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Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study.

TitleUrinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study.
Publication TypeJournal Article
Year of Publication2015
AuthorsFoster MC, Coresh JJ, Bonventre JV, Sabbisetti VS, Waikar SS, Mifflin TE, Nelson RG, Grams M, Feldman HI, Vasan RS, Kimmel PL, Hsu C-Y
Secondary AuthorsLiu KD
Corporate AuthorsCKD Biomarkers Consortium
JournalClin J Am Soc Nephrol
Volume10
Issue11
Pagination1956-63
Date Published2015 Nov 06
ISSN1555-905X
KeywordsAtherosclerosis, Biomarkers, Case-Control Studies, Female, Humans, Kidney Failure, Chronic, Male, Middle Aged, Prospective Studies, Risk, Risk Assessment
Abstract

BACKGROUND AND OBJECTIVES: Liver fatty acid binding protein (L-FABP), kidney injury molecule 1 (KIM-1), N-acetyl-╬▓-d-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) are urinary markers of tubular injury that may also be markers of chronic kidney damage. We evaluated the association of these markers with incident ESRD in a community-based sample from the Atherosclerosis Risk in Communities Study.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a matched case-control study of 135 patients with ESRD and 186 controls who were matched on sex, race, kidney function, and diabetes status at baseline (Atherosclerosis Risk in Communities Study visit 4, 1996-1998). Urinary KIM-1 indexed to creatinine (Cr), NAG/Cr, NGAL/Cr, and L-FABP/Cr were measured in stored spot urine samples from the baseline examination. Associations of KIM-1/Cr, NAG/Cr, and NGAL/Cr with patients with incident ESRD through 2008 were modeled continuously and categorically (quartiles) using conditional logistic regression. L-FABP/Cr was modeled only categorically because of a large number of measurements below the lower limit of detection for the assay (2.4 ng/ml).

RESULTS: No significant associations were observed for NAG/Cr, NGAL/Cr, or L-FABP/Cr with ESRD. Those in the highest category for KIM-1/Cr had a higher risk of ESRD compared with those with undetectable biomarker levels (reference group) in unadjusted models (odds ratio, 2.24; 95% confidence interval, 1.97 to 4.69; P=0.03) or adjustment for age (odds ratio, 2.23; 95% confidence interval, 1.06 to 4.67; P=0.03). This association was attenuated with additional adjustment for baseline kidney function (odds ratio, 2.02; 95% confidence interval, 0.95 to 4.31; P=0.07 after additional adjustment for eGFR and natural log of the urinary albumin-to-creatinine ratio). No association between KIM-1/Cr and ESRD was found when KIM-1/Cr was analyzed as a continuous variable.

CONCLUSIONS: Elevated urinary KIM-1/Cr may be associated with a higher risk of incident ESRD, but it does not add to risk prediction after accounting for traditional markers of kidney function in this population.

DOI10.2215/CJN.02590315
Alternate JournalClin J Am Soc Nephrol
PubMed ID26350438
PubMed Central IDPMC4633784
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
U01DK085660 / DK / NIDDK NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
U01 DK085660 / DK / NIDDK NIH HHS / United States
U01DK085689 / DK / NIDDK NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
U01DK085688 / DK / NIDDK NIH HHS / United States
U01DK85649 / DK / NIDDK NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
U01 DK085673 / DK / NIDDK NIH HHS / United States
U01DK085673 / DK / NIDDK NIH HHS / United States
R37 DK039773 / DK / NIDDK NIH HHS / United States
U01 DK085651 / DK / NIDDK NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
/ / Intramural NIH HHS / United States
R01 DK072381 / DK / NIDDK NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
U01DK085651 / DK / NIDDK NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
U01 DK085649 / DK / NIDDK NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
U01 DK085689 / DK / NIDDK NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
U01 DK085688 / DK / NIDDK NIH HHS / United States