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Reviews |
1 Washington University School of Medicine, Department of Pathology and Immunology, Division of Laboratory Medicine, Box 8118, 660 S. Euclid Ave., St. Louis, MO 63110.
2 Department of Clinical Biochemistry, St. Barts and the Royal London School of Medicine, Turner Street, London E1 2AD, England.
aAuthor for correspondence. Fax 314-362-1461; e-mail mscott{at}labmed.wustl.edu.
Background: Glomerular filtration rate (GFR) is routinely assessed by measuring the concentrations of endogenous serum markers such as blood urea nitrogen and serum creatinine (SCr). Although widely used, these endogenous markers are not ideal and do not perform optimally in certain clinical settings. The purpose of this review is to critically review the potential utility of cystatin C (CysC), especially in patient populations in which CysC may have an advantage over routinely used endogenous markers of GFR.
Approach: In a narrative approach, we extensively review publications, primarily from the last 5 years, that address the development of methods to measure CysC, reference intervals, and the diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001 Medline was searched using "cystatin c" as a textword, and articles that examined >75 individuals (except for renal transplant studies) and/or used accepted "gold standards" for assessing GFR were selected for inclusion. A total of 17 studies are reviewed that provide reference interval data for several populations. A total of 24 studies make conclusions about the utility of CysC vs SCr and/or creatinine clearance, with 20 providing data on the sensitivity and specificity of CysC for detecting impaired GFR. These publications are organized into subgroups that deal with specific patient populations or clinical situations.
Content: This review focuses on two areas: (a) the evolution of immunoassays used to determine the concentration of CysC in serum, their analytic sensitivity, and reference intervals; and (b) the diagnostic performance of CysC against other renal markers in the general population and in specific subpopulations of patients.
Summary: Studies of reference intervals for CysC overwhelmingly demonstrated that CysC values in blood are independent of age and sex. Of the 24 studies that examined clinical utility, 15 concluded that CysC is superior to SCr, whereas 9 concluded that CysC is equivalent but provides no advantage. Summary ROC plot analysis of 20 studies that provide sensitivity and specificity data strongly suggests that CysC will be superior to SCr for detecting impaired GFR. Taken together, it is clear that CysC performs at least as well as SCr in the population at large and that it is likely to be superior to SCr in specific patient populations.
The following articles in journals at HighWire Press have cited this article:
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  G. J. Schwartz and D. F. Work Measurement and Estimation of GFR in Children and Adolescents Clin. J. Am. Soc. Nephrol., November 1, 2009; 4(11): 1832 - 1843. [Abstract] [Full Text] [PDF]
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N. Al-Malki, P. A. Heidenheim, G. Filler, A. Yasin, and R. M. Lindsay Cystatin C Levels in Functionally Anephric Patients Undergoing Dialysis: The Effect of Different Methods and Intensities Clin. J. Am. Soc. Nephrol., October 1, 2009; 4(10): 1606 - 1610. [Abstract] [Full Text] [PDF]
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 E. Selvin, A. Kottgen, and J. Coresh Kidney function estimated from serum creatinine and cystatin C and peripheral arterial disease in NHANES 1999-2002 Eur. Heart J., August 1, 2009; 30(15): 1918 - 1925. [Abstract] [Full Text] [PDF]
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 U. Alehagen, U. Dahlstrom, and T. L. Lindahl Cystatin C and NT-proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients with heart failure: results from a 10-year study in primary care Eur J Heart Fail, April 1, 2009; 11(4): 354 - 360. [Abstract] [Full Text] [PDF]
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 M. D. McMurray, J. E. Trivax, and P. A. McCullough Serum Cystatin C, Renal Filtration Function, and Left Ventricular Remodeling Circ Heart Fail, March 1, 2009; 2(2): 86 - 89. [Full Text] [PDF]
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T. Keller, C. M. Messow, E. Lubos, V. Nicaud, P. S. Wild, H. J. Rupprecht, C. Bickel, S. Tzikas, D. Peetz, K. J. Lackner, et al. Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the AtheroGene study Eur. Heart J., February 1, 2009; 30(3): 314 - 320. [Abstract] [Full Text] [PDF]
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 M. Kimmel and D. M. Alscher Reply Nephrol. Dial. Transplant., December 1, 2008; 23(12): 4079 - 4080. [Full Text] [PDF]
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 E. Nerpin, U. Riserus, E. Ingelsson, J. Sundstrom, M. Jobs, A. Larsson, S. Basu, and J. Arnlov Insulin Sensitivity Measured With Euglycemic Clamp Is Independently Associated With Glomerular Filtration Rate in a Community-Based Cohort Diabetes Care, August 1, 2008; 31(8): 1550 - 1555. [Abstract] [Full Text] [PDF]
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A. C. Baxmann, M. S. Ahmed, N. C. Marques, V. B. Menon, A. B. Pereira, G. M. Kirsztajn, and I. P. Heilberg Influence of Muscle Mass and Physical Activity on Serum and Urinary Creatinine and Serum Cystatin C Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 348 - 354. [Abstract] [Full Text] [PDF]
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M. Tidman, P. Sjostrom, and I. Jones A Comparison of GFR estimating formulae based upon s-cystatin C and s-creatinine and a combination of the two Nephrol. Dial. Transplant., January 1, 2008; 23(1): 154 - 160. [Abstract] [Full Text] [PDF]
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 D. M. Maahs, L. G. Ogden, A. Kretowski, J. K. Snell-Bergeon, G. L. Kinney, T. Berl, and M. Rewers Serum Cystatin C Predicts Progression of Subclinical Coronary Atherosclerosis in Individuals With Type 1 Diabetes Diabetes, November 1, 2007; 56(11): 2774 - 2779. [Abstract] [Full Text] [PDF]
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J. Lassus, V.-P. Harjola, R. Sund, K. Siirila-Waris, J. Melin, K. Peuhkurinen, K. Pulkki, M. S. Nieminen, and for the FINN-AKVA Study group Prognostic value of cystatin C in acute heart failure in relation to other markers of renal function and NT-proBNP Eur. Heart J., August 1, 2007; 28(15): 1841 - 1847. [Abstract] [Full Text] [PDF]
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R. P. Donahue, S. Stranges, K. Rejman, L. B. Rafalson, J. Dmochowski, and M. Trevisan Elevated Cystatin C Concentration and Progression to Pre-Diabetes: The Western New York Study Diabetes Care, July 1, 2007; 30(7): 1724 - 1729. [Abstract] [Full Text] [PDF]
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D. Singh, M. A. Whooley, J. H. Ix, S. Ali, and M. G. Shlipak Association of cystatin C and estimated GFR with inflammatory biomarkers: the Heart and Soul Study Nephrol. Dial. Transplant., April 1, 2007; 22(4): 1087 - 1092. [Abstract] [Full Text] [PDF]
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K. Kaartinen, J. Syrjanen, I. Porsti, A. Harmoinen, A. Pasternack, H. Huhtala, O. Niemela, and J. Mustonen Insulin resistance and the progression of IgA glomerulonephritis Nephrol. Dial. Transplant., March 1, 2007; 22(3): 778 - 783. [Abstract] [Full Text] [PDF]
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 T. Kempf, R. Horn-Wichmann, G. Brabant, T. Peter, T. Allhoff, G. Klein, H. Drexler, N. Johnston, L. Wallentin, and K. C. Wollert Circulating Concentrations of Growth-Differentiation Factor 15 in Apparently Healthy Elderly Individuals and Patients with Chronic Heart Failure as Assessed by a New Immunoradiometric Sandwich Assay Clin. Chem., February 1, 2007; 53(2): 284 - 291. [Abstract] [Full Text] [PDF]
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 M. Zaffanello, M. Franchini, and V. Fanos Is Serum Cystatin-C a Suitable Marker of Renal Function in Children? Ann. Clin. Lab. Sci., January 1, 2007; 37(3): 233 - 240. [Abstract] [Full Text] [PDF]
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 M. C. Odden, G. M. Chertow, L. F. Fried, A. B. Newman, S. Connelly, S. Angleman, T. B. Harris, E. M. Simonsick, M. G. Shlipak, and for the HABC Study Cystatin C and Measures of Physical Function in Elderly Adults: The Health, Aging, and Body Composition (HABC) Study Am. J. Epidemiol., December 15, 2006; 164(12): 1180 - 1189. [Abstract] [Full Text] [PDF]
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 J. Coresh and B. Astor Decreased Kidney Function in the Elderly: Clinical and Preclinical, Neither Benign Ann Intern Med, August 15, 2006; 145(4): 299 - 301. [Full Text] [PDF]
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 L. A. Stevens, J. Coresh, T. Greene, and A. S. Levey Assessing kidney function--measured and estimated glomerular filtration rate. N. Engl. J. Med., June 8, 2006; 354(23): 2473 - 2483. [Full Text] [PDF]
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L. K. van Rossum, R. Zietse, A. G. Vulto, and Y. B. de Rijke Renal extraction of cystatin C vs 125I-iothalamate in hypertensive patients Nephrol. Dial. Transplant., May 1, 2006; 21(5): 1253 - 1256. [Abstract] [Full Text] [PDF]
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 M. E. Alnaeb, F. Youssef, D. P. Mikhailidis, and G. Hamilton Short-term Lipid-Lowering Treatment with Atorvastatin Improves Renal Function But Not Renal Blood Flow Indices in Patients with Peripheral Arterial Disease Angiology, January 1, 2006; 57(1): 65 - 71. [Abstract] [PDF]
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G. L. Myers, W. G. Miller, J. Coresh, J. Fleming, N. Greenberg, T. Greene, T. Hostetter, A. S. Levey, M. Panteghini, M. Welch, et al. Recommendations for Improving Serum Creatinine Measurement: A Report from the Laboratory Working Group of the National Kidney Disease Education Program Clin. Chem., January 1, 2006; 52(1): 5 - 18. [Abstract] [Full Text] [PDF]
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 C. White, A. Akbari, N. Hussain, L. Dinh, G. Filler, N. Lepage, and G. A. Knoll Estimating Glomerular Filtration Rate in Kidney Transplantation: A Comparison between Serum Creatinine and Cystatin C-Based Methods J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3763 - 3770. [Abstract] [Full Text] [PDF]
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L. A. Stevens and A. S. Levey Chronic Kidney Disease in the Elderly -- How to Assess Risk N. Engl. J. Med., May 19, 2005; 352(20): 2122 - 2124. [Full Text] [PDF]
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S. A.R. Kort, A. A. Bouman, M. A. Blankenstein, and A. Bokenkamp Cystatin C Can Be Measured Reliably in Capillary Blood Samples Clin. Chem., May 1, 2005; 51(5): 903 - 904. [Full Text] [PDF]
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B. A. Perkins, R. G. Nelson, B. E.P. Ostrander, K. L. Blouch, A. S. Krolewski, B. D. Myers, and J. H. Warram Detection of Renal Function Decline in Patients with Diabetes and Normal or Elevated GFR by Serial Measurements of Serum Cystatin C Concentration: Results of a 4-Year Follow-Up Study J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1404 - 1412. [Abstract] [Full Text] [PDF]
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 A. Hoppe, S. Seronie-Vivien, F. Thomas, J.-P. Delord, L. Malard, P. Canal, and E. Chatelut Serum Cystatin C is a Better Marker of Topotecan Clearance than Serum Creatinine Clin. Cancer Res., April 15, 2005; 11(8): 3038 - 3044. [Abstract] [Full Text] [PDF]
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U. Poge, T. Gerhardt, A. Bokenkamp, B. Stoffel-Wagner, H.-U. Klehr, T. Sauerbruch, and R. P. Woitas Time course of low molecular weight proteins in the early kidney transplantation period--influence of corticosteroids Nephrol. Dial. Transplant., November 1, 2004; 19(11): 2858 - 2863. [Abstract] [Full Text] [PDF]
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 T. Jernberg, B. Lindahl, S. James, A. Larsson, L.-O. Hansson, and L. Wallentin Cystatin C: A Novel Predictor of Outcome in Suspected or Confirmed Non-ST-Elevation Acute Coronary Syndrome Circulation, October 19, 2004; 110(16): 2342 - 2348. [Abstract] [Full Text] [PDF]
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E. J. Lamb, H. J. Stowe, D. E. Simpson, A. J. Coakley, D. J. Newman, and M. Leahy Diagnostic Accuracy of Cystatin C as a Marker of Kidney Disease in Patients with Multiple Myeloma: Calculated Glomerular Filtration Rate Formulas Are Equally Useful Clin. Chem., October 1, 2004; 50(10): 1848 - 1851. [Full Text] [PDF]
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J. J. Meier, M. A. Nauck, D. Kranz, J. J. Holst, C. F. Deacon, D. Gaeckler, W. E. Schmidt, and B. Gallwitz Secretion, Degradation, and Elimination of Glucagon-Like Peptide 1 and Gastric Inhibitory Polypeptide in Patients with Chronic Renal Insufficiency and Healthy Control Subjects Diabetes, March 1, 2004; 53(3): 654 - 662. [Abstract] [Full Text] [PDF]
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 J. P. Sokol and W. P. Schiemann Cystatin C Antagonizes Transforming Growth Factor {beta} Signaling in Normal and Cancer Cells Mol. Cancer Res., March 1, 2004; 2(3): 183 - 195. [Abstract] [Full Text] [PDF]
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A. Harmoinen, T. Lehtimaki, M. Korpela, V. Turjanmaa, and H. Saha Diagnostic Accuracies of Plasma Creatinine, Cystatin C, and Glomerular Filtration Rate Calculated by the Cockcroft-Gault and Levey (MDRD) Formulas Clin. Chem., July 1, 2003; 49(7): 1223 - 1225. [Full Text] [PDF]
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B. Wuyts, D. Bernard, N. Van Den Noortgate, J. Van De Walle, B. Van Vlem, R. De Smet, F. De Geeter, R. Vanholder, and J. R. Delanghe Reevaluation of Formulas for Predicting Creatinine Clearance in Adults and Children, Using Compensated Creatinine Methods Clin. Chem., June 1, 2003; 49(6): 1011 - 1014. [Full Text] [PDF]
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A. Lupovitch and M. G. Scott More Accurate Alternatives to Serum Creatinine for Evaluating Glomerular Filtration Rate * Dr. Mitchell G. Scott responds: Clin. Chem., December 1, 2002; 48(12): 2297 - 2298. [Full Text] [PDF]
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R. Star, T. Hostetter, and G. L. Hortin New Markers for Kidney Disease Clin. Chem., September 1, 2002; 48(9): 1375 - 1376. [Full Text] [PDF]
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