Thrombotic Microangiopathy and Acute Kidney Injury Induced After Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors VEGF Blockade-Related TMA After Intravitreal Use

Abstract

Vascular endothelial growth factor (VEGF) inhibition can cause worsening hypertension, proteinuria, chronic kidney injury, and glomerular disease. Thrombotic microangiopathy (TMA) and other nephrotic disorders have been reported with systemic VEGF blockade. These same agents are given intravitreally for age-related macular degeneration (AMD) and diabetic retinopathy (DR), albeit at lower doses than those given for systemic indications. Systemic absorption of anti-VEGF agents when given intravitreally has been shown consistently along with evidence of significant intravascular VEGF suppression. While worsening hypertension has only been seen in some large-scale studies, case reports show worsening proteinuria and diverse glomerular diseases. These include TMA-associated lesions like focal and segmental glomerulosclerosis with collapsing features (cFSGS). In this paper, we report three cases of TMA likely associated with the use of intravitreal anti-VEGF therapy. These patients developed the signature lesion of VEGF blockade in a 6 to 11 month time frame after starting intravitreal VEGF inhibitors. The literature is reviewed showing similar cases. Intravitreal VEGF blockade may cause these adverse events in a hitherto unidentified subgroup of patients. Well-controlled prospective observational trials are needed to determine the event rate and identify which subgroups of patients are at increased risk. A registry for patients who develop worsening hypertension, proteinuria exacerbation, and glomerular diseases from intravitreal VEGF blockade is proposed.

Unbiased Analysis of Temporal Changes in Immune Serum Markers in Acute COVID-19 Infection With Emphasis on Organ Failure, Anti-Viral Treatment, and Demographic Characteristics

“…CD27 and increased expression of CXCL13 may support blast response from B cells, as is seen in COVID-19, further propelling vascular inflammation and lung injury (57). This inflammatory process is further fueled by significant activation of the VEGF activation pathways, as seen in our dataset (58). Together with CD27 and TWEAK activation, this is highly suggestive of ongoing vasculitis, a common feature of organ dysfunction in COVID-19 (51,59,60).…”

“…The only advent of kidney failure, liver failure, and need for pressors was associated with elevation of specific markers (CCL4, CD40, CXCL5, and IL-15), but our findings' interpretation needs more broad context (66). Elevation in VEGFA and CD28 in patients with kidney failure suggests its involvement in the emergence of this organ failure (58,67). Similarly to the lungs, the observed inflammatory profile suggests an environment where T cells and NK are activated.…”

Current Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features

“…A recent study reported that intravitreal injection of bevacizumab triggers TMA-like lesions in glomeruli, causing proteinuria 21,22,23 . From these findings, clinicians should be aware that even the local use of bevacizumab, such as via intravitreal injection, can lead to a systemic side effect, although the possibility is supposedly negligible.…”

Urinary biomarkers of kidney injury in patients treated with anti-VEGF drugs

“…Также вероятно постепенное снижение почечной функции вплоть до терминальной стадии [9,10]. Кроме того, возможно снижение скорости клубочковой фильтрации (СКФ) вплоть до развития острого почечного повреждения даже при интравитреальном введении [11,12]. Определение биомаркеров, которые позволили бы распознавать процессы ишемии почечного интерстиция и повреждение клубочков на ранних стадиях, может способствовать снижению риска развития почечной дисфункции при оптимизации лечения и сопутствующей терапии.…”