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

TitleFiltration Markers as Predictors of ESRD and Mortality: Individual Participant Data Meta-Analysis.
Publication TypeJournal Article
Year of Publication2017
AuthorsInker LA, Coresh JJ, Sang Y, Hsu C-Y, Foster MC, Eckfeldt JH, Karger AB, Nelson RG, Liu X, Sarnak M, Appel LJ, Grams M, Xie D, Kimmel PL, Feldman H, Ramachandran V
Secondary AuthorsLevey AS
Corporate AuthorsCKD Biomarkers Consortium
JournalClin J Am Soc Nephrol
Volume12
Issue1
Pagination69-78
Date Published2017 01 06
ISSN1555-905X
KeywordsAdult, Aged, Albuminuria, beta 2-Microglobulin, Biomarkers, Creatinine, Cystatin C, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Intramolecular Oxidoreductases, Kidney Failure, Chronic, Lipocalins, Male, Middle Aged, Mortality, Predictive Value of Tests, Risk Assessment, Risk Factors
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 (eGFR) and B2M (eGFR) alone and the average (eGFR) of eGFR, eGFR, creatinine (eGFR), and cystatin C (eGFR), to eGFR, eGFR, and their combination (eGFR) 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 eGFR, eGFR and eGFR improved risk associations and modestly improved prediction for ESRD and death even after adjustment for established risk factors. eGFR 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 eGFR and albuminuria, but may be appropriate in circumstances where eGFR 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.

DOI10.2215/CJN.03660316
Alternate JournalClin J Am Soc Nephrol
PubMed ID28062677
PubMed Central IDPMC5220652
Grant ListU01 DK061028 / DK / NIDDK NIH HHS / United States
UL1 TR000433 / TR / NCATS NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
U01 DK085660 / DK / NIDDK NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 DK060984 / DK / NIDDK NIH HHS / United States
U01 DK061021 / DK / NIDDK NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
UL1 TR001878 / TR / NCATS NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
P30 GM103337 / GM / NIGMS NIH HHS / United States
U01 DK060980 / DK / NIDDK NIH HHS / United States
U01 DK060963 / DK / NIDDK NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
T32 HL007024 / HL / NHLBI NIH HHS / United States
U01 DK085673 / DK / NIDDK NIH HHS / United States
UL1 RR024131 / RR / NCRR NIH HHS / United States
U01 DK085651 / DK / NIDDK NIH HHS / United States
U01 DK061022 / DK / NIDDK NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
UL1 TR000003 / TR / NCATS NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
U01 DK085649 / DK / NIDDK NIH HHS / United States
UL1 TR000439 / TR / NCATS NIH HHS / United States
UL1 TR000424 / TR / NCATS NIH HHS / United States
M01 RR016500 / RR / NCRR NIH HHS / United States
U01 DK060902 / DK / NIDDK NIH HHS / United States
U01 DK085689 / DK / NIDDK NIH HHS / United States
U01 DK060990 / DK / NIDDK NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
U01 DK085688 / DK / NIDDK NIH HHS / United States
UL1 RR029879 / RR / NCRR NIH HHS / United States