Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study.
OBJECTIVE
Liver fatty acid binding protein (L-FABP), kidney injury molecule 1 (KIM-1), N-acetyl-β-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.


METHODS
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.
Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
Meredith C
MC
Foster
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Josef
J
Coresh
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Joseph V
JV
Bonventre
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Venkata S
VS
Sabbisetti
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Sushrut S
SS
Waikar
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Theodore E
TE
Mifflin
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Robert G
RG
Nelson
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Morgan
M
Grams
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Harold I
HI
Feldman
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Ramachandran S
RS
Vasan
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Paul L
PL
Kimmel
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Chi-Yuan
CY
Hsu
Due to the number of contributing authors, the affiliations are provided in the Supplemental Material. kathleen.liu@ucsf.edu.
Kathleen D
KD
Liu
D050197:Atherosclerosis; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000453:epidemiology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D018570:Risk Assessment
D015415:Biomarkers
acetylglucosaminidase; albuminuria; chronic; chronic kidney disease; diabetes mellitus; end-stage renal disease; fatty acid-binding proteins; kidney failure; lipocalins; renal insufficiency