Clin Nephrol. 2021 Apr;95(4):215-220. doi: 10.5414/CN110392.
Common side effects of mycophenolate mofetil (MMF) are diarrhea, leukopenia, and infectious complication. The polymorphisms of enzymes affecting MMF clearance could be related to MMF toxicity, and in vitro study revealed that high MMF levels might cause endothelial dysfunction. A 7-year-old Korean male with end-stage renal disease on peritoneal dialysis due to mesangial proliferative glomerulonephritis received a kidney transplantation (KT) from a deceased donor, and immunosuppressive medications including MMF, tacrolimus, and methylprednisolone were started after KT. The patient developed oliguria immediately after surgery, and therapeutic plasmapheresis was initiated with continuous renal replacement therapy for the possibility of graft dysfunction and nephrotic syndrome relapse. Renal function recovered 4 days later, but the patient developed ascites. Diagnostic paracentesis revealed findings that were interpreted as uncomplicated ascites in cirrhosis, not of renal origin. Abdominal ultrasonography showed increased parenchymal echogenicity without cirrhotic change in the liver. Based on a case report and differential diagnosis, we replaced MMF with azathioprine, and 4 weeks later a sudden increment in urine output was detected. Eleven months after KT, the patient is free from ascites. The 802 polymorphism was tested, and wild-type 802 was detected, which is related to low MMF clearance. The low clearance of MMF by 802 wild-type polymorphism might have led to MMF toxicity affecting endothelial dysfunction. This case suggests that refractory ascites could be induced by MMF, and endothelial damage is a possible mechanism.
霉酚酸酯(MMF)的常见副作用有腹泻、白细胞减少和感染并发症。影响 MMF 清除率的酶的多态性可能与 MMF 毒性有关,体外研究表明,高 MMF 水平可能导致内皮功能障碍。一名 7 岁韩国男性因系膜增生性肾小球肾炎行腹膜透析治疗,终末期肾病,接受了一名已故供体的肾移植(KT),KT 后开始使用包括 MMF、他克莫司和甲基强的松龙在内的免疫抑制剂。患者手术后立即出现少尿,并开始进行治疗性血浆置换和持续肾脏替代治疗,以排除移植物功能障碍和肾病综合征复发的可能。肾功能在 4 天后恢复,但患者出现腹水。诊断性腹腔穿刺显示为肝硬化非肾源性单纯性腹水。腹部超声显示肝脏实质回声增强,无肝硬化改变。根据病例报告和鉴别诊断,我们将 MMF 替换为硫唑嘌呤,4 周后检测到尿量突然增加。KT 后 11 个月,患者腹水已消失。对 802 多态性进行了检测,检测到野生型 802,与 MMF 清除率低有关。802 野生型 MMF 清除率低可能导致 MMF 毒性影响内皮功能障碍。本病例提示 MMF 可能导致难治性腹水,内皮损伤可能是其发病机制之一。