Glomerular Filtration Rate Estimation Using β2-Microglobulin and β-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study

Abstract

Rationale & objective: β₂-Microglobulin (B2M) and β-trace protein (BTP) are novel endogenous filtration markers that may improve the accuracy of estimated glomerular filtration rate (eGFR) beyond creatinine and cystatin C (eGFR_cr-cys), but they have not been assessed in patients with cancer.

Study design: Cross-sectional analysis.

Setting & participants: Prospective cohort of 1,200 patients with active solid tumors recruited between April 2015 and September 2017.

Exposure: CKD-EPI equations without race combining B2M and/or BTP with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR).

Outcome: Performance of equations compared with eGFR_cr-cys and non-GFR determinants of serum B2M and BTP (S_B2M, and S_BTP, respectively). Measured GFR (mGFR) was determined using the plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (⁵¹Cr-EDTA).

Analytical approach: Bias was defined as the median of the differences between mGFR and eGFR, and 1-P₃₀ was defined as the percentage of estimates that differed by more than 30% from the mGFR (1-P₃₀). Linear regression was used to assess association of clinical and laboratory variables with S_B2M, and S_BTP after adjustment for mGFR.

Results: Mean age and mGFR were 58.8±13.2 SD years and 78.4±21.7 SD mL/min/1.73m², respectively. Performance of the 3-marker and 4-marker panel equations was better than eGFR_cr-cys (lesser bias and 1-P₃₀). Performance of 2-marker panel equations was as good as eGFR_cr-cys (lesser bias and similar 1-P₃₀). S_B2M and S_BTP were not strongly influenced by cancer site.

Limitations: Participants may have had better clinical performance status than the general population of patients with solid tumors.

Conclusions: B2M and BTP can improve the accuracy of eGFR and may be useful as confirmatory tests in patients with solid tumors, either by inclusion in a multimarker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine.

Plain-language summary: The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFR_cr-cys). We studied whether using β2-microglobulin (B2M) and/or β-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFR_cr-cys. Performance of 2-marker panel equations was as good as eGFR_cr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

Keywords: cancer patients; estimating equations; glomerular filtration rate; β(2)-Microglobulin; β-trace protein.