Abstract：
BACKGROUND: Combined treatment with dabrafenib, a B-RAF inhibitor, and trametinib, a mitogen-activated protein kinase inhibitor, is an effective option for patients with metastatic melanoma. A few cases of acute kidney injury associated with tubulointerstitial nephritis and 1 case of nephrotic syndrome have been reported in patients on this drug combination; however, progressive renal injury has not been reported. In this case study, we report a patient with metastatic melanoma who developed glomerular capillary endothelial toxicity and progressive glomerular sclerosis during combination therapy.
METHODS: Our patient was an 80-year-old woman with a history of type 2 diabetes and chronic kidney disease.
METHODS: She was diagnosed with metastatic melanoma and commenced combination therapy with dabrafenib and trametinib.
RESULTS: Her renal function progressively deteriorated; by month 20 after treatment commencement, her serum creatinine level had increased from 1.59 to 3.74 mg/dL. The first kidney biopsy revealed marked glomerular and endothelial cell damage. Her medication was stopped, but no improvement was evident. At 5 months after the first biopsy, her serum creatinine level had increased to 5.46 mg/dL; a second kidney biopsy revealed focal segmental glomerular sclerosis and marked tubulointerstitial fibrosis. She was started on hemodialysis.
CONCLUSIONS: We describe a patient with a metastatic melanoma who developed progressive kidney failure during treatment with dabrafenib and trametinib. The most prominent microscopy findings were glomerular endothelial damage in the initial kidney biopsy and accelerated glomerular sclerosis and tubulointerstitial fibrosis in the follow-up biopsy. We hypothesize that a decreased renal reserve and impairment of kidney repair capacity caused by inhibition of B-RAF, a downstream mediator of vascular endothelial growth factor, may explain the progressive kidney injury.
METHODS: Our patient was an 80-year-old woman with a history of type 2 diabetes and chronic kidney disease.
METHODS: She was diagnosed with metastatic melanoma and commenced combination therapy with dabrafenib and trametinib.
RESULTS: Her renal function progressively deteriorated; by month 20 after treatment commencement, her serum creatinine level had increased from 1.59 to 3.74 mg/dL. The first kidney biopsy revealed marked glomerular and endothelial cell damage. Her medication was stopped, but no improvement was evident. At 5 months after the first biopsy, her serum creatinine level had increased to 5.46 mg/dL; a second kidney biopsy revealed focal segmental glomerular sclerosis and marked tubulointerstitial fibrosis. She was started on hemodialysis.
CONCLUSIONS: We describe a patient with a metastatic melanoma who developed progressive kidney failure during treatment with dabrafenib and trametinib. The most prominent microscopy findings were glomerular endothelial damage in the initial kidney biopsy and accelerated glomerular sclerosis and tubulointerstitial fibrosis in the follow-up biopsy. We hypothesize that a decreased renal reserve and impairment of kidney repair capacity caused by inhibition of B-RAF, a downstream mediator of vascular endothelial growth factor, may explain the progressive kidney injury.
摘要：
背景：dabrafenib联合治疗，B-RAF抑制剂,和曲美替尼，丝裂原活化蛋白激酶抑制剂，是转移性黑色素瘤患者的有效选择。据报道，在这种药物组合的患者中，有几例与肾小管间质性肾炎相关的急性肾损伤和1例肾病综合征；然而，进行性肾损伤尚未有报道.在这个案例研究中,我们报道1例转移性黑色素瘤患者在联合治疗期间出现肾小球毛细血管内皮毒性和进行性肾小球硬化.
方法：我们的患者是一名80岁女性，有2型糖尿病和慢性肾脏疾病病史。
方法：患者被诊断为转移性黑色素瘤，开始接受达拉非尼和曲美替尼联合治疗。
结果：她的肾功能逐渐恶化，治疗开始后20个月，她的血清肌酐水平从1.59mg/dL升高至3.74mg/dL.首次肾活检显示肾小球和内皮细胞明显受损。她停药了,但没有明显的改善。第一次活检后5个月，她的血清肌酐水平增加至5.46mg/dL;第二次肾活检显示局灶性节段肾小球硬化和明显的肾小管间质纤维化.她开始接受血液透析。
结论：我们描述了一名患有转移性黑色素瘤的患者，在接受达拉非尼和曲美替尼治疗期间出现进行性肾衰竭。最突出的显微镜检查结果是最初的肾活检中的肾小球内皮损伤和后续活检中的肾小球硬化和肾小管间质纤维化加速。我们假设抑制B-RAF引起的肾脏储备减少和肾脏修复能力受损，血管内皮生长因子的下游介质，可以解释进行性肾损伤。
方法：我们的患者是一名80岁女性，有2型糖尿病和慢性肾脏疾病病史。
方法：患者被诊断为转移性黑色素瘤，开始接受达拉非尼和曲美替尼联合治疗。
结果：她的肾功能逐渐恶化，治疗开始后20个月，她的血清肌酐水平从1.59mg/dL升高至3.74mg/dL.首次肾活检显示肾小球和内皮细胞明显受损。她停药了,但没有明显的改善。第一次活检后5个月，她的血清肌酐水平增加至5.46mg/dL;第二次肾活检显示局灶性节段肾小球硬化和明显的肾小管间质纤维化.她开始接受血液透析。
结论：我们描述了一名患有转移性黑色素瘤的患者，在接受达拉非尼和曲美替尼治疗期间出现进行性肾衰竭。最突出的显微镜检查结果是最初的肾活检中的肾小球内皮损伤和后续活检中的肾小球硬化和肾小管间质纤维化加速。我们假设抑制B-RAF引起的肾脏储备减少和肾脏修复能力受损，血管内皮生长因子的下游介质，可以解释进行性肾损伤。
