Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Ren Fail. 2021 Dec;43(1):335-339. doi: 10.1080/0886022X.2021.1874985.
The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 μmol/L to 125 μmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.
布鲁顿酪氨酸激酶抑制剂伊布替尼的引入在慢性淋巴细胞白血病和其他 B 细胞恶性肿瘤的治疗方面取得了重大进展。由于细胞因子释放减少，它在慢性移植物抗宿主病中有效，并且在自身免疫性疾病和预防 COVID-19 相关肺损伤中也建议使用。尽管对免疫反应有这种影响，但我们报告了一名 76 岁男性患者在诊断为幼淋巴细胞白血病后出现严重过敏反应。伊布替尼开始后 4 周，出现非少尿性急性肾损伤，伴有蛋白尿和镜下血尿，伴有下肢紫癜和感觉异常。肾活检显示急性间质性肾炎。给予 1mg/kg 甲基强的松龙治疗后，患者的血清肌酐从 365μmol/L 降至 11 天的 125μmol/L，蛋白尿血尿和紫癜、感觉异常得到缓解。3 个月后，在 eGFR 稳定为 56ml/min/1.73m 的情况下，停用甲基强的松龙，并开始使用利妥昔单抗 venetoclax 治疗，无副作用。我们得出结论，尽管伊布替尼对 Th1 方向的细胞因子反应有有益影响，但它可引起急性间质性肾炎。早期发现、停用伊布替尼、给予糖皮质激素可能有助于更好地保留肾功能，从而降低潜在后续肾损伤的风险。
