SynthesisNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2023
A systematic review and meta-analysis of the effect of intravitreal VEGF inhibitors on cardiorenal outcomes.
Synthesis in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Effect of intravitreal VEGF inhibitors on renal-related adverse events in patients with diabetes mellitus: systematic review and meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Should patient enrollment criteria for anti-VEGF phase III trials be reconsidered.Journal of diabetes · 2023Trial
- Effect of intravitreal bevacizumab on kidney function and proteinuria among diabetic patients: a prospective observational study in Asian population.Renal failure · 2026Observational
- Anti-VEGF safety in evolution: A comprehensive review of ocular and systemic considerations.Indian journal of ophthalmology · 2026Review
- Intravitreal anti-VEGF therapy and risk of limb complications in individuals with diabetic eye disease.Diabetes research and clinical practice · 2025Article
- Systemic Effects of Intravitreal Anti-VEGF Therapy: A Review of Safety across Organ Systems.Ophthalmology and therapy · 2025Review
- Intravitreal vascular endothelial growth factor inhibitor systemic and renal toxicity registry.Clinical kidney journal · 2025Article
- Case report: heart failure related to intravitreal injection of anti-VEGF.BMC cardiovascular disorders · 2024Article
- Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study.Ophthalmology. Retina · 2024Observational
- GFR slope as a surrogate marker for future kidney failure.Nature reviews. Nephrology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundVascular endothelial growth factor inhibitors (VEGFis) have transformed the treatment of many retinal diseases, including diabetic maculopathy. Increasing evidence supports systemic absorption of intravitreal VEGFi and development of significant cardiorenal side effects.
methodsWe conducted a systematic review and meta-analysis (PROSPERO: CRD42020189037) of randomised controlled trials of intravitreal VEGFi treatments (bevacizumab, ranibizumab and aflibercept) for any eye disease. Outcomes of interest were cardiorenal side effects (hypertension, proteinuria, kidney function decline and heart failure). Fixed effects meta-analyses were conducted where possible.
resultsThere were 78 trials (81 comparisons; 13 175 participants) that met the criteria for inclusion: 47% were trials in diabetic eye disease. Hypertension (29 trials; 8570 participants) was equally common in VEGFi and control groups {7.3 versus 5.4%; relative risk [RR] 1.08 [95% confidence interval (CI) 0.91-1.28]}. New or worsening heart failure (10 trials; 3384 participants) had a similar incidence in VEGFi and control groups [RR 1.03 (95% CI 0.70-1.51)]. Proteinuria (5 trials; 1902 participants) was detectable in some VEGFi-treated participants (0.2%) but not controls [0.0%; RR 4.43 (95% CI 0.49-40.0)]. Kidney function decline (9 trials; 3471 participants) was similar in VEGFi and control groups. In participants with diabetic eye disease, the risk of all-cause mortality was higher in VEGFi-treated participants [RR 1.62 (95% CI 1.04-2.46)].
conclusionIn trials of intravitreal VEGFi, we did not identify an increased risk of cardiorenal outcomes, although these outcomes were reported in only a minority of cases. There was an increased risk of death in VEGFi-treated participants with diabetic eye disease. Additional scrutiny of post-licensing observational data may improve the recognition of safety concerns in VEGFi-treated patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.