Urinary Vitamin D Binding Protein and KIM-1 Are Potent New Biomarkers of Major Adverse Renal Events in Patients Undergoing Coronary Angiography

PLoS One. 2016 Jan 11;11(1):e0145723. doi: 10.1371/journal.pone.0145723. eCollection 2016.

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.

Method: 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.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / mortality
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / urine*
  • Aged
  • Anemia / mortality
  • Anemia / pathology
  • Anemia / urine
  • Biomarkers
  • Calcifediol / urine
  • Contrast Media / administration & dosage
  • Contrast Media / adverse effects*
  • Coronary Angiography / adverse effects*
  • Creatinine / urine
  • Diabetes Mellitus, Type 1 / mortality
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / urine
  • Female
  • Heart Failure / mortality
  • Heart Failure / pathology
  • Heart Failure / urine
  • Hepatitis A Virus Cellular Receptor 1
  • Humans
  • Kidney / metabolism*
  • Kidney / pathology
  • Male
  • Membrane Glycoproteins / urine*
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Receptors, Virus
  • Renal Dialysis
  • Survival Analysis
  • Vitamin D-Binding Protein / urine*

Substances

  • Biomarkers
  • Contrast Media
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Membrane Glycoproteins
  • Receptors, Virus
  • Vitamin D-Binding Protein
  • Creatinine
  • Calcifediol

Grants and funding

Bayer Pharma AG, Wuppertal, Germany provided measurements of KIM-1 and VDBP in urine as well as salary for author [AK], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these author is articulated in the Author Contributions section.