Impact of renal and hepatic function on dihydropyrimidine dehydrogenase phenotype assessed by enzyme activity in peripheral blood mononuclear cells and uracilemia.
Sara Contu, Manon Launay, Hélène Bouges Le Royer, Laurence Simon, Audrey Mignot, Eva Seutin, Renaud Schiappa, Philippe Follana, Anne Creisson, Ludovic Evesque, Marie-Christine Etienne-Grimaldi
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引用次数: 0
Abstract
Objectives: To investigate the relationship between uracilemia (U) and dihydropyrimidine dehydrogenase (DPD) activity in peripheral blood mononuclear cells (PBMC) and whether they are influenced by renal or hepatic impairment.
Methods: This retrospective study included 176 cancer patients with pre-treatment U (UPLC-MSMS assay) and PBMC-DPD (radioenzymatic assay) analyzed the same day (routine phenotyping). Blood renal (creatinine, BUN) and hepatic (ALT, AST, GGT, ALP, albumin, bilirubin) work-up was performed within 15 days before or up to 4 days after DPD phenotyping. Biochemical markers were categorized according to CTCAEv5.0 grade (G). Glomerular filtration rate (eGFR) was estimated (CKD-EPI and EKFC). Non-parametric statistical tests were used.
Results: Prevalence of partial deficiency was 3.4 % based on PBMC-DPD (i.e. ≤100 pmol/min/mg) and 6.3 % based on U (i.e. ≥16 μg/L). No complete deficiency was observed. Fifteen patients out of 176 (8.5 %) exhibited discordant DPD status between PBMC activity and U. The correlation between PBMC-DPD and U was significant but weak (r= -0.309, p<0.001). PBMC-DPD (mean 246, median 235, range 62-926 pmol/min/mg prot) was not influenced by renal or hepatic impairment. U (mean 9.6, median 8.5, range 1.7-57.8 μg/L) was significantly higher in patients with elevated BUN (normal vs. >1-UNL, p=0.009), GGT (G0 vs. G1 vs. G2 vs. G3, p<0.001), AST (G0 vs. G≥1, p=0.015), or with hypoalbuminemia (G0 vs. G ≥ 1, p=0.045). Categorized creatinine or eGFR did not influence U.
Conclusions: It remains unclear whether renal and/or hepatic impairment acts as a confounding factor affecting the accuracy of uracilemia testing, or whether truly impacts DPD activity, suggesting caution in U interpretation.
期刊介绍:
Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor over 3. CCLM is issued monthly, and it is published in print and electronically.
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Topics:
- clinical biochemistry
- clinical genomics and molecular biology
- clinical haematology and coagulation
- clinical immunology and autoimmunity
- clinical microbiology
- drug monitoring and analysis
- evaluation of diagnostic biomarkers
- disease-oriented topics (cardiovascular disease, cancer diagnostics, diabetes)
- new reagents, instrumentation and technologies
- new methodologies
- reference materials and methods
- reference values and decision limits
- quality and safety in laboratory medicine
- translational laboratory medicine
- clinical metrology
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