Filtration markers as predictors of ESRD and mortality: Individual participant data meta-analysis

Lesley A. Inker, Josef Coresh, Yingying Sang, Chi Yuan Hsu, Meredith C. Foster, John H. Eckfeldt, Amy B. Karger, Robert G. Nelson, Xun Liu, Mark Sarnak, Lawrence J. Appel, Morgan Grams, Dawei Xie, Paul L. Kimmel, Harold Feldman, Vasan Ramachandran, Andrew S. Levey, The CKD Biomarkers Consortium

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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) andB2M(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.

Original languageEnglish (US)
Pages (from-to)69-78
Number of pages10
JournalClinical Journal of the American Society of Nephrology
Volume12
Issue number1
DOIs
StatePublished - Jan 6 2017

Bibliographical note

Funding Information:
The authors thank the staff and participants of the Atherosclerosis Risk in Communities (ARIC) Study for their important contributions. Reagents for b-2-microglobulin at the ARIC visit 2 were donated by Roche Diagnostics. The CKD Biomarkers Consortium is funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants U01DK85649, U01DK085673, U01DK085660, U01DK085688, U01DK085651, and U01DK085689, and by the Intramural Research Program of the NIDDK. M.C.F. was supported in part by National Heart, Lung and Blood Institute grant T32HL007024. Funding for the Chronic Renal Insufficiency Cohort (CRIC) Study was obtained under a cooperative agreement from the NIDDK (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this workwas supported in part by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland General Clinical Research Center (GCRC) M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences component of the NIH and the NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1TR000433, University of Illinois at Chicago Center for Clinical and Translational Science (CTSA) UL1RR029879,Tulane University Translational Research in Hypertension and Renal Biology P30GM103337, Kaiser Permanente NIH/National Center for Research Resources (NCRR) University of California- San Francisco Clinical and Translational Science Institute (UCSF CTSI) UL1RR024131. The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Funding for cystatinCmeasurementswere supported by NIH/NIDDK grant R01DK089174 to Dr.Elizabeth Selvin. Some of the data reported here have been supplied by the United States Renal Data System. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the United States government.

Publisher Copyright:
© 2016 by the American Society of Nephrology.

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

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