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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-10-16
pubmed:abstractText
Measurement of the pharmacodynamic biomarker inosine monophosphate dehydrogenase (IMPDH) activity in renal transplant recipients has been proposed to reflect the biological effect better than using pharmacokinetic parameters to monitor mycophenolate mofetil therapy. The IMPDH assays are however labor intensive and this complicates implementation into patient care. Quantification of IMPDH messenger RNA (mRNA) could form an attractive alternative. This study was designed to correlate IMPDH mRNA levels with IMPDH activity and clinical outcome in renal transplant recipients. From a cohort of 101 renal transplant patients, blood samples were drawn pre transplantation and at 4 times after transplantation. IMPDH activity, IMPDH type 1 and type 2 mRNA levels, and mycophenolic acid concentrations were measured and correlated to clinical outcomes. No correlation was found between IMPDH type 1 and type 2 mRNA levels and IMPDH activity in pre- and posttransplant samples. A significant increase in IMPDH mRNA levels was found between day 6 and day 140 after transplantation. IMPDH type 1 and type 2 mRNA levels before transplant showed a trend toward statistically significant higher levels in patients with an acute rejection (P = 0.052 and P = 0.058). After transplant, the IMPDH type 1 and type 2 mRNA levels were significantly lower in patients with an acute rejection (P = 0.026 and P = 0.007). We conclude that IMPDH mRNA levels do not correlate with IMPDH activity but are nevertheless correlated with acute rejections. Furthermore, although the regulation of the expression of the 2 isoforms is presumed to be different, in this study, the changes in the expression of type 1 mRNA closely paralleled those of type 2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1536-3694
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
549-56
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
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.
pubmed:affiliation
Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't