Nephrotic Syndrome with Focal Segmental Glomerulosclerosis Induced by Intravitreal Injections of Vascular Endothelial Growth Factor Inhibitor

Kakeshita, Kota; Koike, Tomoyuki; Imamura, Teruhiko; Murai, Sayaka; Fujioka, Hayato; Yamazaki, Hidenori; Kinugawa, Koichiro

doi:10.2169/internalmedicine.5410-20

Cited by 3 publications

(3 citation statements)

References 9 publications

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“…Previous studies have suggested that systemic anti-VEGF therapy is associated with renal function impairment [12,13]. However, other studies have disputed the relationship between nephrotoxicity and intravitreal VEGF inhibitors [5,6,[14][15][16]. There are a number of population studies showing that intravitreal anti-VEGF agents are associated with nephrotoxicity and with increased mortality [5].…”

Section: Discussionmentioning

confidence: 99%

“…Nobakht et al reported one case of kidney function gradually declining after 148 administrations of intravitreal ranibizumab, bevacizumab, and aflibercept injections, eventually resulting in a need for hemodialysis [15]. Kakeshita et al reported one case of renal focal segmental glomerulosclerosis after intravitreal aflibercept [16].…”

Section: Discussionmentioning

confidence: 99%

“…It is suggested that diabetic patients can receive IVI VEGF inhibitors safely without significant renal function decline. Nevertheless, since previous studies reported adverse effects on renal function after therapy of IVI VEGF inhibitors [5,6,[14][15][16], it is reasonable to monitor renal function in patients receiving IVI anti-VEGF therapy regularly. Further prospective studies are required to confirm our results and elucidate the systemic effects of IVI anti-VEGF therapy.…”

Section: Discussionmentioning

confidence: 99%

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Changes of Estimated Glomerular Filtration Rate and Glycated Hemoglobin A1c in Diabetic Macular Edema Patients Treated by Ranibizumab and Aflibercept in the Tertiary Referral Hospital

Tien

Lin

et al. 2022

Medicina

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Background and Objectives: Intravitreal injections (IVI) of vascular endothelial growth factor (VEGF) inhibitors are guideline-indicated treatments for diabetic macular edema (DME). However, some recent data have suggested that IVI VEGF inhibitors might, through systemic absorption, lead to a reduction in renal function. Our study aims to compare changes in glycated hemoglobin A1c (HbA1c) and estimated glomerular filtration rate (eGFR) between patients who received IVI ranibizumab and aflibercept treatment and patients who have not received IVI treatments. Materials and Methods: There were 17,165 DME patients with documented ophthalmology visits in the China Medical University Hospital-Clinical Research Data Repository. Those with a history of ESRD or bevacizumab treatment history, and those with missing information on HbA1c or eGFR, were excluded. After matching by age (±2 years), gender, and the year of clinical visit, 154 patients with medical treatment (including ranibizumab and aflibercept) and 154 patients without medical treatment were included in the study. The difference between HbA1c and eGFR at baseline and 3 and 12 months after the index date between the two groups was assessed. Results: Mean HbA1c and eGFR decreased between baseline and 12 months after the index date in both groups (p < 0.05). Compared with the non-treatment group, the treatment group had significantly lower HbA1c 3 and 12 months after the index date. There was no significant difference in eGFR between the two groups. In the generalized estimating equations (GEE) model, HbA1c in the treatment group was lower than the non-treatment group (−0.44%, 95% CI = −0.75, −0.14), but eGFR was similar after adjusting for age, gender, and index-year. HbA1c and eGFR decreased with the time in the adjusted GEE model (p < 0.0001) in both groups. Conclusions: This study showed that eGFR decreased with age and time and was not related to IVI anti-VEGF treatments in our tertiary referral hospital. IVI anti-VEGF therapy was also associated with better HbA1c control. It is suggested that DME patients can receive intravitreal VEGF inhibitors without inducing more renal impairment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Changes of Estimated Glomerular Filtration Rate and Glycated Hemoglobin A1c in Diabetic Macular Edema Patients Treated by Ranibizumab and Aflibercept in the Tertiary Referral Hospital

Tien

Lin

et al. 2022

Medicina

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Aflibercept/amlodipine/irbesartan

2021

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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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Nephrotic Syndrome with Focal Segmental Glomerulosclerosis Induced by Intravitreal Injections of Vascular Endothelial Growth Factor Inhibitor

Cited by 3 publications

References 9 publications

Changes of Estimated Glomerular Filtration Rate and Glycated Hemoglobin A1c in Diabetic Macular Edema Patients Treated by Ranibizumab and Aflibercept in the Tertiary Referral Hospital

Changes of Estimated Glomerular Filtration Rate and Glycated Hemoglobin A1c in Diabetic Macular Edema Patients Treated by Ranibizumab and Aflibercept in the Tertiary Referral Hospital

Aflibercept/amlodipine/irbesartan

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

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