CARDIAC AND METABOLIC COMPLICATIONS OF TRANSPLANTATION

W.H. Marks¹, T.Y. Spinelli¹, S.F. Olmstead^2
1Organ Transplantation, Swedish Medical Center, Seattle/WA/UNITED STATES OF AMERICA, ², Prothera, Inc., Reno/UNITED STATES OF AMERICA

Body: Introduction Immunosuppression following organ transplantation is associated with gastrointestinal (GI) complications. Mycophenolate mofetil (MMF) is most associated with GIcomplaints, usually diarrhea, with a prevalence approaching 50%. Immunosuppression-associated diarrhea (IAD) may occur with other agents. IAD can lead to alterations in the immunosuppressant regimenthereby increasing the risk of acute rejection. Immunosuppressants may alter gut microbiota populations thus reducing short-chain fatty acid (SCFA) production. The consumption of probiotics, viablemicrobes that benefit health, may restore GI microbiota balance and augment colonic SCFA concentrations. We hypothesized that probiotics following kidney transplantation could reduce the incidence ofIAD.

Methods Patients undergoing kidney transplantation were recruited at a single site and randomly assigned to probiotics (n=21) or placebo (n=22). The probiotics were a blend ofBifidobacterium lactis, B. bifidum, B. longum, Lactobacillus acidophilus, L. rhamnosus, and L. paracasei. Each probiotic capsule contained a total of 50 billion colonyforming units (CFU). Subjects took 2 capsules twice daily. Subjects were screened and randomized prior to transplantation. Study agents were started before surgery and continued for 4 months.Subjects were followed for 5 months post transplantation. Stool samples were regularly obtained during follow-up. Questionnaires documenting bowel habits were completed daily. Medical records werereviewed. IAD was defined as >2 consecutives days of 2 loose stools daily unrelated to pathogens or medications other than immunosuppressants. Analyses were per-protocol.

Results 43 subjects were recruited into the study from August 2006 to July 2008. 19 of 21 subjects in the probiotic group completed the study while 16 of 22 patients in the placebo groupcompleted. The 2 groups were comparable in all aspects. IAD occurred in 10 of 16 (62.5%) subjects randomized to placebo and in 3 of 19 (15.8%) subjects receiving probiotics. The reduction in IAD inthe probiotic group was highly significant (P=0.006). Subjects receiving probiotics had significantly less severe diarrhea. Probiotics were well tolerated and there were no study-related adverseevents.

Conclusion Probiotics statistically significantly reduced the incidence and severity of serious IAD following kidney transplantation.

Disclosure: All authors have declared no conflicts of interest.