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Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: The CRIC Study.
Clin J Am Soc Nephrol. 2017 May 08; 12(5):761-771.CJ

Abstract

BACKGROUND AND OBJECTIVES

CKD is an important risk factor for cardiovascular disease (CVD) and death. We investigated whether select urine kidney injury biomarkers were associated with 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 gelatinase-associated 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 self-reported 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/Cr was associated with HF in continuous analyses (aHR per log SD higher 1.18 [95% confidence interval, 1.01 to 1.38]). Only KIM-1/Cr was independently associated with atherosclerotic CVD events (aHR per log SD higher 1.21 [95% confidence interval, 1.02 to 1.41]), whereas both KIM-1/Cr (quintile 5 versus quintile 1 aHR of 1.56 [95% confidence interval, 1.06 to 2.31]) and neutrophil gelatinase-associated 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 biomarkers were independently associated with higher risk of HF, CVD events, and death in CRIC. Among the biomarkers examined, only KIM-1/Cr was associated with each outcome. Further work is needed to determine the utility of these biomarkers to improve risk prediction for these adverse outcomes.

Authors+Show Affiliations

Division of Nephrology, University of California, San Francisco, San Francisco, California; Meyeon.Park@ucsf.edu.Division of Nephrology, University of California, San Francisco, San Francisco, California.Division of Research, Kaiser Permanente Northern California, Oakland, California.Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania.Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania.Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania.Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania.Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland.National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.Division of Nephrology and Hypertension, Case Western Reserve University, Cleveland, Ohio; and.Division of Nephrology and Hypertension, Case Western Reserve University, Cleveland, Ohio; and.Section of Preventive Medicine and Epidemiology, Boston University, Boston, Massachusetts.Division of Nephrology, University of California, San Francisco, San Francisco, California.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

28254771

Citation

Park, Meyeon, et al. "Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: the CRIC Study." Clinical Journal of the American Society of Nephrology : CJASN, vol. 12, no. 5, 2017, pp. 761-771.
Park M, Hsu CY, Go AS, et al. Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: The CRIC Study. Clin J Am Soc Nephrol. 2017;12(5):761-771.
Park, M., Hsu, C. Y., Go, A. S., Feldman, H. I., Xie, D., Zhang, X., Mifflin, T., Waikar, S. S., Sabbisetti, V. S., Bonventre, J. V., Coresh, J., Nelson, R. G., Kimmel, P. L., Kusek, J. W., Rahman, M., Schelling, J. R., Vasan, R. S., & Liu, K. D. (2017). Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: The CRIC Study. Clinical Journal of the American Society of Nephrology : CJASN, 12(5), 761-771. https://doi.org/10.2215/CJN.08560816
Park M, et al. Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: the CRIC Study. Clin J Am Soc Nephrol. 2017 May 8;12(5):761-771. PubMed PMID: 28254771.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: 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, AU - ,, AU - ,, Y1 - 2017/03/02/ PY - 2016/08/11/received PY - 2017/01/19/accepted PY - 2017/3/4/pubmed PY - 2018/3/6/medline PY - 2017/3/4/entrez KW - Acetylglucosaminidase KW - Aged KW - Atherosclerosis KW - Biomarkers KW - FABP1 protein, human KW - Fatty Acid-Binding Proteins KW - Female KW - Follow-Up Studies KW - Humans KW - Lipocalin-2 KW - Middle Aged KW - Myocardial Infarction KW - Peripheral Arterial Disease KW - Renal Insufficiency, Chronic KW - Self Report KW - Stroke KW - cardiovascular disease KW - chronic kidney disease KW - creatinine KW - heart failure KW - mortality risk KW - risk factors SP - 761 EP - 771 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 12 IS - 5 N2 - BACKGROUND AND OBJECTIVES: CKD is an important risk factor for cardiovascular disease (CVD) and death. We investigated whether select urine kidney injury biomarkers were associated with 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 gelatinase-associated 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 self-reported 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/Cr was associated with HF in continuous analyses (aHR per log SD higher 1.18 [95% confidence interval, 1.01 to 1.38]). Only KIM-1/Cr was independently associated with atherosclerotic CVD events (aHR per log SD higher 1.21 [95% confidence interval, 1.02 to 1.41]), whereas both KIM-1/Cr (quintile 5 versus quintile 1 aHR of 1.56 [95% confidence interval, 1.06 to 2.31]) and neutrophil gelatinase-associated 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 biomarkers were independently associated with higher risk of HF, CVD events, and death in CRIC. Among the biomarkers examined, only KIM-1/Cr was associated with each outcome. Further work is needed to determine the utility of these biomarkers to improve risk prediction for these adverse outcomes. SN - 1555-905X UR - https://www.unboundmedicine.com/medline/citation/28254771/Urine_Kidney_Injury_Biomarkers_and_Risks_of_Cardiovascular_Disease_Events_and_All_Cause_Death:_The_CRIC_Study_ L2 - https://cjasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=28254771 DB - PRIME DP - Unbound Medicine ER -