OXALATE-DEGRADING ACTIVITY IN FECAL MICROBIOTA IS ASSOCIATED WITH OBESITY AND CARDIOVASCULAR EVENTS IN END-STAGE KIDNEY DISEASE PATIENTS

Abstract

Objective: In contrast to the general population, the obesity paradox observed in end-stage kidney disease (ESKD) patients is associated with a better CVD prognosis. Considering the similar signature of the gut microbiota in oxalate metabolism, obesity, and CVD, we hypothesized that altered oxalate-degrading activity (ODA) in the fecal microbiota, rather than obesity per se, might influence the development of CVD in ESKD patients. Design and method: A total of 32 ESKD patients aged 52.5 (40-62) years were enrolled in this retrospective observational cohort pilot study. CVD events were defined as any new-onset disease of the heart and associated blood vessels during the 3-year follow-up period after completion of evaluation. The fecal total ODA, defined as the total ability of the different strains of oxalate-degrading bacteria to metabolize oxalate, was determined by redoximetric titration with KMnO4; results were expressed as % oxalate degradation per 0.01 g of feces. Data analysis and all graphs were generated using MedCalc software. Results: Total fecal ODA ranged from -16 to 24%/0.01 g feces and was inversely correlated with BMI (Fig. 1). During the 3-year follow-up period, 5/7 (71.4%) obese patients, 2/11 (18.2%) overweight patients, and 2/14 (14.3%) normal-weight patients experienced CVD (⇙2 = 8.4, p = 0.01). The ROC analysis showed that a negative total fecal ODA (<-1%/0.01 g feces) was the most appropriate cut-off point for predicting CVD events in ESKD patients, with a sensitivity of 77.8% and a specificity of 74% (Fig. 2). In univariate Cox regression analysis, both obesity (HR 8.2, 95% CI 1.2; 18.1) and negative fecal total ODA (HR 9.4, 95% CI 2.3; 19.4) were associated with CVD events. In the multivariate model of Cox regression analysis adjusted for age, dialysis vintage, diabetes, and dyslipidemia, negative total fecal ODA, but not obesity, was associated with CVD events in our cohort (Fig. 3). Conclusions: Our findings provide preliminary evidence that a decrease in fecal total ODA is associated with obesity and the development of CVD in ESKD patients. Further studies are needed to determine altered fecal total ODA as a risk factor for the development of CVD in ESKD patients.