TY - JOUR
T1 - Urine kidney injury biomarkers and risks of cardiovascular disease events and All-Cause death
T2 - The CRIC study
AU - Park, Meyeon
AU - Hsu, Chi Yuan
AU - Go, Alan S.
AU - Feldman, Harold I.
AU - Xie, Dawei
AU - Zhang, Xiaoming
AU - Mifflin, Theodore
AU - Waikar, Sushrut S.
AU - Sabbisetti, Venkata S.
AU - Bonventre, Joseph V.
AU - Coresh, Josef
AU - Nelson, Robert G.
AU - Kimmel, Paul L.
AU - Kusek, John W.
AU - Rahman, Mahboob
AU - Schelling, Jeffrey R.
AU - Vasan, Ramachandran S.
AU - Liu, Kathleen D.
N1 - Funding Information:
We thank Abbott Laboratories for supporting the measurement of urinary NGAL and CMIC for providing control materials for our studies. We also thank E. Cotter at University College Dublin, Dublin, Ireland for performing the urinary NGAL assays. This work was supported by the CKD Biomarker Consortium funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants U01DK85649, U01DK085660, and U01DK085689, and by the Intramural Research Program of the NIDDK. Funding for the Chronic Renal Insufficiency Cohort (CRIC) Study was obtained under a cooperative agreement from the NIDDK (grants U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by the following: 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) grant UL1TR000003; Johns Hopkins University grant UL1 TR-000424; University of Maryland General Clinical Research Center grant M01 RR-16500; the Clinical and Translational Science Collaborative of Cleveland, grant UL1TR000439 from the NCATS component of the NIH and NIH roadmap for Medical Research; Michigan Institute for Clinical and Health Research grant UL1TR000433; University of Illinois at Chicago Clinical and Translational Science award UL1RR029879; Tulane University Translational Research in Hypertension and Renal Biology grant P30GM103337; and Kaiser Permanente NIH/National Center for Research Resources University of California, San Francisco Clinical and Translational Science Institute grant UL1 RR-024131. M.P. is supported by NIH NIDDK grant K23 DK099238. A portion of this work was presented at the American Society of Nephrology Annual Meeting in San Diego, CA, November 5, 2015 [TH-OR121, TH-PO228]. Abbott Laboratories and CMIC had no role in study design, data collection, data analysis, data interpretation orwriting of the report. CRIC Study Investigators also include Lawrence J. Appel (Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland), Jiang He (Departments of Medicine and Epidemiology, Tulane University, New Orleans, Louisiana), James P. Lash (Section of Nephrology, Department of Medicine, University of Illinois at Chicago, Chicago, IL), Akinlolu Ojo (Department of Medicine, University of Michigan, Ann Arbor, Michigan), and Raymond R. Townsend (Department of Medicine and Center Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania).
Publisher Copyright:
© 2017 by the American Society of Nephrology.
PY - 2017
Y1 - 2017
N2 - Background and objectives CKD is an important risk factor for cardiovascular disease (CVD) and death. We investigatedwhether select urine kidney injury biomarkerswere associatedwith higher risk of heart failure (HF), CVD, and death in persons with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Design, setting, participants, & measurements Urine kidney injury molecule-1 (KIM-1), neutrophil gelatinaseassociated lipocalin, liver fatty acid-binding protein, and N-acetyl-β-D-glucosaminidase were measured in urine of a subset of CRIC participants (n=2466).We used Cox proportional hazards regression to examine associations between these biomarkers indexed to urinary creatinine (Cr) and (1) HF, (2) a composite of atherosclerotic CVD events (myocardial infarction, ischemic stroke, or peripheral artery disease), and (3) all-cause death. Results At baseline, mean age of study participants was 59.5±10.8 years, 46% were women, and 34% had a selfreported history of any CVD. Median follow-up was 6.5 (interquartile range, 5.6-6.8) years. A total of 333 HF events, 282 atherosclerotic CVD events, and 440 deaths were observed during a median follow-up of 6.5 (interquartile range, 5.6-6.8) years. Those in the highest two quintiles of KIM-1/Cr levels had a higher risk of HF relative to the lowest quintile (quintile 5 versus quintile 1 adjusted hazard ratio [aHR] of 1.73 [95% confidence interval, 1.05 to 2.85]).N-acetyl-β-D-glucosaminidase/Crwas associatedwithHFin continuous analyses (aHRper log SD higher 1.18 [95% confidence interval, 1.01 to 1.38]). Only KIM-1/Cr was independently associated with atheroscleroticCVDevents (aHRper logSDhigher 1.21 [95%confidence interval, 1.02 to 1.41]), whereas bothKIM-1/Cr (quintile 5 versus quintile 1 aHR of 1.56 [95% confidence interval, 1.06 to 2.31]) and neutrophil gelatinaseassociated lipocalin/Cr (quintile 5 versus quintile 1 aHR of 1.82 [95% confidence interval, 1.19 to 2.8]) were associated with all-cause death. Conclusions Selected urine kidney injury biomarkerswere independently associatedwith higher risk of HF, CVD events, and death in CRIC. Among the biomarkers examined, only KIM-1/Crwas associatedwith each outcome. Further work is needed to determine the utility of these biomarkers to improve risk prediction for these adverse outcomes.
AB - Background and objectives CKD is an important risk factor for cardiovascular disease (CVD) and death. We investigatedwhether select urine kidney injury biomarkerswere associatedwith higher risk of heart failure (HF), CVD, and death in persons with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Design, setting, participants, & measurements Urine kidney injury molecule-1 (KIM-1), neutrophil gelatinaseassociated lipocalin, liver fatty acid-binding protein, and N-acetyl-β-D-glucosaminidase were measured in urine of a subset of CRIC participants (n=2466).We used Cox proportional hazards regression to examine associations between these biomarkers indexed to urinary creatinine (Cr) and (1) HF, (2) a composite of atherosclerotic CVD events (myocardial infarction, ischemic stroke, or peripheral artery disease), and (3) all-cause death. Results At baseline, mean age of study participants was 59.5±10.8 years, 46% were women, and 34% had a selfreported history of any CVD. Median follow-up was 6.5 (interquartile range, 5.6-6.8) years. A total of 333 HF events, 282 atherosclerotic CVD events, and 440 deaths were observed during a median follow-up of 6.5 (interquartile range, 5.6-6.8) years. Those in the highest two quintiles of KIM-1/Cr levels had a higher risk of HF relative to the lowest quintile (quintile 5 versus quintile 1 adjusted hazard ratio [aHR] of 1.73 [95% confidence interval, 1.05 to 2.85]).N-acetyl-β-D-glucosaminidase/Crwas associatedwithHFin continuous analyses (aHRper log SD higher 1.18 [95% confidence interval, 1.01 to 1.38]). Only KIM-1/Cr was independently associated with atheroscleroticCVDevents (aHRper logSDhigher 1.21 [95%confidence interval, 1.02 to 1.41]), whereas bothKIM-1/Cr (quintile 5 versus quintile 1 aHR of 1.56 [95% confidence interval, 1.06 to 2.31]) and neutrophil gelatinaseassociated lipocalin/Cr (quintile 5 versus quintile 1 aHR of 1.82 [95% confidence interval, 1.19 to 2.8]) were associated with all-cause death. Conclusions Selected urine kidney injury biomarkerswere independently associatedwith higher risk of HF, CVD events, and death in CRIC. Among the biomarkers examined, only KIM-1/Crwas associatedwith each outcome. Further work is needed to determine the utility of these biomarkers to improve risk prediction for these adverse outcomes.
KW - Acetylglucosaminidase
KW - Aged
KW - Atherosclerosis
KW - Biomarkers
KW - Cardiovascular disease
KW - Chronic kidney disease
KW - Creatinine
KW - FABP1 protein, human
KW - Fatty Acid-Binding Proteins
KW - Female
KW - Follow-Up Studies
KW - Heart failure
KW - Humans
KW - Lipocalin-2
KW - Middle Aged
KW - Mortality risk
KW - Myocardial Infarction
KW - Peripheral Arterial Disease
KW - Renal Insufficiency, Chronic
KW - Risk factors
KW - Self Report
KW - Stroke
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UR - http://www.scopus.com/inward/citedby.url?scp=85021702854&partnerID=8YFLogxK
U2 - 10.2215/CJN.08560816
DO - 10.2215/CJN.08560816
M3 - Article
C2 - 28254771
AN - SCOPUS:85021702854
SN - 1555-9041
VL - 12
SP - 761
EP - 771
JO - Clinical journal of the American Society of Nephrology : CJASN
JF - Clinical journal of the American Society of Nephrology : CJASN
IS - 5
ER -