title: Pre-transplant inosine monophosphate dehydrogenase activity is associated with clinical outcome after renal transplantation.
abstract: Mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase (IMPDH) activity, is usually administered as a standard dose of 1 g b.i.d. after renal transplantation. Because MMF dose reductions are associated with inferior outcome, we investigated pre-transplant IMPDH activity, MMF dose reductions and outcome. IMPDH activity was determined in isolated peripheral mononuclear cells immediately prior to renal transplantation. We observed considerable inter-individual variability in pre-transplant IMPDH activity (9.35 +/- 4.22 nmol/mg/h). Thirty of 48 patients (62.5%) with standard MMF dose (1 g b.i.d.) had dose reductions within 3 years post-transplant; these patients also had significantly lower IMPDH activity. The area under the receiver-operating characteristics curve (AUC-ROC) for prediction of dose reduction within 6 months post-transplant was 0.75 (95% CI, 0.61-0.89; p < 0.004). IMPDH activity above the cut-off value, MMF dose reduction and age of recipient were significant contributors for the occurrence of acute rejection in the multivariate logistic regression. Patients with high IMPDH activity and MMF dose reduction had the highest rejection rate (81.8% vs. 36.4%; p < 0.01).
  
  
  CONCLUSIONS
  Patients with low IMPDH activity experienced more complications of MMF therapy. High pre-transplant IMPDH activity and MMF dose reductions were associated with rejection. Determination of IMPDH activity prior to transplantation may help to improve MMF therapy after renal transplantation.
authors.affiliation: Department of Internal Medicine-Nephrology, Charite Campus Mitte, Humboldt University, Berlin, Germany. petra.glander@charite.de
authors.forename: Petra
authors.initials: P
authors.lastname: Glander
authors.forename: Pia
authors.initials: P
authors.lastname: Hambach
authors.forename: Kay-Patrick
authors.initials: KP
authors.lastname: Braun
authors.forename: Lutz
authors.initials: L
authors.lastname: Fritsche
authors.forename: Markus
authors.initials: M
authors.lastname: Giessing
authors.forename: Ingnid
authors.initials: I
authors.lastname: Mai
authors.forename: Gunilla
authors.initials: G
authors.lastname: Einecke
authors.forename: Johannes
authors.initials: J
authors.lastname: Waiser
authors.forename: Hans-Hellmut
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D019540:Area Under Curve; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007168:IMP Dehydrogenase / Q000097:blood*; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*; D016017:Odds Ratio; D011300:Preoperative Care; D012372:ROC Curve; D012086:Reoperation; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid