title: Trefoil factor 3 predicts incident chronic kidney disease: a case-control study nested within the Atherosclerosis Risk in Communities (ARIC) study.
abstract: BACKGROUND
  Early detection of individuals at high risk for chronic kidney disease (CKD) may aid prevention. Urinary levels of trefoil factor 3 (TFF3) are associated with acute kidney injury in animal models, but the association of TFF3 levels with incident CKD in humans is unknown.
  
  
  METHODS
  We conducted a case-control study nested within the Atherosclerosis Risk in Communities (ARIC) Study and the ARIC Carotid MRI Study to determine whether urinary TFF3 levels predict incident CKD over 8.6 years of follow-up. A total of 143 participants with incident CKD (eGFR decreasing by ≥25% to <60 ml/min/1.73 m(2)) were matched on age, sex and race to 143 non-cases.
  
  
  RESULTS
  Higher TFF3 levels at baseline were strongly associated with Black race, diabetes (both p = 0.002), and antihypertensive medication use (p = 0.02). Compared to participants with TFF3 levels in the lowest quartile, the odds ratio (OR) of incident CKD was 1.84 (95% confidence interval (CI): 0.80, 4.22) for individuals with TFF3 levels in the second quartile, 2.43 (95% CI: 1.06, 5.53) for the third quartile, and 2.77 (95% CI: 1.22, 6.28) for the fourth quartile (p trend = 0.02). Adjustment for covariates, including urinary albumin: creatinine ratio, did not markedly change the associations. Twofold higher TFF3 levels were strongly associated with incident CKD after adjustment for CKD risk factors (adjusted OR = 1.35; 95% CI: 1.11, 1.64).
  
  
  CONCLUSIONS
  Higher urinary TFF3 levels may indicate ongoing repair of damage in the kidney. Additional studies are needed to confirm whether TFF3 can be useful as a marker of increased risk for CKD.
authors.affiliation: Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, 2024 East Monument Street, Baltimore, MD 21287, USA. bastor@jhsph.edu
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.forename: Anna
authors.initials: A
authors.lastname: Köttgen
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Nrupen
authors.initials: N
authors.lastname: Bhavsar
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
mesh_terms: D000419:Albuminuria / Q000473:pathology; D050197:Atherosclerosis / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010455:Peptides / Q000378:metabolism* / Q000502:physiology* / Q000652:urine; D011336:Probability; D012306:Risk; D000071165:Trefoil Factor-3
chemical_list: D015415:Biomarkers; D010455:Peptides; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3