Shye Michael, Hanna Ramy M, Patel Sapna S, Tram-Tran Ngoc, Hou Jean, Mccannel Collin, Khalid Maham, Hanna Mina, Abdelnour Lama, Kurtz Ira
Department of Medicine, Division of Nephrology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
Department of Medicine, Division of Nephrology, UCI School of Medicine, Irvine, CA, USA.
Clin Kidney J. 2020 Jun 28;13(6):969-980. doi: 10.1093/ckj/sfaa049. eCollection 2020 Dec.
Systemic vascular endothelial growth factor (VEGF) inhibitions can induce worsening hypertension, proteinuria and glomerular diseases of various types. These agents can also be used to treat ophthalmic diseases like proliferative diabetic retinopathy, diabetic macular edema, central retinal vein occlusion and age-related macular degeneration. Recently, pharmacokinetic studies confirmed that these agents are absorbed at levels that result in biologically significant suppression of intravascular VEGF levels. There have now been 23 other cases published that describe renal sequela of intravitreal VEGF blockade, and they unsurprisingly mirror known systemic toxicities of VEGF inhibitors. We present three cases where stable levels of proteinuria and chronic kidney disease worsened after initiation of these agents. Two of our three patients were biopsied. The first patient's biopsy showed diabetic nephropathy and focal and segmental glomerulosclerosis (FSGS) with collapsing features and acute interstitial nephritis (AIN). The second patient's biopsy showed AIN in a background of diabetic glomerulosclerosis. This is the second patient seen by our group, whose biopsy revealed segmental glomerulosclerosis with collapsing features in the setting of intravitreal VEGF blockade. Though FSGS with collapsing features and AIN are not the typical lesions seen with systemic VEGF blockade, they have been reported as rare case reports previously. In addition to reviewing known elements of intravitreal VEGF toxicity, the cases presented encompass renal pathology data supporting that intravitreal VEGF blockade can result in deleterious systemic and renal pathological disorders.
全身血管内皮生长因子（VEGF）抑制可导致高血压恶化、蛋白尿及各类肾小球疾病。这些药物还可用于治疗眼科疾病，如增殖性糖尿病视网膜病变、糖尿病黄斑水肿、视网膜中央静脉阻塞和年龄相关性黄斑变性。最近，药代动力学研究证实，这些药物的吸收水平可导致血管内VEGF水平受到具有生物学意义的抑制。目前已有23例其他病例报道描述了玻璃体内VEGF阻断的肾脏后遗症，不出所料，它们反映了已知的VEGF抑制剂的全身毒性。我们报告了3例在开始使用这些药物后蛋白尿水平稳定及慢性肾病恶化的病例。我们的3例患者中有2例接受了活检。首例患者的活检显示为糖尿病肾病、具有塌陷特征的局灶节段性肾小球硬化（FSGS）及急性间质性肾炎（AIN）。第二例患者的活检显示在糖尿病肾小球硬化背景下存在AIN。这是我们团队所见的第二例患者，其活检显示在玻璃体内VEGF阻断的情况下存在具有塌陷特征的节段性肾小球硬化。尽管具有塌陷特征的FSGS和AIN并非全身VEGF阻断所见的典型病变，但此前已有罕见病例报道。除了回顾玻璃体内VEGF毒性的已知因素外，所呈现的病例还包含肾脏病理数据，支持玻璃体内VEGF阻断可导致有害的全身和肾脏病理紊乱。
