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

Abstract

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.

In Vivo Assessment of Individual and Total Proteinuria in Zebrafish Larvae Using the Solvatochromic Compound ZMB741

“…8 Molecular weight distributions can also be used to monitor the progression of kidney disease and to assess the response to treatment. 4,5 The zebrafish pronephros, with its simple and functional segmentation, is a favorable model to study mammalian nephrons, as they share several similarities. 9,10,11,12 Based on the mapping of expressed genes, it has been observed that the pronephric duct, previously thought to be a uniform duct, is actually composed of multiple segments, including the proximal convoluted tubule, proximal straight tubule, distal early tubule, corpuscle of Stannius, and distal late tubule.…”

“…Molecular weight distributions of urinary proteins aid in diagnosing different types of kidney disease, including diabetic nephropathy, chronic kidney disease, and glomerulonephritis . Molecular weight distributions can also be used to monitor the progression of kidney disease and to assess the response to treatment. , …”

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

“…Following publication of the original article [ 1 ], the authors have replaced the Supplementary Information (Additional file 1 ).…”