title: Urinary Vitamin D Binding Protein and KIM-1 Are Potent New Biomarkers of Major Adverse Renal Events in Patients Undergoing Coronary Angiography.
abstract: BACKGROUND
  Vitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. Acute tubular injury is expected to result in urinary VDBP loss. The purpose of our study was to explore the potential role of urinary VDBP as a biomarker of an acute renal damage.
  
  
  METHODS
  We included 314 patients with diabetes mellitus or mild renal impairment undergoing coronary angiography and collected blood and urine before and 24 hours after the CM application. Patients were followed for 90 days for the composite endpoint major adverse renal events (MARE: need for dialysis, doubling of serum creatinine after 90 days, unplanned emergency rehospitalization or death).
  
  
  RESULTS
  Increased urine VDBP concentration 24 hours after contrast media exposure was predictive for dialysis need (no dialysis: 113.06 ± 299.61 ng/ml, n = 303; need for dialysis: 613.07 ± 700.45 ng/ml, n = 11, Mean ± SD, p<0.001), death (no death during follow-up: 121.41 ± 324.45 ng/ml, n = 306; death during follow-up: 522.01 ± 521.86 ng/ml, n = 8; Mean ± SD, p<0.003) and MARE (no MARE: 112.08 ± 302.00 ng/ml, n = 298; MARE: 506.16 ± 624.61 ng/ml, n = 16, Mean ± SD, p<0.001) during the follow-up of 90 days after contrast media exposure. Correction of urine VDBP concentrations for creatinine excretion confirmed its predictive value and was consistent with increased levels of urinary Kidney Injury Molecule-1 (KIM-1) and baseline plasma creatinine in patients with above mentioned complications. The impact of urinary VDBP and KIM-1 on MARE was independent of known CIN risk factors such as anemia, preexisting renal failure, preexisting heart failure, and diabetes.
  
  
  CONCLUSIONS
  Urinary VDBP is a promising novel biomarker of major contrast induced nephropathy-associated events 90 days after contrast media exposure.
authors.affiliation: Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany.|Department of Vascular Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Lyubov
authors.initials: L
authors.lastname: Chaykovska
authors.affiliation: Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Heunisch
authors.affiliation: Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Gina
authors.initials: G
authors.lastname: von Einem
authors.affiliation: Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Markus L
authors.initials: ML
authors.lastname: Alter
authors.affiliation: Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Carl-Friedrich
authors.initials: CF
authors.lastname: Hocher
authors.affiliation: Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Oleg
authors.initials: O
authors.lastname: Tsuprykov
authors.affiliation: Immundiagnostik AG, Bensheim, Germany.|Department of Cardiology and Angiology, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dschietzig
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Kretschmer
authors.affiliation: Institute for Nutritional Science, University of Potsdam, Potsdam, Germany.|IFLb Laboratoriumsmedizin Berlin GmbH, Berlin, Germany.
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000401:mortality / Q000473:pathology / Q000652:urine*; D000368:Aged; D000740:Anemia / Q000401:mortality / Q000473:pathology / Q000652:urine; D015415:Biomarkers; D002112:Calcifediol / Q000652:urine; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D017023:Coronary Angiography / Q000009:adverse effects*; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000401:mortality / Q000473:pathology / Q000652:urine; D005260:Female; D006333:Heart Failure / Q000401:mortality / Q000473:pathology / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011991:Receptors, Virus; D006435:Renal Dialysis; D016019:Survival Analysis; D014809:Vitamin D-Binding Protein / Q000652:urine*
chemical_list: D015415:Biomarkers; D003287:Contrast Media; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D014809:Vitamin D-Binding Protein; D003404:Creatinine; D002112:Calcifediol