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      Increased Serum Neutral Endopeptidase Activity in Acute Renal Allograft Rejection

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          Abstract

          Neutral endopeptidase (EC 3.4.24.11; NEP), originally isolated from renal tubular brush border, is a cell surface peptidase identical to the CD 10 antigen (or CALLA; common acute lymphoblastic leukemia antigen) in lymphoid cells. We studied the serum NEP levels daily after transplantation (Tx) in 19 renal allograft recipients. The NEP activity was determined with a two-step enzymatic assay utilizing a fluorogenic substrate (Suc-Ala-Ala-Phe-AMC; see text) and related to clinical signs of graft rejection, to signs of immunoactivation in transplant fine-needle aspiration biopsy (FNAB) specimens, to renal function, and to serum levels of C-reactive protein. The serum NEP levels remained normal (peak level 10.3 ± 1.8 µg/l on days 6-9 after Tx, initial level after Tx 7.3 ± 1.4 µg/l on day 2; mean values ± SEM) in patients who neither showed clinical signs of rejection nor had findings of immunoactivation in FNAB samples. On the contrary, the serum NEP levels rose clearly in patients developing acute rejection verified clinically and in FNAB samples (peak value 90.4 ± 18.7 µg/l on days 6-9 post-Tx; p < 0.001 compared with patients without signs of immunoactivation) and even in patients having immunoactivation in FNAB without clinical evidence of rejection (108.2 ± 22.4 µg/l, p < 0.001). Serum NEP peak appeared 2-3 days before clinical diagnosis of rejection and a positive finding in FNAB samples. Serum NEP increments did not correlate with changes in serum creatinine, delayed onset of renal excretory function, blood leukocyte count, C-reactive protein level, or infections. Thus, the serum NEP activity was shown to increase after renal allotransplantation associated with early phases of immunoactivation and development of acute graft rejection. Because of the limited number of patients studied, the clinical implications of these preliminary observations for kidney transplant monitoring clearly need confirmation in larger studies.

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          Author and article information

          Journal
          AJN
          Am J Nephrol
          10.1159/issn.0250-8095
          American Journal of Nephrology
          S. Karger AG
          0250-8095
          1421-9670
          1996
          1996
          28 October 2008
          : 16
          : 4
          : 273-279
          Affiliations
          aFourth Department of Medicine and bFourth Department of Surgery, Helsinki University Central Hospital; cTransplantation Laboratory, Helsinki University, Helsinki, Finland
          Article
          169009 Am J Nephrol 1996;16:273–279
          10.1159/000169009
          8739278
          © 1996 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.

          Page count
          Pages: 7
          Categories
          Clinical Study

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