Abstract: TH-PO473

Gut Microbiome Derived Short Chain Fatty Acids Alter with Advancing CKD and Improve Prediction of Associated Cardiovascular Disease

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 303 CKD: Epidemiology, Outcomes - Cardiovascular

Authors

  • Jadoon, Adil, University of Michigan, Ann Arbor, Michigan, United States
  • Mathew, Anna Vachaparampil, University of Michigan, Ann Arbor, Michigan, United States
  • Byun, Jaeman, University of Michigan, Ann Arbor, Michigan, United States
  • Afshinnia, Farsad, University of Michigan, Ann Arbor, Michigan, United States
  • Pennathur, Subramaniam, University of Michigan, Ann Arbor, Michigan, United States
Background

Short chain free fatty acids (SCFA) are products of dietary complex carbohydrate fermentation by the intestinal microbiota and exert multiple effects on mammalian energy metabolism. However, reports of alterations in SCFAs by CKD and association with CVD are lacking. In this study, utilizing targeted metabolomics by liquid-chromatography mass-spectrometry (LC/MS), we quantified SCFAs at different stages of CKD and analyzed their association with CVD.

Methods

This is a cross sectional observational study of the population in Clinical Phenotyping Resource and Biobank Core. Inclusion criteria are patients with CKD, aged older than 18. Clinical and demographic data at the time of enrolment were gathered. Secondary outcomes were history of CAD, CHF and peripheral artery disease (PAD). SCFAs were measured by LC/MS using the plasma at enrolment. We used analysis of variance to compare means by CKD stages, and applied Receiver Operating Characteristics Curve to compare c-statistic of different models.

Results

Overall we enrolled 214 patients, including 36, 99, 61, and 18 patients from stages 2 to 5 of CKD. Mean age was 60 years (SD=16), and 51.4% were males (n=110). We found a significant graded decrease in level of acetate from 14.3±2.8 ug/L in stage 2 to 12.2±1.9 ug/L in stage 5 (p=0.011), but a significant increase in mean level of butyrate, valerate, and caproate from stage 2 to stage 5 (p≤0.018). Specifically, level of valerate increased from 1.8±0.1 ug/L in CKD stage 2 to 1.9±0.3 ug/L in stage 5 (p=0.006), and caproate increased from 1.6±0.1 ug/L to 2.0±1.4 ug/L from CKD stage 2 to 5. Mean±SD of valerate in patients with and without CAD was 1.79±0.08 ug/L and 1.62±0.09 ug/L, respectively (P<0.0001). Similarly, this value was 1.80±0.08 ug/L and 1.84±0.09ug/L in patients with and without CHF, respectively (p=0.037). Compared to a model consisting of age, diabetes, and stages of CKD to predict CAD, addition of valerate significantly improved c-statistic from 0.74 to 0.78 (p=0.029).

Conclusion

This study provides evidence for alterations in gut-microbiome derived SCFAs with advancing CKD and links SCFAs to CVD, suggesting possible contribution of gut microbiome to CKD and its complications.