Intravitreal bevacizumab-induced exacerbation of proteinuria in diabetic nephropathy, and amelioration by switching to ranibizumab

Abstract

Certain diabetic and hypertensive patients started on intravitreal vascular endothelial growth factor inhibition for diabetic retinopathy may experience worsening of hypertension and proteinuria. The etiology of this is the newly recognized absorption of intravitreally injected vascular endothelial growth factor inhibitors, and the susceptibility of patients with pre-existing renal disease to exacerbations depends on the degree of systemic absorption. There are eighteen reported cases of worsening hypertension, woresening proteinuria, worsening renal function, thrombotic microangiopathy, and glomerular disease noted after initiation of intravitreal vascular endothelial growth factor blockade. This nineteenth case demonstrates worsening hypertension and proteinuria with the start of bevacizumab. Both blood pressure and proteinuria parameters showed overall improvement with switching to the less absorbed and lower potency agent ranibizumab. There was a slight rise in serum creatinine after bevacizumab therapy, which stabilized at a new baseline, and the serum creatinine remained stable on ranibizumab. There were no other nephrotoxic exposures that explained the mild rise in serum creatinine. Because of improvement in renal function and proteinuria, a renal biopsy was deferred for the time. This case re-demonstrates the risk of worsening proteinuria with vascular endothelial growth factor inhibitors when given intravitreally in some patients. The demonstration of improvement in blood pressure and proteinuria with the use of lower potency agents like ranibizumab is novel and an important concept confirming observations from pharmacokinetic studies. The switch to ranibizumab offers a therapeutic option when proteinuria worsens with intravitreal vascular endothelial growth factor blockade, and the patient requires ongoing intravitreal therapy for treatment of diabetic retinopathy.

Refractory scleroderma renal crisis precipitated after high-dose oral corticosteroids and concurrent intravitreal injection of bevacizumab

“…There are now increasing reports of intravitreal injections resulting in VEGF depletion and glomerular disease including TMA, collapsing focal and segmental sclerosis (FSGS), as well as other causes of nephrotic syndrome. [14][15][16][25][26][27] The renal biopsy findings we presented could be compatible with TMA from VEGF depletion and from SRC. Given the presence of Ssc clinically predating the intravitreal VEGF inhibition injections, it was surmised that the patient's Ssc was likely exacerbated by VEGF blockade and hypertension as well as the oral corticosteroids.…”

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

“…Otherwise, overinhibition of VEGF-A may lead to harmful side effects. Evidenced by a recent study, receiving intravitreal bevacizumab leads to worsening proteinuria and renal function in patients with early stage of DN, but it is subsequently improved by switching to a lower potency antibody, ranibizumab ( Hanna et al, 2020 ).…”

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

“…There were previously 23 published case reports of worsening proteinuria, decreased renal function, glomerular diseases and hypertension following initiation of intravitreal VEGF blockade [ 11 , 31 , 44–54 , 56–59 ]. There are also three recently described cases of chronic thrombotic microangiopathy (TMA) associated with starting intravitreal VEGF blockade with bevacizumab and aflibercept (under review).…”