Effect of a Single Intravitreal Bevacizumab Injection on Proteinuria in Patients With Diabetes

Younghae, Chung; Kim, Young Ho; Byeon, Hye Eun; Jo, Dong Hyun; Kim, Jeong Hun; Lee, Kihwang

doi:10.1167/tvst.9.4.4

Cited by 11 publications

(12 citation statements)

References 44 publications

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“…This is similar to preeclampsia, a naturally occurring disease model that approximates the pharmacologic phenomenon of VEGF blockade (49). This model of differential susceptibility to VEGF depletion has been suggested by a recently conducted South Korean study, showing that patients with more proteinuria at baseline were more likely to experience worsening proteinuria after intravitreal VEGF injections (47).…”

Section: Discussionsupporting

confidence: 52%

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

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 52%

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

et al. 2020

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“…Despite limited data, risks of intravitreal VEGF inhibition can be approximated to be near 14% for hypertension worsening and 14–45% for proteinuria worsening [ 31 , 33 , 37 ]. The risks are lower than systemic VEGF inhibition administration, where 23.6% of patients have worsening hypertension and 21–63% have worsening proteinuria [ 62 , 63 , 64 ].…”

Section: New Developments In the Investigation Of The Systemic Effectmentioning

confidence: 99%

Worsening proteinuria and renal function after intravitreal vascular endothelial growth factor blockade for diabetic proliferative retinopathy

Shye

Hanna

Patel

et al. 2020

Clinical Kidney Journal

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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.

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“…In animal studies, VEGFI binding was detected in the glomeruli of monkeys after intravitreal injection of VEGFI [ 5 ]. Although experimental studies did not demonstrate a significant association between intravitreal injection of VEGFIs and renal dysfunction or proteinuria [ 6 – 9 ], some clinical studies suggesting an association between VEGFIs and renal dysfunction or proteinuria are beginning to appear [ 10 , 11 ]. Hypertension has not been clearly demonstrated as a side effect of intravitreal injection of VEGFIs; however, there has been a recent increase in positive clinical studies reporting a relationship between them [ 6 , 7 , 12 – 15 ].…”

Section: Discussionmentioning

confidence: 99%

Renal thrombotic microangiopathy and nephrotic proteinuria induced by intravitreal injection of aflibercept for diabetic macular edema

et al. 2022

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Background 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. Case presentation 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. Conclusions 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.

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Effect of a Single Intravitreal Bevacizumab Injection on Proteinuria in Patients With Diabetes

Cited by 11 publications

References 44 publications

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

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

Worsening proteinuria and renal function after intravitreal vascular endothelial growth factor blockade for diabetic proliferative retinopathy

Renal thrombotic microangiopathy and nephrotic proteinuria induced by intravitreal injection of aflibercept for diabetic macular edema

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