Gaible Clotilde, Narjoz Céline, Loriot Marie-Anne, Roueff Stéphane, Pallet Nicolas
Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, University of Paris, Paris, France.
Service de Biochimie, Department of Clinical Chemistry, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, University of Paris, 75015, Paris, France.
Cancer Chemother Pharmacol. 2021 Dec;88(6):1049-1053. doi: 10.1007/s00280-021-04354-7. Epub 2021 Sep 13.
Pretherapeutic screening for dihydropyrimidine dehydrogenase (DPD) deficiency is recommended prior to the administration of fluoropyrimidine-based chemotherapy. However, the best strategy to identify DPD deficiency in End Stage Renal Disease (ESRD) patients is unknown.
We assessed the characteristics of both DPD phenotypes and DPYD genotypes in 20 dialyzed patients before and after dialysis session. The extent to which the concentrations of uracil [U] and dihydrouracil [UH] were affected by dialysis was evaluated.
Mean [U] was 14 ± 3.3 ng/ml before the dialysis session, and 7.9 ± 2.7 ng/ml after. Notably, mean [U] in 119 non-ESRD patients during the same timeline was 8.7 ± 3.9 ng/ml, which is similar to [U] values after dialysis session (p = 0.38). [U] values > 16 ng/ml were measured in 4 ESRD patients (20%), whereas the rate was 3.3% in the non-ESRD cohort. Whole gene sequencing did not reveal DPYD deleterious allelic variants in the 4 ESRD patients with [U] values > 16 ng/ml. The profile of [UH2] values during dialysis was similar to that of [U]: 385 ± 86 ng/ml before, and 185 ± 62 ng/ml after (mean reduction rate 42.5%). Thus, [UH2]:[U] ratio remained unaffected by dialysis, and was similar to the values in non-ESRD patients (22.4 ± 7.1).
Phenotyping based on measuring plasma [U] before a dialysis sessions in ESRD patients is associated with an unacceptable high rate of false positives. The optimal strategy for the identification of patients with DPD deficiency in this population would be the monitor the [UH]:[U] ratio, which remains unaffected.
在给予氟嘧啶类化疗药物之前，建议对二氢嘧啶脱氢酶（DPD）缺乏症进行治疗前筛查。然而，识别终末期肾病（ESRD）患者中DPD缺乏症的最佳策略尚不清楚。
我们评估了20例透析患者透析前后DPD表型和DPYD基因型的特征。评估了透析对尿嘧啶[U]和二氢尿嘧啶[UH]浓度的影响程度。
透析前平均[U]为14±3.3 ng/ml，透析后为7.9±2.7 ng/ml。值得注意的是，在同一时间段内，119例非ESRD患者的平均[U]为8.7±3.9 ng/ml，与透析后的[U]值相似（p = 0.38）。4例ESRD患者（20%）的[U]值>16 ng/ml，而非ESRD队列中的这一比例为3.3%。对4例[U]值>16 ng/ml的ESRD患者进行全基因测序，未发现DPYD有害等位基因变异。透析期间[UH2]值的变化情况与[U]相似：透析前为385±86 ng/ml，透析后为185±62 ng/ml（平均降低率42.5%）。因此，[UH2]:[U]比值不受透析影响，与非ESRD患者的值相似（22.4±7.1）。
基于在ESRD患者透析前测量血浆[U]进行表型分析会出现不可接受的高假阳性率。识别该人群中DPD缺乏症患者的最佳策略是监测[UH]:[U]比值，该比值不受影响。
