Abstract: TH-PO518
Randomized, Placebo-Controlled Trial of Rifaximin Therapy for Lowering Gut-Derived Cardiovascular Toxins in CKD
Session Information
- CKD: Clinical Trials and Tubulointerstitial Disorders
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Chronic Kidney Disease (Non-Dialysis)
- 305 CKD: Clinical Trials and Tubulointerstitial Disorders
Authors
- Kimber, Cassandra A., University of Kansas, Kansas City, Kansas, United States
- Johnson, Cassandra R., University of Kansas, Kansas City, Kansas, United States
- Prokopienko, Alexander J., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- McGreal, Kerri A., University of Kansas, Kansas City, Kansas, United States
- Nolin, Thomas D., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Stubbs, Jason R., University of Kansas Medical Center, FAIRWAY, Kansas, United States
Background
Accumulating evidence suggests that byproducts of gut bacteria contribute to cardiovascular morbidity in CKD patients. One example is trimethylamine-N-oxide (TMAO), a pro-atherosclerotic compound generated from metabolites produced by intestinal bacteria. Rifaximin is a minimally absorbed, oral antibiotic that targets intestinal pathogens and can chronically suppress circulating levels of gut-derived bacterial toxins that contribute to disease comorbidities in other patient populations.
Methods
We conducted a randomized, double-blinded, placebo-controlled trial to determine the impact of a 10-day course of oral rifaximin 550 mg BID vs. placebo on serum TMAO and fecal bacterial composition in patients with stage III-V CKD (n=38). Fasting serum, urine and stool samples were collected at baseline and immediately post-therapy. Our primary outcomes of interest were change in serum TMAO and relative abundance of fecal bacterial communities. Secondary analyses of interest included change in serum p-cresol, indoxyl sulfate, and pro-inflammatory cytokines.
Results
Rifaximin therapy decreased the relative abundance of bacterial families known to generate TMAO precursors; mean relative abundance of Clostridiaceae decreased from 0.6 to 0.1% (p<0.01) and Peptostreptococcaceae decreased from 2.2 to 1.4% (p=0.17) in the rifaximin group vs. a change from 0.5 to 0.6% (p=0.21) and 1.3 to 1.9% (p=0.57), respectively, in the placebo group. Despite an apparent reduction in these bacterial populations, we observed only a minor, non-significant reduction in serum TMAO with rifaximin; mean TMAO changed from 18.8 ± 18.7 µM at baseline to 14.8 ± 10.2 µM post-therapy (p=0.31) in the rifaximin group vs. a mean TMAO change from 15.6 ± 11.6 at baseline to 16.1 ± 13.4 µM post-therapy (p=0.84) in the placebo group. Analysis of the stated secondary outcomes is currently ongoing.
Conclusion
Short-term rifaximin therapy effectively suppresses bacteria that generate TMAO precursors; however, these changes in gut flora do not translate to significantly lower serum TMAO in CKD patients.
Funding
- Other NIH Support