Despite optimal anticoagulation and blood pressure control, patients with antiphospholipid syndrome (APS) nephropathy frequently progress to kidney failure, and recurrence after transplantation is common. The mTORC (mechanistic target of rapamycin complex) pathway was recently identified as a potential intermediate and a therapeutic target in vascular lesions associated with APS nephropathy. However, these results were derived from the retrospective analysis of a small cohort of patients receiving sirolimus after kidney transplantation. Therefore, they warranted external validation and the demonstration of the potential benefit of sirolimus in native kidney APS nephropathy. We report a patient with active APS nephropathy lesions occurring on native kidneys, in which endothelial mTORC activation was substantiated at the molecular level. Treatment with sirolimus was shown on a repeat kidney biopsy to successfully inhibit the AKT/mTORC pathway and was associated with significant improvement in kidney function and lesions of vasculopathy. Drug tolerance was excellent during the entire follow-up. This case validates and extends previous observations in kidney transplant recipients and demonstrates that endothelial activation of the AKT/mTORC pathway occurs in the damaged renal vasculature of native kidneys in APS nephropathy. These findings further support the potential of precision medicine and the use of mTORC activation as a biomarker of disease activity and as therapeutic target in patients with APS nephropathy.

尽管有最佳的抗凝和血压控制，但抗磷脂综合征（APS）肾病患者经常会发展为肾功能衰竭，并且移植后复发很常见。最近发现，mTORC（雷帕霉素复合物的机械靶标）途径是与APS肾病相关的血管病变的潜在中间体和治疗靶标。然而，这些结果来自对肾移植后接受西罗莫司治疗的一小部分患者的回顾性分析。因此，他们需要进行外部验证，并证明西罗莫司在天然肾脏APS肾病中具有潜在的益处。我们报告一名患者发生在天然肾脏上的活动性APS肾病病变，其中在分子水平上证实了内皮mTORC激活。西罗莫司的治疗在重复的肾脏活检中显示可成功抑制AKT / mTORC途径，并与肾脏功能和血管病变的显着改善相关。在整个随访过程中，药物耐受性都非常好。该病例证实并扩展了先前在肾脏移植受者中的观察结果，并证明了AKT / mTORC途径的内皮细胞活化发生在APS肾病中天然肾脏的受损肾血管中。这些发现进一步支持了精密医学的潜力以及mTORC激活作为APS肾病患者疾病活动的生物标志物和治疗靶标的用途。