title: Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) as predictors of incident CKD stage 3: the Atherosclerosis Risk in Communities (ARIC) Study.
abstract: BACKGROUND
  Identifying individuals at risk of chronic kidney disease (CKD) is critical for timely treatment initiation to slow progression of the disease. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) are known biomarkers of acute kidney injury, but it is unknown whether these markers are associated with incident CKD stage 3 in the general population.
  
  
  METHODS
  Matched case-control study.
  
  
  METHODS
  African American and white participants from the Atherosclerosis Risk in Communities (ARIC) Study who at baseline had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and urinary albumin-creatinine ratio ≤30 mg/g. 143 controls were matched for age, sex, and race to 143 cases of incident CKD stage 3 after 8.6 years of follow-up.
  
  
  METHODS
  Quartile of NGAL and KIM-1.
  
  
  METHODS
  Incident CKD stage 3 (eGFR <60 mL/min/1.73 m(2) at follow-up and a decrease in eGFR from baseline to follow-up ≥25%).
  
  
  RESULTS
  Both NGAL (P = 0.05) and KIM-1 levels (P < 0.001) were correlated positively with baseline urinary albumin-creatinine ratio; neither was associated with baseline eGFR. Participants with NGAL concentrations in the fourth quartile had more than 2-fold higher odds (adjusted OR, 2.11; 95% CI, 0.96-4.64) of incident CKD stage 3 compared with participants in the first quartile after multivariable adjustment (P-trend = 0.03). Adjustment for urinary creatinine and albumin levels resulted in a nonsignificant association (highest quartile adjusted OR, 1.52; 95% CI, 0.64-3.58; P = 0.2). No significant association between KIM-1 level and incident CKD was observed in crude or adjusted models.
  
  
  CONCLUSIONS
  The relatively small sample size of the study limits precision and power to detect weak associations.
  
  
  CONCLUSIONS
  Higher NGAL, but not KIM-1, levels were associated with incident CKD stage 3. Adjustment for urinary creatinine and albumin concentration attenuated this association. Additional studies are needed to confirm these findings and assess the utility of urinary NGAL as a marker of CKD risk.
authors.affiliation: Welch Center for Prevention, Epidemiology and Clinical Research, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Nrupen A
authors.initials: NA
authors.lastname: Bhavsar
authors.forename: Anna
authors.initials: A
authors.lastname: Köttgen
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine*; D000419:Albuminuria / Q000453:epidemiology; D050197:Atherosclerosis / Q000208:ethnology; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood / Q000652:urine; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007676:Kidney Failure, Chronic; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000652:urine*; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus / Q000097:blood*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D003404:Creatinine