title: Late, severe, noninfectious diarrhea after renal transplantation: high-risk factors, therapy, and prognosis.
abstract: OBJECTIVE
  Late severe noninfectious diarrhea in renal transplant recipients can lead to malnutrition and even graft loss. The purpose of this study was to evaluate risk factors associated with this condition and summarize therapy for these patients.
  
  
  METHODS
  For more than 36 months we observed a cohort of 541 recipients who underwent kidney transplantation from January 2001 to June 2007. They were provided a calcineurin inhibitor (CNI) combined with mycophenolate mofetil (MMF). The four group includes a continuous cyclosporine (CsA); a preconversion to tacrolimus and a postconversion group as well as a continuous tacrolimus group. The rate of severe late noninfectious diarrhea was compared among the four groups. Risk factors were analyzed between the diarrhea and nondiarrhea cohorts. Clinical characteristics, efficacy, and safety were observed after modifying the immunosuppressive protocol for late severe noninfectious diarrhea recipients.
  
  
  RESULTS
  Twenty-eight recipients presented with late sever noninfectious diarrhea. No patients displayed chronic diarrhea in the CsA (n = 145) or preconversion group (n = 95). The rate of diarrhea was 7.31% in the postconversion and 7.35% in the tacrolimus group. Using multivariate Cox proportional hazards analysis, factors associated with an increased risk of noninfectious diarrhea were cytochrome P450(CYP)3A5 *3/*3 type, chronic renal allograft dysfunction, and patient ingestion of Tripterygium wilfordii Hook F. All diarrheal recipients experienced weight loss, hypoalbuminia, and an increased serum creatinine. All affected patients underwent adjustment of the immunosuppressive regimen to achieve remission. Renal allograft survival in recipients with diarrhea was worse than that in nondiarrheal recipients receiving tacrolimus combined with MMF.
  
  
  CONCLUSIONS
  Tacrolimus with MMF increased the risk of late severe noninfectious diarrhea among renal transplant recipients compared with hosts treats with CsA plus MMF. The CYP3A5 *3/*3 type, chronic renal allograft dysfunction, and T. wilfordii supplementation were high-risk factors for late diarrhea. Prompt adjustment of immunosuppression was an effective, feasible therapy for these patients.
authors: Department of Transplant Center, Third Xiangya Hospital, Changsha, China.
authors: Y J
authors: YJ
authors: Zhao
authors: J Q
authors: JQ
authors: Wen
authors: K
authors: K
authors: Cheng
authors: Y Z
authors: YZ
authors: Ming
authors: X G
authors: XG
authors: She
authors: H
authors: H
authors: Liu
authors: L
authors: L
authors: Liu
authors: Q F
authors: QF
authors: Ye
authors: B N
authors: BN
authors: Ding
mesh_terms: D000293:Adolescent; D000328:Adult; D016009:Chi-Square Distribution; D016572:Cyclosporine / Q000009:adverse effects; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D003967:Diarrhea / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D057915:Drug Substitution; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives; D028321:Plant Preparations / Q000009:adverse effects; D016016:Proportional Hazards Models; D012307:Risk Factors; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D029757:Tripterygium; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D028321:Plant Preparations; D016572:Cyclosporine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D009173:Mycophenolic Acid; D016559:Tacrolimus