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      Did Creatinine Standardization Give Benefits to the Evaluation of Glomerular Filtration Rate?

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          Abstract

          During the last decade, a lot of efforts has been made to improve the evaluation of renal functions. Measured Glomerular Filtration Rate (GFR) remains the only valuable test to confirm or confute the status of chronic kidney disease (CKD) and is recommended by Kidney Disease Global Outcomes guidelines when estimation of GFR is not reliable. However, in routine clinical practice, serum creatinine remains the one of the most prescribed biological parameters and is an undeniable factor, alone or in association with other parameters, of the estimation of GFR. Since many years, a great improvement in the creatinine measurements was realized because of the standardization of the methods and fabrication of an international standard with concentration near to physiological ones (SRM967). Standardization according to Isotopic Dilution Mass Spectrometry dramatically improves the analytical performances of creatinine assays resulting in a more accurate estimation of GFR using creatinine based equations. Indeed, the standardization of creatinine improves the analytical performance by reducing the bias and removing the influence of the interfering substances.

          However, biological variability of creatinine is not affected by analytical standardization and remains a limitation to the use of creatinine in some selected populations, having extreme ages or weights like children, elderly subjects, obese or malnourished populations. Standardization of creatinine assays result in a clear improvement of estimated GFR in general population but alternative methods should be used when creatinine production or metabolism is impaired.

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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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            Limitations of creatinine as a filtration marker in glomerulopathic patients.

            To determine the reliability of creatinine as a measure of the glomerular filtration rate (GFR), we compared the simultaneous clearance of creatinine to that of three true filtration markers of graded size in 171 patients with various glomerular diseases. Using inulin (radius [rs] = 15 A) as a reference marker, we found that the fractional clearance of 99mTc-DTPA (rs = 4 A) was 1.02 +/- 0.14, while that of a 19 A rs dextran was 0.98 +/- 0.13, with neither value differing from unity. In contrast, the fractional clearance (relative to inulin) of creatinine (rs = 3 A) exceeded unity, averaging 1.64 +/- 0.05 (P less than 0.001), but could be lowered towards unity by acute blockade of tubular creatinine secretion by IV cimetidine. Cross-sectional analysis of all 171 patients revealed fractional creatinine secretion to vary inversely with GFR. This inverse relationship was confirmed also among individual patients with either deteriorating (N = 28) or remitting (N = 26) glomerular disease, who were studied longitudinally. As a result, changes in creatinine relative to inulin clearance were blunted considerably or even imperceptible. We conclude that true filtration markers with rs less than 20 A, including inulin, are unrestricted in glomerular disease, and that creatinine is hypersecreted progressively by remnant renal tubules as the disease worsens. Accordingly, attempts to use creatinine as a marker with which to evaluate or monitor glomerulopathic patients will result in gross and unpredictable overestimates of the GFR.
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              Measurement of renal function in chronic renal disease.

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                Author and article information

                Journal
                EJIFCC
                EJIFCC
                eJIFCC
                EJIFCC
                The Communications and Publications Division (CPD) of the IFCC
                1650-3414
                19 December 2017
                December 2017
                : 28
                : 4
                : 251-257
                Affiliations
                [1 ] Department of Biochemistry and Hormonology, CHU de Montpellier, PhyMedExp, University of Montpellier , France
                [2 ] Department of Clinical Chemistry, Sart Tilman Hospital and University of Liège , Belgium
                [3 ] Department of Nephrology Dialysis Transplantation, Sart Tilman Hospital and University of Liège , Belgium
                [4 ] On behalf of the Société Française de Biologie Clinique
                Author notes
                Department of Biochemistry and Hormonology CHU de Montpellier 371, Avenue du Doyen Gaston Giraud 34295 Montpellier Cedex 5 France jp-cristol@ 123456chu-montpellier.fr
                Article
                ejifcc-28-251
                5746834
                29333144
                a133ecec-597b-4591-8dbe-cba048abbd39
                Copyright © 2017 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 45, Pages: 7
                Categories
                Research Article

                creatinine,standardization,glomerular filtration rate

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