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Novel markers of kidney function as predictors of ESRD, cardiovascular disease, and mortality in the general population.

TitleNovel markers of kidney function as predictors of ESRD, cardiovascular disease, and mortality in the general population.
Publication TypeJournal Article
Year of Publication2012
AuthorsAstor BC, Shafi T, Hoogeveen RC, Matsushita K, Ballantyne CM, Inker LA
Secondary AuthorsCoresh JJ
JournalAm J Kidney Dis
Volume59
Issue5
Pagination653-62
Date Published2012 May
ISSN1523-6838
KeywordsAged, beta 2-Microglobulin, Biomarkers, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Creatinine, Cystatin C, Female, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Intramolecular Oxidoreductases, Kidney, Kidney Failure, Chronic, Lipocalins, Longitudinal Studies, Male, Middle Aged, Outcome Assessment, Health Care, Predictive Value of Tests, Risk Factors
Abstract

BACKGROUND: Cystatin C level predicts mortality more strongly than serum creatinine level. It is unknown whether this advantage extends to other outcomes, such as kidney failure, or whether other novel renal filtration markers share this advantage in predicting outcomes.

STUDY DESIGN: Observational cohort study.

SETTING & PARTICIPANTS: 9,988 participants in the Atherosclerosis Risk in Communities (ARIC) Study, a population-based study in 4 US communities, followed for approximately 10 years.

PREDICTORS: Serum creatinine-based estimated glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFR(CKD-EPI)) and cystatin C, β-trace protein (BTP), and β(2)-microglobulin (B2M) levels.

OUTCOMES: Mortality, coronary heart disease, heart failure, and kidney failure.

RESULTS: Higher cystatin C and B2M concentrations were associated more strongly with mortality (n = 1,425) than BTP level and all were associated more strongly than eGFR(CKD-EPI) (adjusted HR for the upper 6.7 percentile compared with the lowest quintile: 1.6 [95% CI, 1.3-1.9] for eGFR(CKD-EPI), 2.9 [95% CI, 2.3-3.6] for cystatin C level, 1.9 [95% CI, 1.5-2.4] for BTP level, and 3.0 [95% CI, 2.4-3.8] for B2M level). Similar patterns were observed for coronary heart disease (n = 1,279), heart failure (n = 803), and kidney failure (n = 130). The addition of cystatin C, BTP, and B2M levels to models including eGFR(CKD-EPI) and all covariates, including urinary albumin-creatinine ratio, significantly improved risk prediction for all outcomes (P

LIMITATIONS: No direct measurement of GFR.

CONCLUSIONS: B2M and, to a lesser extent, BTP levels share cystatin C's advantage over eGFR(CKD-EPI) in predicting outcomes, including kidney failure. These additional markers may be helpful in improving estimation of risk associated with decreased kidney function beyond current estimates based on eGFR(CKD-EPI).

DOI10.1053/j.ajkd.2011.11.042
Alternate JournalAm J Kidney Dis
PubMed ID22305758
PubMed Central IDPMC3880682
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N01 HC055022 / HC / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
K23 DK083514 / DK / NIDDK NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
1 R01 DK076770-01 / DK / NIDDK NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
R01 DK076770 / DK / NIDDK NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
U01 DK085689 / DK / NIDDK NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01 HC055020 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States