patients while blood pressure and renal function remain unchanged, suggesting that rHuEPO has a beneficial effect on endothelial cell dysfunction in chronic renal failure patients. This effect may be mediated via an improved oxygen supply to the endothelial cells due to the amelioration of anemia by rHuEPO.
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            Author and article information

            Journal
            NEF
            Nephron
            10.1159/issn.1660-8151
            Nephron
            S. Karger AG
            1660-8151
            2235-3186
            2002
            June 2002
            03 June 2002
            : 91
            : 2
            : 324-326
            Affiliations
            aRenal and Dialysis Unit and bMedico-Geriatric Department, ULSS 17, Monselice (Padova), Italy
            Article
            58411 Nephron 2002;91:324–326
            10.1159/000058411
            12053072
            f68065f1-f148-468b-a055-9f699efb3c88
            © 2002 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
            Page count
            Figures: 1, References: 14, Pages: 3
            Categories
            Case Report

            Cardiovascular Medicine,Nephrology
            Mitomycin,Hemolytic-uremic syndrome,Erythropoietin
            Cardiovascular Medicine, Nephrology
            Mitomycin, Hemolytic-uremic syndrome, Erythropoietin

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