Clinical Chemistry
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Clinical Chemistry 51: 2211-2212, 2005; 10.1373/clinchem.2005.057075
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(Clinical Chemistry. 2005;51:2211-2212.)
© 2005 American Association for Clinical Chemistry, Inc.


Letters to the Editor

Differences in Glomerular Filtration Rate Estimates by 2 Cystatin C–Based Equations

Lorenz Risch1, Heinz Drexel2 and Andreas R. Huber3,a

1 Clinical Decision-Making Research Unit, Vorarlberg Institute of Vascular Investigation and Treatment, and2 Department of Internal Medicine, Academic Teaching Hospital, Feldkirch, Austria
3 Department of Laboratory Medicine, Kantonsspital, Aarau, Switzerland

aAddress correspondence to this author at: Department of Laboratory Medicine, Kantonsspital, 5001 Aarau, Switzerland. Fax 41-62-838-53-99; e-mail andreas.huber{at}ksa.ch.


To the Editor:

Glomerular filtration rate (GFR) represents the best overall index of kidney function (1), and the National Kidney Foundation has recommended that clinical laboratories routinely report an estimate of GFR(1)(2). Several cystatin C–based equations for calculation of GFR have been reported(3)(4). The most recent equations have been published by Larsson et al. (GFRLarsson = 99.43 x cystatin C–1.5837)(4) and Grubb et al. [GFRGrubb = 84.69 x cystatin C–1.680 (x 0.948 if female)](5).

Both groups report on GFR estimates obtained from particle-enhanced turbidimetric immunoassay measurements of cystatin C (DakoCytomation). After correcting the Larsson estimate for body surface according to the Du Bois and Du Bois formula (6), we compared both equations, using data from 29 adult renal transplant patients who also had undergone 125I-iothalamate clearance determination as a reference measurement of GFR(7)(8). For cystatin C measurements, we used a particle-enhanced turbidimetric immunoassay (Dako) run on a Cobas Mira instrument (Roche Diagnostics), as described earlier(7)(8).

The correlation of the Larsson and Grubb cystatin C-based GFR estimates was highly significant (r = 0.98; P <0.001); however, evaluation of these methods by linear regression showed a slope substantially different from 1, indicating 23% higher GFR values obtained with the Larsson estimate (Fig. 1 ). The Larsson estimates were substantially higher than the Grubb estimates even when adjustment for body surface area was not performed (data not shown).



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Figure 1. Cystatin C–based estimates of GFR calculated according to the equations of Larsson et al. (4) and Grubb et al.(5).

The equation of the linear regression line (dashed) is GFRLarsson [mL · min–1 · (1.73m2)–1] = 1.23 (0.046) x GFRGrubb + 2.19 (1.59). The solid diagonal line indicates equal GFR estimates.

In comparison with the 125I-iothalamate clearance, the linear regression line for the Grubb estimate was (numbers in parentheses are the SD):

whereas the linear regression line for the Larsson estimate adjusted for body surface area was:

When we compared the slopes and intercepts of these 2 linear regression lines by the method described by Zar (9), a method equivalent to analysis of covariance, the 2 regression lines showed significantly different intercepts (P <0.001), whereas we found no significant difference between the slopes (P = 0.23; GraphPad Prism 4 Software). These data are consistent with 2 distinct but parallel regression lines.

The reasons for these differences remain unclear. A possible explanation may be a reformulation of the cystatin C assay (10). Other reasons might include the different procedures to evaluate the equations and the fact that our patients are different from the patient populations in which the equations were evaluated. Standardization of cystatin C assays will lead to better comparability of cystatin C–based GFR estimates. Efforts to establish an IFCC working group focused on standardization of cystatin C measurements have already been initiated. However, standardization of measurements should also evoke consensus recommendations for the use of cystatin C–based prediction equations for GFR. In the meantime, clinical laboratories will need to carefully evaluate cystatin C– and creatinine-based equations for the estimation of GFR before introducing them into routine clinical use.


References

  1. . National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(Suppl 1):S1-S246.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  2. . European best practice guidelines expert group on hemodialysis, European Renal Association. Section I. Measurement of renal function, when to refer and when to start dialysis. Nephrol Dial Transplant 2002;17(Suppl 7):7-15.[Free Full Text]
  3. Hoek FJ, Kemperman FAW, Krediet RT. A comparison between cystatin C, plasma creatinine, and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant 2003;18:2024-2031.[Abstract/Free Full Text]
  4. Larsson A, Malm J, Grubb A, Hansson LO. Calculation of glomerular filtration rate expressed in ml/min from plasma cystatin C values in mg/L. Scand J Clin Lab Invest 2004;64:25-30.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  5. Grubb A, Nymann U, Bjork J, Lindstrom V, Rippe B, Sterner G, et al. Simple cystatin C-based prediction equations for glomerular filtration rate compared with the Modification of Diet in Renal Disease prediction equation for adults and the Schwartz and the Counahan–Barratt prediction equations for children. Clin Chem 2005;51:1420-1431.[Abstract/Free Full Text]
  6. Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight are known. Arch Intern Med 1916;17:863-871.[Web of Science]
  7. Risch L, Blumberg A, Huber A. Rapid and accurate assessment of glomerular filtration rate in patients with renal transplants using cystatin C. Nephrol Dial Transplant 1999;14:1991-1996.[Abstract/Free Full Text]
  8. Risch L, Huber AR. Assessing glomerular filtration rate in renal transplant recipients by estimates derived from serum measurements of creatinine and cystatin C. Clin Chim Acta 2005;356:204-211.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  9. Zar JH. Comparing simple linear regression equations. Zar JH eds. Biostatistical analysis, 4th ed 1999:360-376 Prentice Hall Upper Saddle River, NJ. .
  10. Mussap M, Plebani M. Biochemistry and clinical role of cystatin C. Crit Rev Clin Lab Sci 2004;41:467-550.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]




This Article
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