Exhaled Hydrogen as a Marker of Intestinal Fermentation Is Associated with Diarrhea in Kidney Transplant Recipients

Background: Diarrhea is common among kidney transplant recipients (KTR). Exhaled hydrogen (H(2)) is a surrogate marker of small bowel dysbiosis, which may drive diarrhea. We studied the relationship between exhaled H(2) and diarrhea in KTR, and explored potential clinical and dietary determinants. Methods: Clinical, laboratory, and dietary data were analyzed from 424 KTR participating in the TransplantLines Biobank and Cohort Study (NCT03272841). Fasting exhaled H(2) concentration was measured using a model DP Quintron Gas Chromatograph. Diarrhea was defined as fast transit time (types 6 and 7 according to the Bristol Stool Form Scale, BSFS) of 3 or more episodes per day. We studied the association between exhaled H(2) and diarrhea with multivariable logistic regression analysis, and explored potential determinants using linear regression. Results: KTR (55.4 ± 13.2 years, 60.8% male, mean eGFR 49.8 ± 19.1 mL/min/1.73 m(2)) had a median exhaled H(2) of 11 (5.0–25.0) ppm. Signs of small intestinal bacterial overgrowth (exhaled H(2) ≥ 20 ppm) were present in 31.6% of the KTR, and 33.0% had diarrhea. Exhaled H(2) was associated with an increased risk of diarrhea (odds ratio 1.51, 95% confidence interval 1.07–2.14 per log(2) ppm, p = 0.02). Polysaccharide intake was independently associated with higher H(2) (std. β 0.24, p = 0.01), and a trend for an association with proton-pump inhibitor use was observed (std. β 0.16 p = 0.05). Conclusion: Higher exhaled H(2) is associated with an increased risk of diarrhea in KTR. Our findings set the stage for further studies investigating the relationship between dietary factors, small bowel dysbiosis, and diarrhea after kidney transplantation.