title: Cystatin C--a paradigm of evidence based laboratory medicine.
abstract: Cystatin C is a 13-kDa protein, of the cysteine proteinase inhibitor superfamily, produced by all nucleated cells. Its production rate is constant throughout the ages of 1 to 50 years. It is freely filtered at the glomerulus and then resorbed and fully catabolised by proximal renal tubules, making it an ideal marker of glomerular filtration rate (GFR). Serum creatinine, the most established marker of renal function, is affected by age, gender, muscle mass, nutritional status and analytical interference. The abbreviated Modification of Diet in Renal Diseases (MDRD) equation has recently been introduced in an attempt to overcome these shortcomings, but still has many limitations. Cystatin C is not affected by gender, muscle mass, malignancy, its production rate is usually constant and its plasma concentration therefore is dependent only on GFR. Cystatin C has been demonstrated to be more accurate than serum creatinine in the detection of early renal impairment and in specific populations may allow for early detection of renal disease. Cystatin C has also been found to be a strong predictor of long-term clinical outcomes in patients with cardiovascular diseases. Although cystatin C may have advantages in detection of early renal impairment there is a paucity of evidence that it significantly improves clinical decision making over creatinine. This coupled with assay cost may be the reason why cystatin C, although well recognised, has not been introduced into routine operational use, although that may eventuate with emerging evidence.
authors.affiliation: Department of Biochemistry, Medlab South Ltd, Christchurch, New Zealand.
authors.forename: Janice S C
authors.initials: JS
authors.lastname: Chew
authors.forename: Mohammed
authors.initials: M
authors.lastname: Saleem
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Florkowski
authors.forename: Peter M
authors.initials: PM
authors.lastname: George
references.citation: Am J Kidney Dis. 2008 Mar;51(3):395-406
references.pmid: 18295055
references.citation: Crit Rev Clin Lab Sci. 1989;27(5):409-37
references.pmid: 2679660
references.citation: Scand J Clin Lab Invest. 1979 Nov;39(7):619-26
references.pmid: 119302
references.citation: Clin Chem. 2005 Feb;51(2):321-7
references.pmid: 15563478
references.citation: Clin Chem. 2001 Aug;47(8):1482-5
references.pmid: 11468246
references.citation: Diabetes Care. 2002 Nov;25(11):2004-9
references.pmid: 12401747
references.citation: Clin Chem. 2007 Mar;53(3):480-8
references.pmid: 17259236
references.citation: Scand J Clin Lab Invest. 2005;65(2):153-62
references.pmid: 16025838
references.citation: Am J Kidney Dis. 2001 Jan;37(1):79-83
references.pmid: 11136171
references.citation: Arch Dis Child. 1976 Nov;51(11):875-8
references.pmid: 1008594
references.citation: Am J Med. 1987 May;82(5):945-52
references.pmid: 3578363
references.citation: Circulation. 2004 Oct 19;110(16):2342-8
references.pmid: 15477399
references.citation: Arch Gerontol Geriatr. 1999 Jul-Aug;29(1):75-94
references.pmid: 15374079
references.citation: Clin Chem. 2000 Feb;46(2):193-7
references.pmid: 10657375
references.citation: Kidney Int. 2004 Apr;65(4):1416-21
references.pmid: 15086483
references.citation: Scand J Clin Lab Invest. 2004;64(1):25-30
references.pmid: 15025426
references.citation: Clin Chem. 2000 Aug;46(8 Pt 1):1206-7
references.pmid: 10926911
references.citation: Scand J Clin Lab Invest. 1997 Oct;57(6):463-70
references.pmid: 9350064
references.citation: Clin Chim Acta. 2003 Dec;338(1-2):87-90
references.pmid: 14637271
references.citation: Am J Kidney Dis. 2006 Aug;48(2):221-30
references.pmid: 16860187
references.citation: Ann Clin Biochem. 2001 Mar;38(Pt 2):111-4
references.pmid: 11269749
references.citation: Am J Kidney Dis. 2003 Feb;41(2):269-78
references.pmid: 12552488
references.citation: Clin Chem. 1998 Dec;44(12):2556-7
references.pmid: 9836733
references.citation: Kidney Int. 2006 Jul;70(1):204-10
references.pmid: 16723983
references.citation: Clin Chem. 2007 Apr;53(4):766-72
references.pmid: 17332152
references.citation: Clin Chem. 1999 Dec;45(12):2243-9
references.pmid: 10585359
references.citation: Nephrol Dial Transplant. 1999 Aug;14(8):1991-6
references.pmid: 10462282
references.citation: Clin Chem Lab Med. 1998 Nov;36(11):859-65
references.pmid: 9877092
references.citation: Hypertension. 2003 Nov;42(5):1050-65
references.pmid: 14604997
references.citation: Scand J Clin Lab Invest. 2005;65(2):111-24
references.pmid: 16025834
references.citation: J Hypertens. 1999 Mar;17(3):309-17
references.pmid: 10100067
references.citation: Ann Clin Biochem. 2003 Jul;40(Pt 4):427
references.pmid: 12880549
references.citation: Curr Opin Nephrol Hypertens. 1998 Nov;7(6):675-80
references.pmid: 9864664
references.citation: Clin Chem. 1993 Sep;39(9):1885-90
references.pmid: 8375065
references.citation: Nephrol Dial Transplant. 2006 Mar;21(3):660-4
references.pmid: 16326735
references.citation: Ups J Med Sci. 2007;112(1):21-37
references.pmid: 17578805
references.citation: Clin Chim Acta. 2002 Feb;316(1-2):165-70
references.pmid: 11750287
references.citation: Kidney Int. 2002 Apr;61(4):1453-61
references.pmid: 11918752
references.citation: J Am Soc Nephrol. 2002 Aug;13(8):2140-4
references.pmid: 12138147
references.citation: Circulation. 2007 Jan 16;115(2):173-9
references.pmid: 17190862
references.citation: Scand J Clin Lab Invest. 1995 Nov;55(7):617-23
references.pmid: 8633186
references.citation: N Engl J Med. 2004 Sep 23;351(13):1296-305
references.pmid: 15385656
references.citation: BJOG. 2003 Sep;110(9):825-30
references.pmid: 14511964
references.citation: J Am Coll Cardiol. 2005 Jan 18;45(2):268-71
references.pmid: 15653026
references.citation: Clin Chem. 2002 May;48(5):699-707
references.pmid: 11978596
references.citation: Clin Chem. 1999 Oct;45(10):1866-8
references.pmid: 10508138
references.citation: Diabetologia. 2006 Jul;49(7):1686-9
references.pmid: 16752187
references.citation: Ann Intern Med. 2007 Jul 3;147(1):19-27
references.pmid: 17606957
references.citation: Diabetes Care. 2007 Jul;30(7):1724-9
references.pmid: 17456840
references.citation: Ann Clin Biochem. 2000 Jan;37 ( Pt 1):49-59
references.pmid: 10672373
references.citation: Am J Perinatol. 1999;16(6):287-95
references.pmid: 10586982
references.citation: Med J Aust. 2005 Aug 1;183(3):138-41
references.pmid: 16053416
references.citation: Kidney Int. 1995 Jan;47(1):312-8
references.pmid: 7731163
references.citation: Clin Chem. 2002 Jun;48(6 Pt 1):850-8
references.pmid: 12029000
references.citation: J Am Soc Nephrol. 2005 Dec;16(12):3763-70
references.pmid: 16236805
references.citation: Nephrol Dial Transplant. 2006 Dec;21(12):3614
references.pmid: 16877493
references.citation: Clin Pharmacokinet. 2005;44(12):1305-16
references.pmid: 16372828
references.citation: BMJ. 2006 Mar 11;332(7541):563-4
references.pmid: 16528062
references.citation: Ann Intern Med. 2002 Oct 1;137(7):555-62
references.pmid: 12353942
references.citation: Kidney Blood Press Res. 2006;29(1):32-5
references.pmid: 16582575
references.citation: Scand J Clin Lab Invest. 2001;61(7):575-80
references.pmid: 11763416
references.citation: Ann Clin Biochem. 2002 May;39(Pt 3):308-10
references.pmid: 12038606
references.citation: J Am Soc Nephrol. 2005 Mar;16(3):763-73
references.pmid: 15659562
references.citation: Ann Clin Biochem. 2003 Jan;40(Pt 1):60-4
references.pmid: 12542911
references.citation: Ann Intern Med. 1999 Mar 16;130(6):461-70
references.pmid: 10075613
references.citation: Clin Chim Acta. 2001 Sep 25;311(2):81-9
references.pmid: 11566167
references.citation: Kidney Int. 2003 May;63(5):1944-7
references.pmid: 12675875
references.citation: Clin Chem. 1997 Jun;43(6 Pt 1):1016-22
references.pmid: 9191555
references.citation: J Am Coll Cardiol. 2003 Jan 1;41(1):47-55
references.pmid: 12570944
references.citation: Clin Chem. 2001 Nov;47(11):2055-9
references.pmid: 11673383
references.citation: Nephrol Dial Transplant. 2004 Nov;19(11):2858-63
references.pmid: 15496561
references.citation: Biochem J. 1990 Jun 1;268(2):287-94
references.pmid: 2363674
references.citation: Scand J Clin Lab Invest. 2002;62(2):141-7
references.pmid: 12004930
references.citation: Clin Chem. 2005 Aug;51(8):1420-31
references.pmid: 15961546
references.citation: Clin Biochem. 2007 Mar;40(5-6):383-91
references.pmid: 17316593
references.citation: Pediatrics. 1998 May;101(5):875-81
references.pmid: 9565418
references.citation: Clin Chem. 2006 Jan;52(1):5-18
references.pmid: 16332993
references.citation: Crit Rev Clin Lab Sci. 2004;41(5-6):467-550
references.pmid: 15603510
references.citation: J Pediatr. 1985 Mar;106(3):522-6
references.pmid: 3973793
references.citation: Liver Transpl. 2002 Jul;8(7):594-9
references.pmid: 12089712
references.citation: Med J Aust. 2007 Oct 15;187(8):459-63
references.pmid: 17937643
references.citation: Ann Intern Med. 2006 Aug 15;145(4):247-54
references.pmid: 16908915
references.citation: Clin Chem. 2002 Jul;48(7):1123-6
references.pmid: 12089191
references.citation: Diabetes Care. 2003 Apr;26(4):1320
references.pmid: 12663624
references.citation: Ann Intern Med. 2004 Dec 21;141(12):929-37
references.pmid: 15611490
references.citation: Clin Chem. 1992 Oct;38(10):1933-53
references.pmid: 1394976
references.citation: Pediatr Nephrol. 2003 Oct;18(10):981-5
references.pmid: 12920638
references.citation: Nephrol Dial Transplant. 2006 May;21(5):1253-6
references.pmid: 16421151
references.citation: J Ren Nutr. 2001 Jul;11(3):149-54
references.pmid: 11466665
references.citation: Clin Chim Acta. 2001 Jul 5;309(1):1-6
references.pmid: 11407999
references.citation: Ann Clin Biochem. 2003 Nov;40(Pt 6):648-55
references.pmid: 14629803
references.citation: Pediatr Nephrol. 2004 Oct;19(10):1145-7
references.pmid: 15258844
references.citation: N Engl J Med. 1984 Feb 9;310(6):356-60
references.pmid: 6690964
references.citation: Clin Biochem. 2005 Jan;38(1):1-8
references.pmid: 15607309
references.citation: Clin Biochem. 2006 Feb;39(2):115-8
references.pmid: 16337174
references.citation: Arch Intern Med. 2003 Feb 10;163(3):356-60
references.pmid: 12578517
references.citation: J Am Soc Nephrol. 2003 Oct;14(10):2573-80
references.pmid: 14514734
references.citation: J Am Soc Nephrol. 2005 May;16(5):1404-12
references.pmid: 15788478
references.citation: Scand J Clin Lab Invest. 1985 Apr;45(2):97-101
references.pmid: 3923607
references.citation: J R Soc Med. 1983 Jun;76(6):485-501
references.pmid: 6345778
references.citation: J Am Soc Nephrol. 2005 Feb;16(2):459-66
references.pmid: 15615823
references.citation: Scand J Clin Lab Invest. 1996 Aug;56(5):409-14
references.pmid: 8869663
references.citation: Clin Chem. 2000 May;46(5):712-5
references.pmid: 10794756
references.citation: Ann Clin Biochem. 2003 Mar;40(Pt 2):195-6
references.pmid: 12666666
references.citation: Scand J Clin Lab Invest. 1999 Feb;59(1):1-8
references.pmid: 10206092
references.citation: Ann Intern Med. 2003 Jul 15;139(2):137-47
references.pmid: 12859163
references.citation: Nephron. 1976;16(1):31-41
references.pmid: 1244564
references.citation: Clin Chem. 2007 Dec;53(12):2219-21
references.pmid: 18267934
references.citation: N Engl J Med. 2005 May 19;352(20):2049-60
references.pmid: 15901858
references.citation: Pediatr Med Chir. 1997 Sep-Oct;19(5):325-9
references.pmid: 9493223
references.citation: Am J Kidney Dis. 2002 Aug;40(2):221-6
references.pmid: 12148093
references.citation: Transplant Proc. 2000 Dec;32(8):2779
references.pmid: 11134801
references.citation: Ann Intern Med. 2006 Aug 15;145(4):237-46
references.pmid: 16908914
references.citation: J Am Soc Nephrol. 1999 Jan;10(1):164-6
references.pmid: 9890323
references.citation: Clin Chem. 1998 Jul;44(7):1535-9
references.pmid: 9665434
references.citation: Clin Chem Lab Med. 2007;45(9):1237-9
references.pmid: 17848122
references.citation: Clin Biochem. 2007 Feb;40(3-4):153-61
references.pmid: 17234172
references.citation: Pediatr Nephrol. 1998 Feb;12(2):125-9
references.pmid: 9543370
references.citation: J Nucl Med. 1996 Nov;37(11):1883-90
references.pmid: 8917197
references.citation: Clin Chim Acta. 2000 Oct;300(1-2):83-95
references.pmid: 10958865
references.citation: Liver Transpl. 2005 Mar;11(3):344-9
references.pmid: 15719405
references.citation: J Am Soc Nephrol. 1998 Feb;9(2):310-3
references.pmid: 9527409
references.citation: Scand J Clin Lab Invest. 2007;67(5):560-7
references.pmid: 17763193
references.citation: Liver Transpl. 2006 Feb;12(2):285-91
references.pmid: 16447198
references.citation: Ann Intern Med. 2005 Apr 5;142(7):497-505
references.pmid: 15809461
references.citation: Kidney Int. 2006 Jan;69(2):399-405
references.pmid: 16408133
references.citation: Nephrol Dial Transplant. 2003 Oct;18(10):2024-31
references.pmid: 13679476
references.citation: Diabet Med. 2007 Apr;24(4):443-8
references.pmid: 17388960
references.citation: Scand J Clin Lab Invest. 2007;67(8):801-9
references.pmid: 17852801
references.citation: Pediatr Nephrol. 2006 Sep;21(9):1299-306
references.pmid: 16794818
references.citation: Clin Chem. 1994 Oct;40(10):1921-6
references.pmid: 7923773
references.citation: Clin Chem. 2002 May;48(5):729-36
references.pmid: 11978599
references.citation: Ann Intern Med. 2006 Feb 7;144(3):172-80
references.pmid: 16461961
references.citation: Arch Dis Child. 2000 Jan;82(1):71-5
references.pmid: 10630919
references.citation: Clin Chem. 2001 Nov;47(11):2031-3
references.pmid: 11673373
references.citation: Ann Clin Biochem. 2002 Mar;39(Pt 2):89-104
references.pmid: 11928770
references.citation: Nephrol Dial Transplant. 2002 Nov;17(11):1909-13
references.pmid: 12401845
references.citation: J Am Soc Nephrol. 1996 Apr;7(4):567-72
references.pmid: 8724890
references.citation: Pediatr Nephrol. 2000 Nov;15(1-2):105-8
references.pmid: 11095024
references.citation: Circulation. 2003 Oct 28;108(17):2154-69
references.pmid: 14581387