Serum Cystatin C-Based Formulas for Prediction of Glomerular Filtration Rate in Patients with Chronic Kidney Disease

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Abstract

Background: The present study, involving a large group of patients with chronic kidney disease (CKD), compares different serum cystatin C-based equations for prediction of the glomerular filtration rate (GFR). Methods: A total of 592 adult patients with CKD were enrolled in the study. Serum cystatin C was determined in each patient by an immunonephelometric method. Their GFR was estimated using 5 equations based on serum cystatin C: (1) the Larsson formula, (2) the Hoek formula, (3) the Grubb formula, (4) the simple cystatin C formula (GFR = 100/cystatin C) and (5) our own cystatin C formula (GFR = 90.63 × cystatin C–1.192). The actual GFR was measured using 51CrEDTA clearance. Results: The mean 51CrEDTA clearance was 47 ml/min/1.73 m2; the mean serum cystatin C concentration was 2.68 mg/l. Receiver operating characteristic curve analysis (cutoff for GFR: 60 ml/min/ 1.73 m2) showed no difference between the cystatin C formulas with regard to diagnostic accuracy. All equations underestimated the measured GFR except the simple cystatin C formula, which slightly overestimated the measured GFR. All equations lacked precision. The ability to correctly estimate the patient’s GFR was high for all equations (87.3–91.9%), except for the Larsson formula, with which 29.2% of subjects were misclassified. Conclusions: Our results indicate that all serum cystatin C-based equations, excluding the Larsson formula, are reliable markers of the GFR in patients with CKD, and for daily clinical practice the simplest formula (100/cystatin C) could be accurate enough for GFR estimation.

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Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis.

Vikas R. Dharnidharka, Charles Kwon, Gary Stevens (2002)

Serum cystatin C (Cys C) has been proposed as a simple, accurate, and rapid endogenous marker of glomerular filtration rate (GFR) in research and clinical practice. However, there are conflicting reports regarding the superiority of Cys C over serum creatinine (Cr), with a few studies suggesting no significant difference. We performed a meta-analysis of available data from various studies to compare the accuracy of Cys C and Cr in relation to a reference standard of GFR. A bibliographic search showed 46 articles until December 31, 2001. We also retrieved data from eight other studies presented and published in abstract form. The overall correlation coefficient for the reciprocal of serum Cys C (r = 0.816; 95% confidence interval [CI], 0.804 to 0.826) was superior to that of the reciprocal of serum Cr (r = 0.742; 95% CI, 0.726 to 0.758; P < 0.001). Similarly, receiver operating characteristic (ROC)-plot area under the curve (AUC) values for 1/Cys C had greater identity with the reference test for GFR (mean ROC-plot AUC for Cys C, 0.926; 95% CI, 0.892 to 0.960) than ROC-plot AUC values for 1/Cr (mean ROC-plot AUC for serum Cr, 0.837; 95% CI, 0.796 to 0.878; P < 0.001). Immunonephelometric methods of Cys C assay produced significantly greater correlations than other assay methods (r = 0.846 versus r = 0.784; P < 0.001). In this meta-analysis using currently available data, serum Cys C is clearly superior to serum Cr as a marker of GFR measured by correlation or mean ROC-plot AUC. Copyright 2002 by the National Kidney Foundation, Inc.

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Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program.

G. Myers (2006)

Reliable serum creatinine measurements in glomerular filtration rate (GFR) estimation are critical to ongoing global public health efforts to increase the diagnosis and treatment of chronic kidney disease (CKD). We present an overview of the commonly used methods for the determination of serum creatinine, method limitations, and method performance in conjunction with the development of analytical performance criteria. Available resources for standardization of serum creatinine measurement are discussed, and recommendations for measurement improvement are given. The National Kidney Disease Education Program (NKDEP) Laboratory Working Group reviewed problems related to serum creatinine measurement for estimating GFR and prepared recommendations to standardize and improve creatinine measurement. The NKDEP Laboratory Working Group, in collaboration with international professional organizations, has developed a plan that enables standardization and improved accuracy (trueness) of serum creatinine measurements in clinical laboratories worldwide that includes the use of the estimating equation for GFR based on serum creatinine concentration that was developed from the Modification of Diet in Renal Disease (MDRD) study. The current variability in serum creatinine measurements renders all estimating equations for GFR, including the MDRD Study equation, less accurate in the normal and slightly increased range of serum creatinine concentrations [<133 micromol/L (1.5 mg/dL)], which is the relevant range for detecting CKD [<60 mL.min(-1).(1.73 m2)(-1)]. Many automated routine methods for serum creatinine measurement meet or exceed the required precision; therefore, reduction of analytical bias in creatinine assays is needed. Standardization of calibration does not correct for analytical interferences (nonspecificity bias). The bias and nonspecificity problems associated with some of the routine methods must be addressed.

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Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function.

M Paillard, Jerome Rossert, Marc Froissart … (2005)

Recent recommendations emphasize the need to assess kidney function using creatinine-based predictive equations to optimize the care of patients with chronic kidney disease. The most widely used equations are the Cockcroft-Gault (CG) and the simplified Modification of Diet in Renal Disease (MDRD) formulas. However, they still need to be validated in large samples of subjects, including large non-U.S. cohorts. Renal clearance of (51)Cr-EDTA was compared with GFR estimated using either the CG equation or the MDRD formula in a cohort of 2095 adult Europeans (863 female and 1232 male; median age, 53.2 yr; median measured GFR, 59.8 ml/min per 1.73 m(2)). When the entire study population was considered, the CG and MDRD equations showed very limited bias. They overestimated measured GFR by 1.94 ml/min per 1.73 m(2) and underestimated it by 0.99 ml/min per 1.73 m(2), respectively. However, analysis of subgroups defined by age, gender, body mass index, and GFR level showed that the biases of the two formulas could be much larger in selected populations. Furthermore, analysis of the SD of the mean difference between estimated and measured GFR showed that both formulas lacked precision; the CG formula was less precise than the MDRD one in most cases. In the whole study population, the SD was 15.1 and 13.5 ml/min per 1.73 m(2) for the CG and MDRD formulas, respectively. Finally, 29.2 and 32.4% of subjects were misclassified when the CG and MDRD formulas were used to categorize subjects according to the Kidney Disease Outcomes Quality Initiative chronic kidney disease classification, respectively.

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Journal

Journal ID (publisher-id): NEC

Journal ID (nlm-ta): Nephron Clin Pract

Journal ID (doi): 10.1159/issn.1660-2110

Title: Nephron Clinical Practice

Publisher: S. Karger AG

ISSN (Electronic): 1660-2110

Publication date Subscription-year: 2010

Publication date (Print): February 2010

Publication date (Electronic): 03 November 2009

Volume: 114

Issue: 2

Pages: c118-c126

Affiliations

Departments of ^aNephrology and ^bNuclear Medicine, Clinic of Internal Medicine, and ^cDepartment of Clinical Chemistry, University Medical Center Maribor, Maribor, Slovenia

Article

Publisher ID: 254384 Other ID: Nephron Clin Pract 2010;114:c118–c126

DOI: 10.1159/000254384

PubMed ID: 19887832

SO-VID: f6954786-6e00-43d7-a7c1-ad9a94373a24

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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

Date received : 06 April 2009

Date accepted : 09 July 2009

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Figures: 1, Tables: 4, References: 27, Pages: 1

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Serum Cystatin C-Based Formulas for Prediction of Glomerular Filtration Rate in Patients with Chronic Kidney Disease

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Karger: Nephrology

Most cited references 18

Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis.

Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program.

Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function.

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