肾功能和肝功能对外周血单核细胞和尿嘧啶血症中二氢嘧啶脱氢酶表型的影响。

IF 3.7 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY
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

摘要

目的:探讨尿嘧啶血症(U)与外周血单个核细胞(PBMC)二氢嘧啶脱氢酶(DPD)活性的关系及其是否受肾功能或肝功能损害的影响。方法:本回顾性研究纳入176例癌症患者,进行治疗前U (UPLC-MSMS法)和pmc - dpd(放射性酶测定法)分析(常规表型)。血肾(肌酐,BUN)和肝(ALT, AST, GGT, ALP,白蛋白,胆红素)检查在DPD表型前15天或DPD表型后4天内进行。生化指标按CTCAEv5.0级(G)进行分类。评估肾小球滤过率(eGFR) (CKD-EPI和EKFC)。采用非参数统计检验。结果:以PBMC-DPD(即≤100 pmol/min/mg)为标准,部分缺乏率为3.4 %;以U(即≥16 μg/L)为标准,部分缺乏率为6.3 %。未观察到完全缺陷。176例患者中有15例(8.5 %)表现出PBMC活性和U之间的DPD状态不一致。PBMC-DPD和U之间的相关性显著但较弱(r= -0.309, p1-UNL, p=0.009), GGT (G0 vs. G1 vs. G2 vs. G3, p)。结论:尚不清楚肾脏和/或肝脏损害是否作为影响尿毒症检测准确性的混杂因素,或者是否真正影响DPD活性,建议谨慎解释U。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impact of renal and hepatic function on dihydropyrimidine dehydrogenase phenotype assessed by enzyme activity in peripheral blood mononuclear cells and uracilemia.

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.

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来源期刊
Clinical chemistry and laboratory medicine
Clinical chemistry and laboratory medicine 医学-医学实验技术
CiteScore
11.30
自引率
16.20%
发文量
306
审稿时长
3 months
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. CCLM is the official journal of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and publishes regularly EFLM recommendations and news. CCLM is the official journal of the National Societies from Austria (ÖGLMKC); Belgium (RBSLM); Germany (DGKL); Hungary (MLDT); Ireland (ACBI); Italy (SIBioC); Portugal (SPML); and Slovenia (SZKK); and it is affiliated to AACB (Australia) and SFBC (France). 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 Follow @cclm_degruyter on Twitter!
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