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      Lymphocyte Drug Sensitivity Is Useful for Prediction of the Antiproteinuric Effect and Relapse Rate in Cyclosporine Treatment for Frequent-Relapse Minimal Change Nephrotic Syndrome

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          Abstract

          Background/Aims: The therapeutic effect of cyclosporine A (CsA) in combination with steroids varies greatly for frequent-relapse minimal change nephrotic syndrome (FRMCNS). The association between the sensitivity of peripheral blood lymphocytes (PBLs) to CsA in vitro and the therapeutic effect of CsA in FRMCNS were investigated. Methods: The sensitivity of PBLs in vitro and the therapeutic effect of CsA in 23 FRMCNS patients were compared. The length of time to complete remission (CR) and the number of relapses were compared using the 50% inhibitory concentration (IC<sub>50</sub>) of CsA in the presence of a T-cell mitogen. Results: FRMCNS patients were divided into 2 groups: a low sensitivity group with an IC<sub>50</sub> of >14.8 ng/ml (GII, n = 10), and a high sensitivity group with an IC<sub>50</sub> of <14.8 ng/ml (GI, n = 13). Comparison of the length of time to CR between the 2 groups showed that GI reached CR earlier than GII (p < 0.01). GI had significantly fewer relapses than GII when CsA was administered for 12 months or longer (p < 0.01). Conclusion: Lymphocyte sensitivity to CsA has the potential to be an important clinical indicator of the antiproteinuric effect and relapse rate in FRMCNS.

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          Most cited references 2

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          Suppression of dialysis patients' lymphocyte IL-2R expression by glucocorticoids and cyclosporine.

          Previous studies have shown interindividual heterogeneity in the suppressive effects of glucocorticoids and cyclosporine (CsA) on the proliferation responses of dialysis patients' peripheral blood mononuclear cells (PBMC). In addition, methylprednisolone (MP) was shown to be significantly more suppressive than prednisolone (P), and PBMC from patients on peritoneal dialysis (PD) were found to be more sensitive to both glucocorticoids than those from patients on haemodialysis (HD). In order to begin to explore the cellular mechanism(s) underlying these observations, the differential suppressive effects of these drugs on lymphocyte interleukin 2 receptor (IL-2R) expression by mitogen-stimulated PBMC from 23 PD and 30 HD were determined. The mean+/-SD concentrations (ng/ml) of steroid causing 50% inhibition (IC50) of cell proliferation was significantly lower for PD than HD PBMC with both P (94+/-93 vs 148+/-105, P<0.05) and MP (21+/-25 vs 35+/-31, P<0.05). MP was significantly (P<0.001) more suppressive than P of IL-2R expression in both PD and HD. PD IL-2R expression was significantly (P<0.05) more suppressed by CsA alone and by 400 ng/ml CsA+10(-7) MP than was HD IL-2R expression. CsA+10(-7) M MP was significantly (P<0.001) more suppressive of IL-2R expression than the other drugs, alone or in combination, in both groups of patients. In conclusion, these results support the notion that at least one mechanism underlying the significantly greater efficacy of MP compared to P in suppressing PBMC proliferation is its significantly greater suppression of lymphocyte IL-2R expression, either alone or in combination with CsA. Thus, use of MP following allograft transplantation may result in more effective immunosuppression for many recipients.
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            Clinical impact of cyclosporine cellular pharmacodynamics in minimal change nephrotic syndrome

             T HIRANO (2000)
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              Author and article information

              Journal
              KBR
              Kidney Blood Press Res
              10.1159/issn.1420-4096
              Kidney and Blood Pressure Research
              S. Karger AG
              1420-4096
              1423-0143
              2005
              December 2005
              27 December 2005
              : 28
              : 4
              : 226-229
              Affiliations
              aRenal Unit, Department of Internal Medicine, Hachioji Medical Center, Tokyo Medical University, and bDepartment of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
              Article
              87768 Kidney Blood Press Res 2005;28:226–229
              10.1159/000087768
              16118505
              © 2005 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
              Figures: 1, Tables: 3, References: 6, Pages: 4
              Product
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/87768
              Categories
              Rapid Communication

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