Urinary biomarkers and risk of ESRD in the atherosclerosis risk in communities study

Meredith C. Foster, Josef Coresh, Joseph V. Bonventre, Venkata S. Sabbisetti, Sushrut S. Waikar, Theodore E. Mifflin, Robert G. Nelson, Morgan Grams, Harold I. Feldman, Ramachandran S. Vasan, Paul L. Kimmel, Chi Yuan Hsu, Kathleen D. Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Background and objectives Liver fatty acid binding protein (L-FABP), kidney injurymolecule 1 (KIM-1),N-acetylb-D-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) are urinary markers of tubular injury thatmay also be markers of chronic kidney damage.We evaluated the association of thesemarkers 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 whowerematched 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, andNGAL/Crwith patientswith incident ESRDthrough 2008 weremodeled 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.

Original languageEnglish (US)
Pages (from-to)1956-1963
Number of pages8
JournalClinical Journal of the American Society of Nephrology
Volume10
Issue number11
DOIs
StatePublished - Nov 6 2015

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

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