Filtration Markers as Predictors of ESRD and Mortality: Individual Participant Data Meta-Analysis

Clin J Am Soc Nephrol. 2017 Jan 6;12(1):69-78. doi: 10.2215/CJN.03660316. Epub 2016 Nov 10.


Background and objectives: Serum β-trace protein (BTP) and β-2 microglobulin (B2M) are associated with risk of ESRD and death in the general population and in populations at high risk for these outcomes (GP/HR) and those with CKD, but results differ among studies.

Design, setting, participants, & measurements: We performed an individual patient-level meta-analysis including three GP/HR studies (n=17,903 participants) and three CKD studies (n=5415). We compared associations, risk prediction, and improvement in reclassification of eGFR using BTP (eGFRBTP) and B2M (eGFRB2M) alone and the average (eGFRavg) of eGFRBTP, eGFRB2M, creatinine (eGFRcr), and cystatin C (eGFRcys), to eGFRcr, eGFRcys, and their combination (eGFRcr-cys) for ESRD (2075 events) and death (7275 events).

Results: Mean (SD) follow up times for ESRD and mortality for GP/HR and CKD studies were 13 (4), 6.2 (3.2), 14 (5), and 7.5 (3.9) years, respectively. Compared with eGFRcr, eGFRBTP and eGFRB2M improved risk associations and modestly improved prediction for ESRD and death even after adjustment for established risk factors. eGFRavg provided the most consistent improvement in associations and prediction across both outcomes and populations. Assessment of heterogeneity did not yield clinically relevant differences. For ESRD, addition of albuminuria substantially attenuated the improvement in risk prediction and risk classification with novel filtration markers. For mortality, addition of albuminuria did not affect the improvement in risk prediction with the use of novel markers, but lessened improvement in risk classification, especially for the CKD cohort.

Conclusions: These markers do not provide substantial additional prognostic information to eGFRcr and albuminuria, but may be appropriate in circumstances where eGFRcr is not accurate or albuminuria is not available. Educational efforts to increase measurement of albuminuria in clinical practice may be more cost-effective than measurement of BTP and B2M for improving prognostic information.

Keywords: albuminuria; beta 2-microglobulin; chronic kidney disease; follow-up studies; glomerular filtration rate; humans; intramolecular oxidoreductases; kidney failure, chronic; lipocalins; prostaglandin R2 D-isomerase; renal insufficiency, chronic; risk factors.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Albuminuria / urine
  • Biomarkers / blood
  • Creatinine / blood
  • Cystatin C / blood
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate*
  • Humans
  • Intramolecular Oxidoreductases / blood*
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / epidemiology*
  • Kidney Failure, Chronic / physiopathology
  • Lipocalins / blood*
  • Male
  • Middle Aged
  • Mortality*
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • beta 2-Microglobulin / blood*


  • Biomarkers
  • Cystatin C
  • Lipocalins
  • beta 2-Microglobulin
  • Creatinine
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase

Grant support