1例大剂量甲氨蝶呤化疗致急性肾损伤及甲氨蝶呤延迟排泄的病例分析

A Case Analysis of Acute Kidney Injury and Delayed Excretion of Methotrexate Caused by High-dose Methotrexate Chemotherapy

1例中枢弥漫大B细胞淋巴瘤患者入院后给予大剂量甲氨蝶呤(HD-MTX)化疗。尽管给予了充分水化、碱化及亚叶酸钙(CF)解救,患者仍出现急性肾损伤(AKI)及甲氨蝶呤(MTX)延迟排泄。临床药师参与对患者的救治过程及药学监护,提醒临床监测MTX血药浓度并根据MTX血药浓度调整CF剂量,并对患者4个MTX药物代谢基因进行检测。患者之后经大剂量CF解救、肾脏替代治疗及其他积极救治,虽然肾功能明显改善,但MTX延迟排泄改善困难,最终患者发生Ⅳ度骨髓抑制并死亡。药物代谢基因基因多态性检测结果显示患者MTHFR 1298、ABCB13435为杂合突变。此病例分析提示,HD-MTX易导致危及生命的AKI及MTX延迟排泄。充分的水化、碱化、及时进行MTX药代动力学指导的CF解救、以及对患者相关化疗风险的评估是保障HD-MTX化疗安全的重要因素。

A patient with central diffuse large B-cell lymphoma was given high-dose methotrexate(HD-MTX)chemotherapy after admission.Despite hydration,alkalization and calcium folinate(CF)rescue,the patient developed acute kidney injury(AKI)and delayed excretion of methotrexate(MTX).The clinical pharmacist participated in the treatment and pharmaceutical care of the patients.The clinical pharmacists participated in the treatment process and pharmaceutical care of the patients,reminded the clinicians to monitor the MTX blood concentration and adjust the CF dose according to the MTX blood concentration,and detect the four MTX drug metabolism genes of the patients.Afterwards,the patient received high-dose CF rescue,renal replacement therapy and other active treatments.Although the renal function was significantly improved,the delayed excretion of MTX was difficult to improve,and eventually the patient developed gradeⅣmyelosuppression and died.The results of drug metabolism gene polymorphism test showed that the patient’s MTHFR 1298 and ABCB13435 were heterozygous mutations.This case analysis suggests that HD-MTX predisposes to life-threatening AKI and delayed excretion of MTX.Adequate hydration,alkalization,timely MTX pharmacokinetic-guided CF rescue,and assessment of patient-related chemotherapy risks are important factors to ensure the safety of HD-MTX chemotherapy.