NDT Advance Access originally published online on July 28, 2006
Nephrology Dialysis Transplantation 2006 21(12):3614; doi:10.1093/ndt/gfl453
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Utility of cystatin C measurement—precision or secretion?
Email: jix{at}medicine.ucsf.eduSir,
Recently, van Rossum and colleagues [1] evaluated the renal extraction of cystatin C compared with 125I-iothalamate in 40 patients with unilateral renal artery stenosis. The authors reported that the mean difference between these two measures of glomerular filtration rate was small (0.002); however the limits of agreement by Bland and Altman technique [2] were quite large (–0.271 to 0.267). The authors concluded that this difference may reflect previously unrecognized tubular secretion of cystatin C and that cystatin C may not be a useful endogenous measure of kidney function.
The cystatin C assay employed by van Rossum and colleagues [1] uses a turbinometric immunoassay which has relatively poor intra-assay precision [3]. Using their controls, the authors report an intra-assay coefficient variation of 11%, substantially greater than that for creatinine [1]. The authors repeated cystatin C measurements in triplicate. Whereas this may improve the precision of the mean value, it would do little to improve the variation between measurements. Cystatin C is freely filtered at the glomerulus [4], more than 99% is catabolized by proximal tubular cells [5], and the urinary concentration of cystatin C is very low under normal physiological conditions [6]. Perhaps the imprecision in measurement of cystatin C led to the larger limits of agreement, rather than previously unrecognized renal tubular secretion. A nephelometric assay that has lower coefficients of variation is commercially available [7]. Would the results have been similar with this assay?
Despite its limitations, creatinine measurement is precise, readily available, and inexpensive. Cystatin C may eventually prove useful in clinical situations where serum creatinine concentrations might erroneously mislead clinicians to believe that the glomerular filtration rate is normal, rather than as a universal replacement of serum creatinine and associated derived estimating equations. Examples where cystatin C measurement might prove most useful include evaluation of kidney function among persons with advanced age [8] and low muscle mass [8,9], and among persons with normal or near-normal glomerular filtration rate [10].
Conflict of interest statement. None declared.
Division of Nephrology
Department of Medicine
Box 0532, HSE 672
University of California, San Francisco
San Francisco, CA 94143-0532
USA
References
- van Rossum LK, Zietse R, Vulto AG, de Rijke YB. (2006) Renal extraction of cystatin C vs 125I-iothalamate in hypertensive patients. Nephrol Dial Transplant 21:1253–1256.
[Abstract/Free Full Text] - Bland JM and Altman DG. (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310.[CrossRef][ISI][Medline]
- Lewis AV, James TJ, McGuire JB, Taylor RP. (2001) Improved immunoturbidimetric assay for cystatin C. Ann Clin Biochem 38:Pt 2111–114.[CrossRef][ISI][Medline]
- Bianchi C, Donadio C, Tramonti G, et al. (1988) Renal handling of cationic and anionic small proteins: experiments in intact rats. Contrib Nephrol 68:37–44.[Medline]
- Thakkar H, Lowe PA, Price CP, Newman DJ. (1998) Measurement of the kinetics of protein uptake by proximal tubular cells using an optical biosensor. Kidney Int 54:1197–1205.[CrossRef][ISI][Medline]
- Lofberg H and Grubb AO. (1979) Quantitation of gamma-trace in human biological fluids: indications for production in the central nervous system. Scand J Clin Lab Invest 39:619–626.[ISI][Medline]
- Erlandsen EJ, Randers E, Kristensen JH. (1999) Evaluation of the Dade Behring N Latex Cystatin C assay on the Dade Behring Nephelometer II System. Scand J Clin Lab Invest 59:1–8.[CrossRef][ISI][Medline]
- Uchida K and Gotoh A. ( Sep 2002) Measurement of cystatin-C and creatinine in urine. Clin Chim Acta 323:121–128.[CrossRef][ISI][Medline]
- Bokenkamp A, Domanetzki M, Zinck R, Schumann G, Byrd D, Brodehl J. (1998) Cystatin C—a new marker of glomerular filtration rate in children independent of age and height. Pediatrics 101:875–881.
[Abstract/Free Full Text] - Perkins BA, Nelson RG, Ostrander BE, et al. (2005) 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 16:1404–1412.
[Abstract/Free Full Text]
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