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特立氟胺相关性尿石症:其促尿酸排泄作用引发的一种新的不良反应。

Teriflunomide-associated urolithiasis: a new adverse reaction explained by its uricosuric effect.

机构信息

CHRU de Tours, Service de Pharmacosurveillance, Centre Régional de Pharmacovigilance Centre-Val de Loire, Tours, France.

Cabinet de Médecine générale, Saint-Martin-Le-Beau, France.

出版信息

Fundam Clin Pharmacol. 2021 Oct;35(5):930-932. doi: 10.1111/fcp.12647. Epub 2021 Mar 6.

Abstract

In clinical trials, few investigations have been conducted to determine the mechanism involved in teriflunomide-associated kidney stone formation. We report the first case of recurrent teriflunomide-induced uric acid urolithiasis. A 55-year-old man with relapsing-remitting multiple sclerosis experienced three occurrences of urolithiasis several months after the initiation of teriflunomide. While serum uric acid remained stable at 280 mmol/L, 24-h urine uric acid was increased to 2195 mmol/24 h. For the third episode, computed tomography showed three bladder stones and one stone in the right calyceal group. Endovesical lithotripsy was used to extract four orange-colored stones of more than 20 mm. Stone analysis exhibited morphology subtype IIIb with 100% of anhydrous uric acid. Given the disease control, teriflunomide was continued. After urinary alkalinization by potassium citrate, the patient remained asymptomatic at 18 months follow-up. An inhibitory effect of dihydroorotate and/or teriflunomide on urate tubular reabsorption could explain teriflunomide-associated uric acid urolithiasis. This case in a patient without risk factors suggests that multiple sclerosis patients may be at greater risk of forming uric acid urinary stones when taking teriflunomide. Alkalinization of the urine may reduce the risk of recurrence, allowing further treatment with teriflunomide.

摘要

在临床试验中,很少有研究旨在确定与特立氟胺相关的肾结石形成的机制。我们报告首例复发性特立氟胺诱导的尿酸尿结石。一位 55 岁男性患有复发性缓解型多发性硬化症,在开始使用特立氟胺后几个月内发生了三次尿结石。虽然血清尿酸保持在 280mmol/L 稳定,但 24 小时尿液尿酸增加到 2195mmol/24h。第三次发作时,计算机断层扫描显示三个膀胱结石和一个右肾盏组的结石。经尿道膀胱碎石术用于提取四个超过 20mm 的橙色结石。结石分析显示形态亚型 IIIb,无水尿酸含量为 100%。考虑到疾病控制,继续使用特立氟胺。在枸橼酸钾碱化尿液后,患者在 18 个月的随访中仍无症状。二氢乳清酸和/或特立氟胺对尿酸肾小管重吸收的抑制作用可能解释了特立氟胺相关的尿酸尿结石。在没有危险因素的患者中出现这种情况表明,多发性硬化症患者在服用特立氟胺时可能有更高的形成尿酸尿结石的风险。尿液碱化可能降低复发风险,从而允许进一步使用特立氟胺治疗。

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