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Estimation of glomerular filtration rate by use of beta-trace protein.

To the Editor:

Because we recently introduced beta-trace protein (BTP) for estimating glomerular filtration rate (GFR) in patients after kidney transplantation (1), we read with interest the report by White and coworkers (2). These authors proposed a BTP-based equation to calculate GFR in renal transplant recipients. Because a separate second cohort was not available in the reported study, a validation of the BTP-based formula was not performed. However, we were able to validate the suggested equation in 85 kidney transplant recipient patients who had participated in our study mentioned above.


The following equation of White and coworkers was applied:

GFR (mL/min/1.73[m.sup.2])

= 167.8 X [BTP.sup.-0,758]

X [creatinine.sup.-0.204] X 0.871

if the patient is female,

where BTP is given in milligrams per liter and creatinine is given in micromoles per liter. The computed results were compared to the reexpressed Modification of Diet in Renal Disease (MDRD) formula by determining correlation, bias, precision, and accuracy. As outlined in a previous report by White and coworkers, their creatinine is calibrated to the Cleveland Clinic laboratory (3). Thus, to provide comparability, we converted our isotopedilution mass spectrometry--calibrated creatinine to the Cleveland Clinical Laboratory using an equation proposed by Levey et al. (4). GFR was determined by technetium-diethylenetriamine pentaacetic acid clearance performed as a single-injection technique with a 2-point sampling approach at 1 and 3 h after intravenous injection, according to the method of Russell et al. (5). The mean GFR of the cohort was 38.6 (95% Cl, 35.3-41.9) mL/min/1.73 [m.sup.2] .

Correlation coefficients of the predicted GFRs by both formulae with the measured reference GFRs were high and did not differ significantly (BTP formula, r = 0.866 vs MDRD equation, r = 0.863). Both equations overestimated measured GFR to a small but significant extent [mean GFR estimated by the BTP formula was 46.7 (95% Cl, 43.0-50.4) mL/min/1.73 [m.sup.2] VS the mean GFR estimated by the MDRD equation, which was 45.3 (95% Cl, 41.1-49.6) mL/min/1.73 [m.sup.2] ; P < 0.001 for both]. The bias of the MDRD equation was somewhat lower than that of the BTP formula (6.7 vs 8.1 mL/min/1.73 [m.sup.2], not significant). Precision (measured as SD of the mean difference between measured and estimated GFR) (6) tended to be better for the BTP formula (8.44 vs 10.03 mL/min/1.73 [m.sup.2]), but this difference in precision did not quite reach statistical significance (P = 0.058). The rates of predicted GFRs within 10%, 30%, and 50% of the measured GFR were comparable (BTP formula: 24.7%,63.5%, and 84.7%, respectively, vs MDRD equation: 24.7%, 71.8%, 87.1%; not significant by McNemar test). Bland and Altman plots of the measured vs predicted GFRs of both equations are given in Fig. 1.

In conclusion, this external validation provides evidence that the performance of the BTP formula suggested by White and coworkers (2) is comparable to that of the reexpressed MDRD equation. Nevertheless, some difficulties were associated with the validation process and may have affected our results: (a) the validation cohort was relatively small, (b) although the same BTP determination technique was used, no international standardization was available, (c) differences in methods used for creatinine determination were corrected mathematically but no samples were sent to the Cleveland Clinical Laboratory for analysis, and (d) the cohorts appeared to have different degrees of graft function [mean (SD) GFR 59 (23) in the patient cohort of White vs 38.6 (15.1) in our patient cohort].

Finally, an additional economic aspect must also be taken into account: BTP is considerably more expensive than creatinine. Thus, the suggested BTP-based equation for GFR calculation will gain public recognition only when its perfomance is demonstrated to be clearly superior to the MDRD equation. Further studies are needed to elucidate this issue more clearly.

Grant/Funding Support: None declared.

Financial Disclosures: None declared. References

(1.) Poge U, Gerhardt TM, Stoffel-Wagner B, Palmedo H, Klehr HU, Sauerbruch T, Woitas RP. Beta-trace protein is an alternative marker for glomerular filtration rate in renal transplantation patients. Clin Chem 2005;51:1531-3.

(2.) White CA, Akbari A, Doucette S, Fergusson D, Hussain N, Dinh L, et al. A novel equation to estimate glomerular filtration rate using beta-trace protein. Clin Chem 2007;53:1965-8.

(3.) White C, Akbari A, Hussain N, Dinh L, Filler G, Lepage N, Knoll GA. Estimating glomerular filtration rate in kidney transplantation: a comparison between serum creatinine and cystatin C-based methods. J Am Soc Nephrol 2005;16: 3763-70.

(4.) Levey AS, Coresh J, Green@ T, Stevens LA, Zhang YL, Hendriksen S, et al. Using standardized serum creatinine values in the Modification of Diet in Renal Disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145:247-54.

(5.) Russell CD, Bischoff PG, Kontzen FN, Rowell KL, Yester MV, Lloyd LK, et al. Measurement of glomerularfiltration rate: single injection plasma clearance method without urine collection. J Nucl Med 1985;26:1243-7.

(6.) National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:51-5266.

Uwe Poge *

Thomas Gerhardt

Rainer P. Woitas

Department of Medicine University of Bonn, Germany

* Address correspondence to this author at: Department of Internal Medicine I University of Bonn Sigmund-Freud-Straae 25 D 53105 Bonn, Germany

Fax +49-228-2871-4952


DOI: 10.1373/clinchem.2007.101840
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Title Annotation:Letters to the Editor
Author:Poge, Uwe; Gerhardt, Thomas; Woitas, Rainer P.
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:Aug 1, 2008
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