Assessing intestinal permeability in Crohn's disease patients using orally administered 52Cr-EDTA

PLoS One. 2019 Feb 7;14(2):e0211973. doi: 10.1371/journal.pone.0211973. eCollection 2019.

Abstract

Background: Intestinal permeability can be assessed by monitoring renal excretion of orally administered radioactively 51Cr-labeled ethylenediaminetetraacetic acid (51Cr-EDTA). Although considered safe, patient participation in using radio-labeled tracers is low. Here, we used orally administered 52Cr-EDTA as non-radioactive alternative to assess intestinal permeability in CD and analyzed the association with disease activity, disease location and gut microbial dysbiosis.

Materials and methods: 60 CD patients with low (n = 25) and increased (n = 35) fecal calprotectin levels (cut-off: 100 μg/g feces) ingested 20 mL 52Cr-EDTA (20 mmol/L) solution whereafter 24-h urine was collected. Urinary 52Cr-EDTA concentrations were quantified using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Fecal Enterobacteriaceae and Faecalibacterium prausnitzii were quantified using FISH. Correlations between urinary 52Cr-EDTA excretion and other parameters were established using nonparametric Spearman's correlation coefficients (ρ).

Results: CD patients with increased fecal calprotectin levels (> 100 μg/g) demonstrated an elevated urinary 52Cr-EDTA/creatinine ratio (772 vs. 636 μmol/mol, P = 0.132). Patients with primarily colonic disease showed the highest 52Cr-EDTA excretion. Importantly, a positive correlation was observed for the urinary 52Cr-EDTA/creatinine ratio and fecal calprotectin levels (ρ = 0.325, P < 0.05). Finally, urinary 52Cr-EDTA/creatinine ratio negatively correlated with the relative abundance of Faecalibacterium prausnitzii (ρ = -0.221, P = 0.092), while positively correlating with Enterobacteriaceae (ρ = 0.202, P = 0.126).

Conclusions: Orally administered and renal excreted 52Cr-EDTA may be used to assess intestinal permeability in CD and correlates with fecal calprotectin levels and bacterial species relevant to CD. This test may improve non-invasive detection of disease exacerbations and help monitor disease activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Crohn Disease / complications
  • Crohn Disease / metabolism
  • Crohn Disease / urine*
  • Dysbiosis / diagnosis*
  • Dysbiosis / metabolism
  • Edetic Acid / administration & dosage*
  • Edetic Acid / chemistry
  • Edetic Acid / pharmacokinetics
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae / isolation & purification*
  • Faecalibacterium prausnitzii / genetics
  • Faecalibacterium prausnitzii / isolation & purification*
  • Feces / chemistry
  • Female
  • Humans
  • Intestinal Mucosa / chemistry
  • Leukocyte L1 Antigen Complex / metabolism
  • Mass Spectrometry
  • Middle Aged
  • Patient Participation
  • Permeability
  • Urine / chemistry*
  • Young Adult

Substances

  • Leukocyte L1 Antigen Complex
  • Edetic Acid

Grants and funding

The research position of drs. J.Z.H. von Martels is financed by the Top Institute of Food and Nutrition (TIFN) in Wageningen and the Center for Development & Innovation of the University Medical Center Groningen. The research position of Arno R. Bourgonje is supported by a JSM MD-PhD trajectory grant (grant number: 17-57) from the Junior Scientific Masterclass of the University of Groningen, the Netherlands. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.