Hanna Ramy M, Yanny Beshoy, Arman Farid, Barsoum Marina, Mikhail Mira, Al Baghdadi Maha, Rastogi Anjay, Wallace William, Saab Sammy
Department of Medicine, Division of Nephrology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA.
Department of Medicine, Division of Digestive Disease, Hepatology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA.
Saudi J Kidney Dis Transpl. 2019 Jul-Aug;30(4):989-994. doi: 10.4103/1319-2442.265481.
Mammalian target of rapamycin (mTOR) inhibitors are used in renal sparing protocols and transplant immunosuppression in patients with solid organ and stem cell transplants. They cause various side effects, including proteinuria, which is mediated by blockade of the vascular endothelial growth factor receptor pathway. There have been various reports of mTOR inhibitors causing proteinuria or worsening proteinuria form preexisting renal glomerulo-pathies. We report a 73-year old male with diabetic glomerulosclerosis, acute liver failure due to Budd-Chiari syndrome, chronic low platelets, and worsening proteinuria from 0.46 g protein/g creatinine to 2.2 g protein/g creatinine. Workup revealed no thrombotic microangiopathy through skin biopsy, and a renal biopsy confirmed only clinically suspected diabetic and hypertensive glomerulosclerosis and possible calcineurin inhibitors. On discontinuation of everolimus urine protein decreased back to 0.6 g/g creatinine. We review the mechanism of mTOR-induced proteinuria and how this may affect diabetic nephropathy secondarily. We also consider the clinical implications of this in transplant patients receiving these agents.
雷帕霉素哺乳动物靶点（mTOR）抑制剂用于实体器官和干细胞移植患者的肾脏保护方案及移植免疫抑制。它们会引起各种副作用，包括蛋白尿，这是由血管内皮生长因子受体途径的阻断介导的。已有各种关于mTOR抑制剂导致蛋白尿或使先前存在的肾小球疾病的蛋白尿恶化的报道。我们报告了一名73岁男性，患有糖尿病性肾小球硬化症、布加综合征所致急性肝衰竭、慢性血小板减少，蛋白尿从0.46克蛋白质/克肌酐恶化至2.2克蛋白质/克肌酐。检查通过皮肤活检未发现血栓性微血管病，肾活检仅证实临床怀疑的糖尿病和高血压性肾小球硬化症以及可能的钙调神经磷酸酶抑制剂。停用依维莫司后，尿蛋白降至0.6克/克肌酐。我们回顾了mTOR诱导蛋白尿的机制以及这可能如何继发影响糖尿病肾病。我们还考虑了这对接受这些药物的移植患者的临床意义。
