title: Associations of urinary levels of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) with kidney function decline in the Multi-Ethnic Study of Atherosclerosis (MESA).
abstract: BACKGROUND
  Whether elevations in levels of urinary biomarkers of tubular injury (urine neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule 1 [KIM-1]) are associated with future risk of kidney disease has not been investigated.
  
  
  METHODS
  1:1 nested case-control study.
  
  
  METHODS
  686 participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
  
  
  METHODS
  NGAL and KIM-1 were measured at baseline, expressed as log-transformed continuous variables, and categorized into deciles.
  
  
  RESULTS
  Kidney function was estimated by cystatin C level using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Incident CKD stage 3 was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and an eGFR decrease >1 mL/min/1.73 m(2) per year, and rapid kidney function decrease was defined as decrease ≥3 mL/min/1.73 m(2) per year.
  
  
  METHODS
  Cases were defined as persons with eGFR >60 mL/min/1.73 m(2) who subsequently developed incident CKD stage 3 and/or had rapid kidney function decrease by the MESA year-5 visit. Controls were matched for age, sex, race, diabetes, and baseline eGFR. We adjusted for age, hypertension, and presence of albuminuria (albumin-creatinine ratio ≥30 mg/g).
  
  
  RESULTS
  Of 343 cases, 145 had incident CKD stage 3, 141 had rapid kidney function decrease, and 57 had both. Mean eGFR for controls was 81 ± 10 mL/min/1.73 m(2) at baseline and 80 ± 10 mL/min/1.73 m(2) at follow-up compared with 82 ± 13 and 58 ± 10 mL/min/1.73 m(2) for cases. Each doubling of KIM-1 level (in picograms per milliliter) was associated with an OR of 1.15 (95% CI, 1.02-1.29) for incident CKD stage 3 and/or rapid kidney function decrease. Compared with the lowest 90%, the highest decile of KIM-1 level was associated with an OR of 2.02 (95% CI, 1.15-3.56) for the outcome; these associations were independent of albuminuria. NGAL levels (in nanograms per milliliter) were not associated with incident CKD stage 3 and/or rapid kidney function decrease (OR, 1.04; 95% CI, 0.99-1.10). Results were similar when KIM-1 and NGAL levels were standardized for urine creatinine.
  
  
  CONCLUSIONS
  The case-control design limits the ability to account for persons who died or were not available for follow-up.
  
  
  CONCLUSIONS
  Urinary KIM-1 level is associated with future risk of kidney disease independent of albuminuria. Urinary biomarkers of tubular injury are a promising tool for identifying persons at risk of CKD.
authors: San Francisco VA Medical Center, San Francisco, CA 94121, USA. carmenalicia.peralta@ucsf.edu
authors: Carmen A
authors: CA
authors: Peralta
authors: Ronit
authors: R
authors: Katz
authors: Joseph V
authors: JV
authors: Bonventre
authors: Venkata
authors: V
authors: Sabbisetti
authors: David
authors: D
authors: Siscovick
authors: Mark
authors: M
authors: Sarnak
authors: Michael G
authors: MG
authors: Shlipak
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine*; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000208:ethnology / Q000652:urine; D050197:Atherosclerosis / Q000208:ethnology* / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D005006:Ethnicity / Q000208:ethnology; D005260:Female; D005500:Follow-Up Studies; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007674:Kidney Diseases / Q000208:ethnology* / Q000652:urine*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus
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