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      Protective Effects of B2 Preservation Solution in Comparison to a Standard Solution (Histidine-Tryptophan-Ketoglutarate/Bretschneider) in a Model of Isolated Autologous Hemoperfused Porcine Kidney

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          Abstract

          Reperfusion injuries after organ transplantation affect graft function and influence long-term graft survival. As hypothermic storage, which minimizes the extent of unspecific tissue injury after ischemia and reperfusion, is significantly influenced by the composition of preservation solutions, strategies to optimize the different components may lead to longer graft survival. In the present study the effects of the preservation solution B2 on early renal function and histopathological changes were compared to histidine-tryptophan-ketoglutarate solution (HTK, Bretschneider) in a model of isolated blood-perfused porcine kidneys. B2-preserved kidneys displayed a lower renal resistance and significantly better creatinine clearance as compared to HTK. Mean differences were also found for filtration fraction and sodium fraction reabsorption. The functional data were also related to histopathological changes. Together, these data indicate that the recently developed preservation solution B2 offers new principles of preservation and is a useful preservation solution for experimental isolated perfused kidney models. B2 may also be an interesting model for optimizing preservation within other organ perfusion models.

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          Most cited references15

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          Expression of MUC5AC and MUC5B mucins in normal and cystic fibrosis lung.

          Hypersecretion of airway mucus is a characteristic feature of chronic airway diseases like cystic fibrosis (CF) and leads via impairment of the muco-ciliary clearance and bacterial superinfection to respiratory failure. The major components of the mucus matrix forming family of mucins in the airways are MUC5AC and MUC5B. To investigate the expression of these glycoproteins in CF, immunohistochemistry was carried out on trachea, bronchi and peripheral lung obtained from CF patients and compared to normal lung tissues. MUC5AC immunohistochemistry demonstrated signals in goblet cells of the epithelial lining. Also, goblet cells inside glandular secretory ducts revealed MUC5AC-positive staining. In comparison to those from normal subjects, CF sections were characterized by inflammatory changes and goblet cell hyperplasia, resulting in increased numbers of MUC5AC-positive cells. Immunohistochemical staining for MUC5B showed abundant staining of submucosal glands and epithelial goblet cells. Inside the glands, the immunoreactivity was restricted to glandular mucous cells. MUC5AC and MUC5B are expressed in the same histological pattern in CF compared to normal tissues with an increase of MUC5AC-positive cells due to goblet cell hyper- and metaplasia.
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            Histological evaluation of proximal tubule cell injury in isolated perfused pig kidneys exposed to cold ischemia.

            Ischemic injury of the renal allograft before transplantation is a major cause of impaired graft function. Proton nuclear spectroscopy provides a useful technique for evaluating proximal tubular activity. In addition to this technique, we proposed a histological grading system for quantifying proximal tubule alterations. The aim of this study was to evaluate the histological lesions of tubule epithelial cells in the model of isolated perfused pig kidneys following 48 to 72 h of cold storage in Euro-Collins solution. Normothermic isolated perfused pig kidneys were randomized in three experimental groups : Group 1, control group; cold flush with cold heparinized solution followed by immediate reperfusion (n = 6); Group 2, 48 h of cold storage in Euro-Collins followed by reperfusion (n = 6); Group 3, 72 h of cold storage in Euro-Collins followed by reperfusion (n = 6). Proton nuclear spectroscopy of urine and biochemical studies were performed for whole renal functional evaluation during reperfusion. Optical and electron microscopy analyses of the reperfused kidneys were performed by four investigators and the degree of cell injury was assessed using 8 different criteria in a 5-scale numerical score. Numerical scores corroborate the results from NMR spectroscopy and differed significantly between the three groups studied. The degree of proximal tubule cell damage was increased with prolonged cold ischemia as shown particularly in Group 3. The results from this study showed that analysis of cell injury based on an histological grading system in the model of isolated perfused kidney allows the quantification of the degree of proximal tubule injury. Thus, such morphological system analysis could be a useful method for quantifying tubule cell injuries observed under various physiopathological conditions. Copyright 1999 Academic Press.
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              Influence of cold-storage conditions on renal function of autotransplanted large pig kidneys.

              The consequences of ischemia/reperfusion injury (IRI) on delayed graft function (DGF) and graft survival for kidney recipients remain a matter of debate. Several strategies have been proposed to reduce IRI. We have shown that adding the anti-ischemic drug trimetazidine (TMZ) to different preservation solutions had beneficial effects on the function of reperfused rat and pig kidneys. We analyzed the renal parameters of reperfused, autotransplanted large pigs following transplantation. The left kidneys were first removed and cold flushed with Euro-Collins (EC) and University of Wisconsin (UW) solutions (with or without 10-6 mol/L TMZ) and were stored for 48 hours at 4 degrees C. The kidney was then autotransplanted, and the contralateral kidneys were removed. Creatinine clearance, natriuresis, proteinuria, the degree of interstitial fibrosis, the number of CD4, CD8, and macrophage-positive cells, and the amount of vascular cell adhesion molecule-1 were analyzed on kidney biopsies taken at 2, 4 to 5, and 10 to 12 weeks after surgery. The functions of the transplanted kidneys were better preserved after cold flushing with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher, and proteinuria was lower in animals transplanted with kidneys cold flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial fibrosis and the numbers of infiltrating CD4- and CD8-positive cells. These results indicate that the condition of cold preservation may influence long-term kidney graft functions and suggest that, to a certain extent, TMZ reduces the degree of interstitial fibrosis.
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                Author and article information

                Journal
                NEP
                Nephron Physiol
                10.1159/issn.1660-2137
                Nephron Physiology
                S. Karger AG
                1660-2137
                2004
                February 2004
                27 February 2004
                : 96
                : 2
                : p52-p58
                Affiliations
                Departments of aComparative Medicine and Experimental Animal Science, bPediatric Pneumology and Immunology/Medicine, Charité School of Medicine, and cInstitute of Anatomy, Humboldt University, Berlin, Germany
                Article
                76408 Nephron Physiol 2004;96:p52–p58
                10.1159/000076408
                14988662
                2b9a7366-9bf3-4da3-8ffc-ac4f26f04462
                © 2004 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: 2, Tables: 4, References: 29, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Porcine kidney,Isolated kidney,Autologous blood perfusion,Preservation solutions

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