Abstract
Abstract Background and Aims Diarrhea is a common gastrointestinal (GI) complaint among kidney transplant recipients (KTR). Exhaled hydrogen (H2) is a surrogate marker of small intestinal bacterial overgrowth, which has been proposed to drive GI symptoms such as diarrhea. In a large cohort of KTR, we assessed the amount of exhaled H2 to evaluate its association with diarrhea and potential clinical and dietary determinants. Method Clinical, laboratory and dietary data from the TransplantLines Biobank and Cohort Study (NCT03272841), comprising 424 KTR were analyzed. Exhaled H2 concentration was measured using a model DP Quintron Gas Chromatograph. Diarrhea was classified according to the Bristol Stool Form Scale (BSFS) and stool water content was measured using a freeze-drying method. Dietary intake was assessed using a validated self-administered food frequency questionnaire (FFQ). Possible determinants of exhaled H2, such as sex, age, eGFR, mycophenolate mofetil and tacrolimus use, and several other clinical, biochemical and nutritional factors, were studied using univariable linear regression. All variables with a p<0.05 were included in a multivariable linear regression model run backward to identify the determinants of exhaled H2 production. Results KTR (55.4±13.2 years, 60.8% male, mean eGFR 49.8±19.1 mL/min/1,73 m2) were divided into three groups according to median exhaled H2 concentration (G1, 1.0-6.9 ppm, n=151; G2, 7.0-19.9 ppm, n=139; G3, ≥20.0 ppm, n=134). Hence, signs of small intestinal bacterial overgrowth (exhaled H2 ≥20 ppm) were identified in 31.6% of KTR. Seventy-six patients (33.0%) had diarrhea according to BSFS. Exhaled H2 correlated with stool water content (r=0.24, p=0.04) and increased risk of diarrhea (OR = 6.03, 95% CI 1.6-22.1, p<0.01). In multivariable linear regression analyses, polysaccharide intake was independently associated with exhaled H2 (std. β=0.24, p=0.01), whereas the other factors were not significant. Conclusion These findings suggest that higher fasting exhaled H2 is associated with increased risk of diarrhea in KTR with polysaccharide intake as an independent determinant of exhaled H2. The present results suggest that diarrhea in KTR may reflect an altered small bowel gut microbial composition, at least partly under dietary influence.
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