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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.

SUBMITTER: Hanna RM

PROVIDER: S-EPMC7026818 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Hanna Ramy M RM Abdelnour Lama L Hasnain Huma H Selamet Umut U Kurtz Ira I

SAGE open medical case reports 20200216

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 worseni ...[more]

PMID: 32110410

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Project description:BackgroundThe relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown.MethodsAt 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year.ResultsFrom baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P=0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P=0.003 for aflibercept vs. ranibizumab, and P=0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P=0.40), hospitalization (P=0.51), death (P=0.72), or major cardiovascular events (P=0.56).ConclusionsIntravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249.).

Dataset Information

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

Publications

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

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