title: Association of urinary KIM-1, L-FABP, NAG and NGAL with incident end-stage renal disease and mortality in American Indians with type 2 diabetes mellitus.
abstract: OBJECTIVE
  Kidney injury molecule 1 (KIM-1), liver fatty acid-binding protein (L-FABP), N-acetyl-β-D-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) are urinary biomarkers of renal tubular injury. We examined their association with incident end-stage renal disease (ESRD) and all-cause mortality in American Indians with type 2 diabetes.
  
  
  METHODS
  Biomarker concentrations were measured in baseline urine samples in 260 Pima Indians who were followed for a median of 14 years. HRs were reported per SD of creatinine (Cr)-normalised log-transformed KIM-1, NAG and NGAL, and for three categories of L-FABP.
  
  
  RESULTS
  During follow-up, 74 participants developed ESRD and 101 died. Median concentrations of KIM-1/Cr, NAG/Cr and NGAL/Cr and the proportion of detectable L-FABP were highest in those with macroalbuminuria (p < 0.001 for KIM-1/Cr, NAG/Cr and L-FABP; p = 0.006 for NGAL/Cr). After multivariable adjustment, NGAL/Cr was positively associated with ESRD (HR 1.59, 95% CI 1.20, 2.11) and mortality (HR 1.39, 95% CI 1.06, 1.82); L-FABP/Cr was inversely associated with ESRD (HR [for highest vs lowest tertile] 0.40, 95% CI 0.19, 0.83). Addition of NGAL/Cr to models that included albuminuria and glomerular filtration rate increased the c-statistic for predicting ESRD from 0.828 to 0.833 (p = 0.001) and for death from 0.710 to 0.722 (p = 0.018). Addition of L-FABP/Cr increased the c-statistic for ESRD from 0.828 to 0.832 (p = 0.042).
  
  
  CONCLUSIONS
  In Pima Indians with type 2 diabetes, urinary concentrations of NGAL and L-FABP are associated with important health outcomes, but they are unlikely to add to risk prediction with standard markers in a clinically meaningful way given the small increase in the c-statistic.
authors.affiliation: Diabetes Epidemiology and Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 1550 East Indian School Road, Phoenix, AZ, 85014-4972, USA.
authors.forename: Gudeta D
authors.initials: GD
authors.lastname: Fufaa
authors.forename: E Jennifer
authors.initials: EJ
authors.lastname: Weil
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nelson
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hanson
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.forename: Venkata
authors.initials: V
authors.lastname: Sabbisetti
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Mifflin
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.forename: Dawei
authors.initials: D
authors.lastname: Xie
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kimmel
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine; D000293:Adolescent; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000208:ethnology / Q000401:mortality* / Q000652:urine*; D003928:Diabetic Nephropathies / Q000208:ethnology / Q000401:mortality* / Q000652:urine*; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D015994:Incidence; D007198:Indians, North American / Q000706:statistics & numerical data; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000401:mortality* / Q000652:urine*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000652:urine; D011991:Receptors, Virus; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; C117339:NBAS protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus