Renal function after intravitreal administration of vascular endothelial growth factor inhibitors in patients with diabetes and chronic kidney disease

Kameda, Yutaka; Babazono, Tetsuya; Uchigata, Yasuko; Kitano, Shigehiko

doi:10.1111/jdi.12771

Cited by 33 publications

(36 citation statements)

References 14 publications

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“…In another study, diabetic patients accepted intravitreal anti-VEGF agents rapidly developed worsening proteinuria and renal function decline ( Hanna et al, 2019 ). On the contrary, a current study showed that the average eGFR did not change in a total of 69 diabetic patients who received intravitreal anti-VEGF agents ( Kameda et al, 2018 ). In addition, no episode of acute kidney injury occurred.…”

Section: The Role Of Vegf-a In Abnormal Angiogenesis Of Dncontrasting

confidence: 56%

“…The VEGF-A inhibitors have previously shown some beneficial effects on diabetic ocular disease and DN experimental mice models, but recent evidences raised controversial opinions on its use in clinical practice. Several lines of evidence revealed that patients accepted anti-VEGF treatment developed worsening proteinuria and glomerular microangiopathy ( Hanna et al, 2019 ; Touzani et al, 2019 ), while other studies supported that it is unlikely to cause any renal injury ( Kameda et al, 2018 ; O’Neill et al, 2019 ). Leucine-richα-2-glycoprotein 1 (LRG1) is a novel pro-angiogenic factor that has demonstrated to promote angiogenesis by enhancing ALK-1signaling pathway in both diabetic ocular disease and DN mouse models ( Wang et al, 2013 ; Haku et al, 2018 ; Hong et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Diabetic nephropathy (DN) is an important public health concern of increasing proportions and the leading cause of end-stage renal disease (ESRD) in diabetic patients. It is one of the most common long-term microvascular complications of diabetes mellitus that is characterized by proteinuria and glomerular structural changes. Angiogenesis has long been considered to contribute to the pathogenesis of DN, whereas the molecular mechanisms of which are barely known. Angiogenic factors associated with angiogenesis are the major candidates to explain the microvascular and pathologic finds of DN. Vascular endothelial growth factor A (VEGF-A), leucine-rich α-2-glycoprotein 1, angiopoietins and vasohibin family signal between the podocytes, endothelium, and mesangium have important roles in the maintenance of renal functions. An appropriate amount of VEGF-A is beneficial to maintaining glomerular structure, while excessive VEGF-A can lead to abnormal angiogenesis. LRG1 is a novel pro-angiogenic factors involved in the abnormal angiogenesis and renal fibrosis in DN. The imbalance of Ang1/Ang2 ratio has a role in leading to glomerular disease. Vasohibin-2 is recently shown to be in diabetes-induced glomerular alterations. This review will focus on current understanding of these angiogenic factors in angiogenesis and pathogenesis associated with the development of DN, with the aim of evaluating the potential of anti-angiogenesis therapy in patients with DN.

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Section: The Role Of Vegf-a In Abnormal Angiogenesis Of Dncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…A retrospective study of renal safety following acute anti-VEGF exposure showed no significant change in mean eGFR and no episodes of acute kidney injury, following a single intravitreal anti-VEGF injection of ranibizumab, aflibercept or bevacizumab, in a cohort of 69 patients with DM and CKD [29]. However, the study by Kameda and colleagues did not consider the potential cumulative effects of intravitreal anti-VEGF exposure on renal function.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of long-term intravitreal anti-vascular endothelial growth factor injections on renal function in patients with and without diabetic kidney disease

et al. 2019

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BackgroundAdministering anti-vascular endothelial growth factor (anti-VEGF) by intraocular injection has been shown to have a safe systemic profile. Nevertheless, incidents of acute kidney injury following anti-VEGF injection have been reported. We assessed the long-term effect of multiple intravitreal anti-VEGF injections on measures of renal function in patients with diabetes including rate of change of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR).MethodsA retrospective review of patients receiving diabetic macular oedema (DMO) treatment was undertaken. Serum creatinine, ACR, number of intravitreal anti-VEGF injections and clinical characteristics were collected from electronic healthcare records (EHR). A co-efficient of eGFR and ACR change with time was calculated over a mean duration of 2.6 years. Regression modelling was used to assess variation in the number of anti-VEGF injections and change in eGFR and ACR.ResultsThe EHR of 85 patients with DMO (59% male, 78% type 2 diabetes mellitus [T2DM]) were reviewed. On average, 26.8 intravitreal anti-VEGF injections were given per patient over a mean duration of 31 months. No association between increasing number of anti-VEGF injections and rate of eGFR decline (beta = 0.04, 95% confidence intervals [CI]: − 0.02, 0.09; p = 0.22) or ACR change over time (beta = 0.02, CI: − 0.19, 0.23; p = 0.86) was detected, following adjustment for hypertension, cerebrovascular disease, T2DM, and medications taken.ConclusionOur data suggests regular long-term intravitreal VEGF inhibition does not significantly alter the rate of change in eGFR and/or ACR with increasing number of treatment injections.

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“…70 A recent retrospective study of 69 patients did not report acute kidney injury after a short-term follow-up of 7 to 30 days after intravitreal injections of bevacizumab, aflibercept, or ranibizumab. 71 Levels of anti-VEGF agents and proteinuria were not monitored. This Japanese study also raised the possibility that differences in genetic background might modulate differences in renal toxicity among patients.…”

Section: Intravitreal Anti-vegf Administration: Systemic Absorptionmentioning

confidence: 99%

Nephrotoxicity induced by intravitreal vascular endothelial growth factor inhibitors: emerging evidence

Hanna

Barsoum

Arman

et al. 2019

Kidney International

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Renal function after intravitreal administration of vascular endothelial growth factor inhibitors in patients with diabetes and chronic kidney disease

Cited by 33 publications

References 14 publications

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

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

Evaluation of long-term intravitreal anti-vascular endothelial growth factor injections on renal function in patients with and without diabetic kidney disease

Nephrotoxicity induced by intravitreal vascular endothelial growth factor inhibitors: emerging evidence

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