Abstract: TH-PO518

Randomized, Placebo-Controlled Trial of Rifaximin Therapy for Lowering Gut-Derived Cardiovascular Toxins in CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 305 CKD: Clinical Trials and Tubulointerstitial Disorders


  • 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

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.


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.


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.


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.


  • Other NIH Support