Division of Nephrology and Hypertension, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
BMC Nephrol. 2022 Oct 29;23(1):348. doi: 10.1186/s12882-022-02986-2.
Vascular endothelial growth factor inhibitors (VEGFIs) are used to treat malignant neoplasms and ocular diseases by inhibiting angiogenesis. Systemic use of VEGFIs has various side effects, including hypertension, proteinuria, and thrombotic microangiopathy, but adverse events due to intravitreal injection of VEGFIs have not been fully clarified. Although age-related macular degeneration was initially the most common target of intravitreal injection of VEGFIs, it has also been applied sporadically for diabetic macular edema in recent years. Proteinuria following intravitreal injection of VEGFIs would be reversible. In patients with diabetes mellitus (DM), however, it would be difficult to determine whether kidney damage arises from the clinical course of DM or from intravitreal injection of VEGFIs for diabetic macular edema.
A 55-year-old woman with a 20-year history of type 2 DM began intravitreal injection of VEGFI (aflibercept, 2 mg every 4 weeks) for treatment of diabetic macular edema 2 years previously. She presented with leg edema, hypertension, and nephrotic-range proteinuria 14 months after the first injection. Histological examination of renal biopsy specimens revealed diabetic nephropathy with renal thrombotic microangiopathy probably associated with intravitreal injection of VEGFI. The patient's nephrotic syndrome completely improved at 6 months after simply discontinuing aflibercept.
This is a precious report of pathologically investigated renal thrombotic microangiopathy leading to nephrotic syndrome due to intravitreal injection of aflibercept for diabetic macular edema in a patient with type 2 DM. Renal function and proteinuria should be monitored in diabetic patients who receive intravitreal injection of a VEGFI. If kidney damage develops independent of the clinical course of DM during intravitreal injection of a VEGFI, renal biopsy should be performed and intravitreal VEGFI injection discontinued.
血管内皮生长因子抑制剂 (VEGFIs) 通过抑制血管生成来治疗恶性肿瘤和眼部疾病。VEGFIs 的全身使用有各种副作用，包括高血压、蛋白尿和血栓性微血管病，但玻璃体腔内注射 VEGFIs 的不良反应尚未完全阐明。虽然年龄相关性黄斑变性最初是玻璃体腔内注射 VEGFIs 的最常见靶点，但近年来也偶尔用于糖尿病性黄斑水肿。玻璃体腔内注射 VEGFIs 后出现的蛋白尿是可逆的。然而，在糖尿病患者中，很难确定肾脏损伤是来自糖尿病的临床过程，还是来自玻璃体腔内注射 VEGFIs 治疗糖尿病性黄斑水肿。
一名 55 岁女性，患有 20 年 2 型糖尿病史，2 年前开始因糖尿病性黄斑水肿每 4 周玻璃体腔内注射 VEGFI（阿柏西普，2mg）。首次注射后 14 个月，她出现下肢水肿、高血压和肾病范围蛋白尿。肾活检组织学检查显示糖尿病肾病合并可能与玻璃体腔内注射 VEGFI 相关的肾血栓性微血管病。停用阿柏西普后 6 个月，患者的肾病综合征完全缓解。
这是一份关于 2 型糖尿病患者因玻璃体腔内注射阿柏西普治疗糖尿病性黄斑水肿而导致肾血栓性微血管病引起肾病综合征的经病理检查证实的珍贵报告。接受玻璃体腔内注射 VEGFI 的糖尿病患者应监测肾功能和蛋白尿。如果在玻璃体腔内注射 VEGFI 期间发生与 DM 临床过程无关的肾损伤，应进行肾活检并停止玻璃体腔内 VEGFI 注射。
