Assessing intestinal permeability in Crohn’s disease patients using orally administered (52)Cr-EDTA

BACKGROUND: Intestinal permeability can be assessed by monitoring renal excretion of orally administered radioactively (51)Cr-labeled ethylenediaminetetraacetic acid ((51)Cr-EDTA). Although considered safe, patient participation in using radio-labeled tracers is low. Here, we used orally administered (52)Cr-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 (52)Cr-EDTA (20 mmol/L) solution whereafter 24-h urine was collected. Urinary (52)Cr-EDTA concentrations were quantified using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Fecal Enterobacteriaceae and Faecalibacterium prausnitzii were quantified using FISH. Correlations between urinary (52)Cr-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 (52)Cr-EDTA/creatinine ratio (772 vs. 636 μmol/mol, P = 0.132). Patients with primarily colonic disease showed the highest (52)Cr-EDTA excretion. Importantly, a positive correlation was observed for the urinary (52)Cr-EDTA/creatinine ratio and fecal calprotectin levels (ρ = 0.325, P < 0.05). Finally, urinary (52)Cr-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 (52)Cr-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.