title: Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial.
abstract: Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome.
  
  
  
  We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1.73 m(2)), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression.
  
  
  
  Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio.
  
  
  
  Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function.
authors.affiliation: Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Girish N
authors.initials: GN
authors.lastname: Nadkarni
authors.affiliation: Department of Medicine, Division of Nephrology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Veena
authors.initials: V
authors.lastname: Rao
authors.affiliation: Department of Medicine, Division of Clinical and Molecular Endocrinology, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Faramarz
authors.initials: F
authors.lastname: Ismail-Beigi
authors.affiliation: Department of Medicine, Division of Endocrinology, Tulane University, New Orleans, Louisiana.
authors.forename: Vivian A
authors.initials: VA
authors.lastname: Fonseca
authors.affiliation: Department of Medicine, Division of Nephrology, University of Arkansas Medical Sciences, Little Rock, Arkansas; and.
authors.forename: Sudhir V
authors.initials: SV
authors.lastname: Shah
authors.affiliation: Department of Medicine, Division of Clinical and Molecular Endocrinology, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simonson
authors.affiliation: Department of Medicine, Division of Nephrology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Cantley
authors.affiliation: Department of Pediatrics, Division of Nephrology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.affiliation: Department of Medicine, Division of Nephrology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
authors.affiliation: Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Coca
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000652:urine*; D000071451:Chitinase-3-Like Protein 1 / Q000652:urine*; D003404:Creatinine / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology / Q000652:urine*; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000652:urine*; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000652:urine; D020382:Interleukin-18 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; C084533:CHI3L1 protein, human; D018932:Chemokine CCL2; D000071451:Chitinase-3-Like Protein 1; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C000589760:IL18 protein, human; D020382:Interleukin-18; D003404:Creatinine
keywords: Biomarkers; CCL2 protein, human; CHI3L1 protein, human; Diabetes Mellitus, Type 2; Follow-Up Studies; Inflammation; albuminuria; chronic kidney disease; renal fibrosis; renal injury