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      Glomerular Filtration Rate Estimation in Patients with Advanced Chronic Renal Insufficiency Based on Serum Cystatin C Levels

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          Abstract

          Background: Cystatin C has an obvious advantage in the recognition of the initial stages of renal impairment. It is questionable whether cystatin C possesses the same benefit in follow-up of pre-dialysis patients. If cystatin C were also a sensitive marker of GFR in pre-dialysis patients, then it could be expected that, for the same degree of a decrease in GFR, the increase in S<sub>cyst</sub> would be higher than in S<sub>cr</sub> because of the significant increase in tubular secretion of creatinine in residual nephrons. The aim of this study was to evaluate whether S<sub>cyst</sub> in patients with GFR ≤40 ml/min/1.73 m<sup>2</sup> provides a more accurate estimate of GFR than S<sub>cr</sub> does. Methods: The study was performed in 67 patients (mean age 41.5 ± 7.6 years) with chronic renal insufficiency (GFR = 19.8 ± 9.9 ml/min/1.73 m<sup>2</sup>) caused by various chronic renal diseases (predominantly by chronic glomerulonephritis and chronic interstitial nephritis). GFR was measured by inulin clearance under conditions of stabilized plasma concentrations and water loading. Creatinine clearance and serum cystatin C concentration (using immunonephelometry) were measured at the same time. For statistical evaluation, linear regression analysis, receiver-operating characteristic (ROC) curves analysis and the method of Bland and Altman were used. Results: A significant correlation (r = 0.813, p < 0.001) was demonstrated between 1/S<sub>cyst</sub> and C<sub>in</sub> as well as between 1/S<sub>cr</sub> and C<sub>in</sub> (r = 0.815, p < 0.001). There were no significant differences between the regression coefficients and the intercepts of regression straight lines characterizing these relationships. ROC curves analysis using the cut-off values for C<sub>in</sub> = 20 ml/min/1.73 m<sup>2</sup> and C<sub>in</sub> = 10 ml/min/ 1.73 m<sup>2</sup> did not show significant differences of corresponding AUC values for S<sub>cyst</sub> and S<sub>cr</sub> although there was a trend for superiority of S<sub>cyst</sub> in comparison with S<sub>cr</sub>. The multiples of upper reference values of S<sub>cyst</sub> and S<sub>cr</sub> in examined patients did not differ significantly. There was a highly significant linear correlation between C<sub>in</sub> and C<sub>cr</sub> in pre-dialysis patients (r = 0.921, p < 0.001). The regression coefficient of this relation (1.279) was significantly higher than 1.0 (p < 0.001) and the value of intercept (6.50 ml/min/1.73 m<sup>2</sup>) was significantly higher than zero (p < 0.001). The average of C<sub>cr</sub>/C<sub>in</sub> in patients with C<sub>in</sub> <10 ml/min/1.73 m<sup>2</sup> was 2.11 (± 0.29) and 1.72 (± 0.35) for those with C<sub>in</sub> 10–20 ml/min/1.73 m<sup>2</sup>. Conclusions: The findings suggest that in patients with advanced chronic renal insufficiency (CRI) for the same decrease in GFR the increase of S<sub>cyst</sub> is not significantly higher than that of S<sub>cr</sub>, although the tubular secretion of creatinine is significantly increased. Further studies (especially those focused on nonrenal elimination of cystatin C) are needed to elucidate the lack of difference between changes in S<sub>cyst</sub> and S<sub>cr</sub> in patients with CRI.

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          Serum cystatin C as a marker of the renal function.

          The protease inhibitor cystatin C is a non-glycosylated low molecular weight protein (Mr=13359) which is produced by all nucleated cells at a constant rate, freely filtered by the renal glomeruli, and catabolized in the tubuli. The aim of the study was to elucidate the applicability of serum cystatin C as a marker of glomerular filtration rate (GFR) in patients with various kidney diseases with a wide range of renal function and in dialysis patients. Seventy-six patients with various kidney diseases (aged 20 to 79 years) and 61 dialysis patients (aged 21 to 82 years) were included. Serum cystatin C was measured by automated particle-enhanced immunoturbidimetry, serum and urine creatinine by an enzymatic method, and GFR by 99mTc-DTPA-clearance using a single plasma sample method. Serum cystatin C in patients with various kidney diseases was 1.90+/-0.98 mg/L (mean+/-SD) and in dialysis patients 7.14+/-1.91 mg/L. In the non-dialysis patients a linear relationship was found between 99mTc-DTPA-clearance and 1/serum cystatin C (r=0.91, p-value<0.0001), 1/serum creatinine (r=0.89, p-value<0.0001), and creatinine-clearance (r=0.88, p-value<0.0001). Comparison of the non-parametric ROC plots for serum cystatin C (area under the curve (AUC)=0.9665; SE=0.0169), serum creatinine (AUC=0.9554; SE=0.0205), and creatinine-clearance (AUC=0.9731; SE=0.0160) revealed no significant differences (p-values: 0.50, 0.78, and 0.49). In conclusion, cystatin C may be a likewise good marker of the GFR as serum creatinine and creatinine-clearance, cystatin C having the advantage being independent of gender and muscle mass.
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            Cystatin for estimation of glomerular filtration rate?

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              Author and article information

              Journal
              NEC
              Nephron Clin Pract
              10.1159/issn.1660-2110
              Nephron Clinical Practice
              S. Karger AG
              1660-2110
              2003
              April 2003
              17 November 2004
              : 93
              : 4
              : c146-c151
              Affiliations
              Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
              Article
              70234 Nephron Clin Pract 2003;93:c146–c151
              10.1159/000070234
              12759583
              © 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.

              Page count
              Figures: 5, Tables: 2, References: 14, Pages: 1
              Product
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/70234
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