title: Intestinal infection at onset of mycophenolic acid-associated chronic diarrhea in kidney transplant recipients.
abstract: BACKGROUND
  Chronic diarrhea after kidney transplantation is often attributed to mycophenolic acid (MPA) toxicity. We hypothesize that intestinal infections contribute to the pathogenesis of chronic MPA-associated diarrhea.
  
  
  METHODS
  In this retrospective study, all patients (n = 726) receiving a kidney transplant between 2000 and 2010 at the University Hospital Zurich were followed until July 2014 for occurrence of chronic diarrhea (≥4 weeks). Infectious triggers at diarrhea onset were assessed by reviewing medical history, stool microbiology, and histology of colon biopsies.
  
  
  RESULTS
  In 46 patients (6.3% of the cohort), a total of 51 episodes of chronic diarrhea during MPA treatment were documented. The diarrhea episodes were often severe, as confirmed by significant weight loss. The cumulative incidence of chronic diarrhea was uniformly distributed throughout the post-transplant period, with 2.0%, 5.1%, and 9.6% at 1, 5, and 10 years, respectively. Evidence was found for intestinal infection at diarrhea onset in 38 episodes (74.5%). Occurrence of diarrhea onset showed a seasonal distribution with peaks in April and October/November. Specific antimicrobial treatment alone was associated with a 19% resolution rate only, whereas combination with dose reduction of MPA or switch from mycophenolate mofetil to enteric-coated mycophenolate sodium resulted in a 22.7% and 76.5% resolution rate, respectively. Change to an MPA-free regimen was associated with a 100% resolution rate.
  
  
  CONCLUSIONS
  These results provide first evidence for a contribution of intestinal infections in chronic post-transplant diarrhea associated with MPA treatment.
authors: Division of Nephrology, University Hospital Zürich, Zürich, Switzerland.
authors: S
authors: http://orcid.org/0000-0002-1050-2800
authors: S
authors: von Moos
authors: Division of Nephrology, University Hospital Zürich, Zürich, Switzerland.
authors: P E
authors: PE
authors: Cippà
authors: Division of Nephrology, University Hospital Zürich, Zürich, Switzerland.
authors: R P
authors: RP
authors: Wüthrich
authors: Division of Nephrology, University Hospital Zürich, Zürich, Switzerland. thomas.mueller@usz.ch.
authors: T F
authors: TF
authors: Mueller
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002908:Chronic Disease; D003092:Colitis / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D003106:Colon / Q000382:microbiology* / Q000473:pathology; D003967:Diarrhea / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology*; D005243:Feces / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D013557:Switzerland / Q000453:epidemiology; D066027:Transplant Recipients; D014184:Transplantation, Homologous / Q000009:adverse effects; D015431:Weight Loss
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
keywords: chronic post-transplant diarrhea; infectious trigger; intestinal infection; mycophenolic acid-related diarrhea