Estimation of GFR Using β-Trace Protein in Children

Abstract

Background and objectives Sex may affect the performance of small molecular weight proteins as markers of GFR because of differences in fat mass between the two sexes. The hypothesis was that the diagnostic performance of b-trace protein, a novel marker of GFR, would be significantly better in boys than in girls.Design, setting, participants, & measurements GFR, height, weight, serum creatinine, and b-trace protein were measured in 755 children and adolescents (331 girls) undergoing 99 technetium diethylenetriamine penta-acetic acid renal scans from July of 1999 to July of 2006. Boys and girls were separated into formula generation cohorts (284 boys and 220 girls) and formula validation cohorts (140 boys and 111 girls). GFRestimating formulas on the basis of b-trace protein, creatinine, and height were derived using stepwise linear regression analysis of log-transformed data. The slope of the regression lines of the sex-specific eGFRs were compared. Bland-Altman analysis was used for testing agreement between 99 technetium diethylenetriamine penta-acetic acid GFR and calculated GFR both with this equation in boys and girls as well as previously established Benlamri, White, and Schwartz formulas. ResultsIn the stepwise regression analysis, b-trace protein (R 2 =0.73 for boys and R 2 =0.65 for girls) was more important than creatinine (which increased R 2 to 0.81 for boys and R 2 to 0.75 for girls) and height (which increased R 2 to 0.88 for boys and R 2 to 0.80 for girls) in the data generation groups. GFR can be calculated using the following formulas: Bland-Altman analysis showed better performance in boys than in girls. The new formulas performed significantly better than the previous Benlamri, White, and Schwartz formulas with respect to bias, precision, and accuracy.Conclusions Improved and sex-specific formulas for the estimation of GFR in children on the basis of b-trace protein, serum creatinine, and height are now available.

Can the new CKD-EPI BTP-B2M formula be applied in children?

“…The volume of distribution of cystatin C is most likely the extracellular volume (ECV), which correlates better with lean body mass than body surface area [9]. While BTP is produced in the coronary arteries (reviewed recently by Filler et al [10], the differing fat mass between the genders has been shown to affect BTP-based GFR estimates [2]. Its volume of distribution is unknown [10].…”

“…We were particularly interested in the fact that there was no bias induced by gender. There is a significant difference in body fat between the genders during puberty [2]. An adjustment for gender must be made in order to accurately estimate GFR in children when using creatinine [2,3], cystatin C [4], and BTP [2,5].…”

Spot urine protein to creatinine ratio

“…EM Yang et al [4] used the entire cohort to generate the formula. The authors could have divided their study participants into one cohort of 160 patients to generate the formula and a second cohort composed of the remaining patients to validate the formula, akin to other biomarker discovery studies [13,14]. There are five stages for biomarker development, and the later stages focus on epidemiologic concepts within a diagnostic, prognostic, and screening framework to determine if new markers will advance clinical care [15].…”

The Search for More Reliable Estimated GFR Biomarkers

“…The impact of sex confirms our previous findings. 37,38 For B2M, there was no effect of sex, and the equation based on BTP and B2M was free of significant bias. Not unexpectedly, this study demonstrates that age, sex, and race are less influential for both these small-molecular-weight proteins in comparison to creatinine, but not cystatin C. Most importantly, the authors demonstrated that the coefficient of variation of B2M for sex was smaller than that of cystatin C, which is probably due to the increased fat mass of women because adipocytes are the only nucleated cells in the body that do not produce cystatin C. 24 The authors then combined B2M and BTP and the resultant formula had similar accuracy to the CKD-EPI creatinine-cystatin C equation.…”

“…Currently, BTP measurement is generally used for the detection of cerebrospinal fluid leakage, 36 and only a few laboratories routinely offer serum BTP for the assessment of eGFR. 36,37,39 In addition, it is likely that each biomarker will have some populations in which it is particularly well or poorly suited. Both BTM and B2M appear to have some advantages over serum creatinine for GFR estimation, but systemic inflammation and other factors clearly have some influence on the production of small-molecular-weight proteins, making the utility of these novel biomarkers less certain in people with acute and chronic systemic inflammatory states.…”