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Pre‐Transplant Inosine Monophosphate Dehydrogenase Activity is Associated with Clinical Outcome After Renal Transplantation
Author(s) -
Glander Petra,
Hambach Pia,
Braun KayPatrick,
Fritsche Lutz,
Giessing Markus,
Mai Ingnid,
Einecke Gunilla,
Waiser Johannes,
Neumayer HansHellmut,
Budde Klemens
Publication year - 2004
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00617.x
Subject(s) - imp dehydrogenase , medicine , transplantation , mycophenolate , mycophenolic acid , pharmacology , inosine monophosphate , urology , gastroenterology , biochemistry , chemistry , nucleotide , gene
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). Conclusion: 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.