Inosine Monophosphate Dehydrogenase Messenger RNA Expression Is Correlated to Clinical Outcomes in Mycophenolate Mofetil-Treated Kidney Transplant Patients, Whereas Inosine Monophosphate Dehydrogenase Activity Is Not

2009 ◽  
Vol 31 (5) ◽  
pp. 549-556 ◽  
Author(s):  
Ferdi Sombogaard ◽  
Annemiek M A Peeters ◽  
Carla C Baan ◽  
Ron A A Mathot ◽  
Monique E Quaedackers ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Dehydrogenase Activity ◽  
Kidney Transplant ◽  
Messenger Rna ◽  
Rna Expression ◽  
Inosine Monophosphate Dehydrogenase ◽  
Inosine Monophosphate ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Monophosphate Dehydrogenase

Mycophenolate mofetil, an inhibitor of inosine monophosphate dehydrogenase, causes a paradoxical elevation of GTP in erythrocytes of renal transplant patients

2004 ◽  
Vol 107 (1) ◽  
pp. 63-68 ◽  
Author(s):  
David GOLDSMITH ◽  
Elizabeth A. CARREY ◽  
Stephen EDBURY ◽  
Ryszard T. SMOLENSKI ◽  
Piotr. JAGODZINSKI ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Renal Transplantation ◽  
Renal Transplant ◽  
Plasma Metabolites ◽  
Renal Transplant Recipients ◽  
Inosine Monophosphate Dehydrogenase ◽  
Inosine Monophosphate ◽  
Transplant Patients ◽  
Renal Transplant Patients ◽  
Monophosphate Dehydrogenase

The immunosuppressant MMF (mycophenolate mofetil) has increasingly replaced AZA (azathioprine) in renal transplantation. MMF is a prodrug of MPA (mycophenolic acid), which inhibits lymphocyte IMPDH (inosine monophosphate dehydrogenase), thereby drastically decreasing GTP concentrations essential to lymphocyte proliferation in vitro and in vivo. Erythrocyte GTP concentrations are commonly elevated in severe renal disease, but normalize following successful engraftment. Consequently, elevated GTP in renal transplant recipients might signal impending loss of immunosuppression and graft failure. In the present study, we compared erythrocyte nucleotides and plasma metabolites in two groups of 25 patients after renal transplantation, both receiving prednisolone and cyclosporin A, but one group receiving MMF and the other AZA. No patients had recent allograft biopsy evidence of rejection. Erythrocyte GTP concentrations at MMF commencement were 50.4±23.4 μmol/l. An increase occurred during the first 3 months after transplant when MMF was used de novo, stabilizing at 146.7±62.9 μmol/l after 4 months. This was significantly higher (P=2.5×10−6) than erythrocyte GTP (40.4±15.9 μmol/l) in the AZA group, which was essentially unchanged from values immediately after successful transplantation. The effect of MMF on erythrocyte GTP levels was reversible, since GTP levels fell when MMF therapy was terminated. The results demonstrate paradoxically high GTP concentrations in erythrocytes of renal transplant patients receiving MMF. MPA may stabilize reticulocyte IMPDH, allowing the protein to persist during erythropoiesis. This behaviour is in marked contrast with the decrease in GTP levels seen in white blood cells of patients on chronic MMF therapy.

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