title: Mycophenolic Acid Metabolites Acyl-Glucuronide and Glucoside Affect the Occurrence of Infectious Complications and Bone Marrow Dysfunction in Liver Transplant Recipients.
abstract: BACKGROUND Mycophenolic acid (MPA) prodrugs are anti-proliferative immunosuppressive agents commonly used after organ transplantation. Although they are generally well tolerated by patients, adverse effects may occur. It is postulated that MPA metabolites could also contribute to these adverse effects. MATERIAL AND METHODS The objective of this study was the assessment of concentrations of total MPA and its metabolites, phenyl glucuronide (MPAG), acyl glucuronide (AcMPAG) and glucoside (GluMPA), using liquid chromatography combined with mass spectrometry (LC/MS/MS) in two groups: kidney transplant recipients and liver transplant patients. Associations of MPA and its metabolites with adverse effects were analyzed. RESULTS The study group consisted of 211 recipients of liver or kidney transplants who received immunosuppressive therapy, including MPA prodrugs. Multivariant analysis showed a positive influence of MPA on gastroenterotoxicity in kidney transplant recipients. In liver patients, gastroenterotoxicity was associated with lower MPAG concentrations. A positive influence of AcMPAG on bacterial infections in liver transplant patients was observed. In liver transplant recipients, a positive influence of MPA and a negative influence of GluMPA levels on the PLT count were revealed. MPA and its metabolites did not influence the hemoglobin levels in both groups. There were no significant relationships among MPA, its metabolites and WBC counts. CONCLUSIONS In kidney transplant recipients, total MPA trough concentration is associated with gastroenterotoxicity and its monitoring could have important role in management of gastrointestinal complications. The quantification of AcMPAG in liver recipients receiving MPA may be helpful in avoiding bacterial infections. GluMPA seems to have a toxic effect on thrombopoiesis.
authors: Department of Immunology, Transplant Medicine and Internal Diseases, Medical University of Warsaw, Transplantation Institute, Warsaw, Poland.
authors: Jolanta
authors: J
authors: Zegarska
authors: Department of Immunology, Transplant Medicine and Internal Diseases, Medical University of Warsaw, Transplantation Institute, Warsaw, Poland.
authors: Ewa
authors: E
authors: Hryniewiecka
authors: Department of Immunology, Transplant Medicine and Internal Diseases, Medical University of Warsaw, Transplantation Institute, Warsaw, Poland.
authors: Dorota
authors: D
authors: Żochowska
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors: Wlodzimierz
authors: W
authors: Tszyrsznic
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors: Radosław
authors: R
authors: Jaźwiec
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors: Agnieszka
authors: A
authors: Borowiec
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors: Emilia
authors: E
authors: Pawłowska
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors: Michał
authors: M
authors: Dadlez
authors: Department of Immunology, Transplant Medicine and Internal Diseases, Medical University of Warsaw, Transplantation Institute, Warsaw, Poland.
authors: Leszek
authors: L
authors: Pączek
mesh_terms: D000328:Adult; D001424:Bacterial Infections / Q000097:blood / Q000209:etiology*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005960:Glucosides / Q000097:blood*; D020719:Glucuronides / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood; D016559:Tacrolimus / Q000627:therapeutic use; D066027:Transplant Recipients
chemical_list: D005960:Glucosides; D020719:Glucuronides; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus