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      Can Cystatin C Replace Creatinine to Estimate Glomerular Filtration Rate? A Literature Review

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          Background: With the increasing knowledge that estimation of glomerular filtration rate (GFR) from serum creatinine (Scr) has limited value, researchers have developed new equations based on serum cystatin C (Cys C). Aim: To compare the performance of serum Cys C and Cys C-based GFR equations to Scr and Scr-based GFR equations. Methods: A Medline literature search for studies in English. Results: Fourteen studies in kidney transplant patients and 29 in patients with native kidney disease were identified. 70% of studies on transplants favored Cys C over Scr while 60% favored serum Cys C over Scr in patients with native kidney disease. Three studies in transplant patients and 6 in patients with native kidney disease compared the performances of Cys C- and Scr-based equations. 70% of the studies performed on transplantation favored Cys C, while 85% the studies performed in native kidney diseases showed superiority of Cys C-based equations. Conclusion: A large number of studies favor Cys C over Scr for the estimation of GFR. Still, many reports show no superiority of Cys C over Scr. Consistent with this, more studies are needed to study the performance of Cys C-based GFR equations.

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          Most cited references 52

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

          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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            Some suggestions for measuring predictive performance.

            The performance of a prediction or measurement model is often evaluated by computing the correlation coefficient and/or the regression of predictions on true (reference) values. These provide, however, only a poor description of predictive performance. The mean square prediction error (precision) and the mean prediction error (bias) provide better descriptions of predictive performance. These quantities are easily computed, and can be used to compare prediction methods to absolute standards or to one another. The measures, however, are unreliable when the reference method is imprecise. The use of these measures is discussed and illustrated.
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              Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment.

              Cystatin C is a nonglycosylated basic protein produced at a constant rate by all investigated nucleated cells. It is freely filtered by the renal glomeruli and primarily catabolized in the tubuli (not secreted or reabsorbed as an intact molecule). Because serum cystatin C concentration is independent of age, sex, and muscle mass, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with serum creatinine level. We compared serum cystatin C level with other markers of GFR, such as serum creatinine level and creatinine clearance, and analyzed their variations based on iothalamate labeled with iodine 125 ((125)I-iothalamate) clearance ((125)I-ICl), used as the gold standard for GFR. The concentrations of the two different markers of GFR in patients with impaired renal function were classified according to (125)I-ICl. Twenty individuals with normal renal function ((125)I-ICl, 128 +/- 23 mL/min/1.73 m(2)) were used as the control group. Serum cystatin C level showed a greater sensitivity (93.4%) than serum creatinine level (86.8%). Also, serum cystatin C showed the greatest proportion of increased values in patients with impaired renal function (100%) compared with serum creatinine level (92.15%). Serum cystatin C levels started to increase to greater than normal values when GFR was 88 mL/min/1.73 m(2), whereas serum creatinine level began to increase when GFR was 75 mL/min/1.73 m(2). These data suggest that measurement of serum cystatin C may be useful to estimate GFR, especially to detect mild reductions in GFR, and therefore may be important in the detection of early renal insufficiency in a variety of renal diseases for which early treatment is critical.

                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                April 2007
                15 March 2007
                : 27
                : 2
                : 197-205
                aRoyal University Hospital, Department of Medicine, Division of Nephrology, University of Saskatchewan, bDivision of Nephrology, St. Paul’s Hospital, Saskatoon, Sask., Canada
                100907 Am J Nephrol 2007;27:197–205
                © 2007 S. Karger AG, Basel

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                Page count
                Tables: 5, References: 77, Pages: 9
                Original Report: Laboratory Investigation


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