Comparison of Renal Adverse Events Between Intravitreal Anti–Vascular Endothelial Growth Factor Agents: A Meta-Analysis
Bibliographic record
Abstract
PURPOSE: To compare the risk of renal adverse events, particularly acute kidney injury (AKI), between intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents. DESIGN: Meta-analysis. METHODS: A systematic literature search was conducted on Ovid Medline, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published from January 2005 to February 2024 involving adult patients receiving anti-VEGF intravitreal injections for age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion. The primary outcome was the comparative risk of AKI between anti-VEGF agents and sham injections. Secondary outcomes involved other renal adverse events. Subgroup analyses were conducted by specific disease indications. A random-effects model was used for meta-analysis to estimate risk ratios (RRs) and their 95% confidence intervals, with a P value of <.05 representing statistical significance. Risk of bias was assessed using the Cochrane Risk of Bias 2 (ROB2) tool, and the certainty of evidence was evaluated through the Cochrane Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. RESULTS: A total of 10,031 eyes from 11 RCTs were included. No significant differences were found in the risk of acute or chronic renal conditions, obstructive uropathies, neoplasia, or infectious processes between anti-VEGF agents and sham therapy. AKI was reported in 5.4% (n = 10/185) of patients treated with bevacizumab, 1.3% (n = 6/456) with sham, 1.0% (n = 48/4724) with aflibercept, 0.8% (n = 15/1929) with faricimab, 0.5% (n = 5/1098) with brolucizumab, and 0.3% (n = 5/1639) with ranibizumab. No significant differences in AKI risk were observed between any of the anti-VEGF agents and sham (P > .05 for all comparisons). However, there was an increased risk of patient-reported symptoms with 1.25 mg bevacizumab compared to 2 mg aflibercept (RR = 3.26, 95% CI = 1.07-9.93, P = .04), driven primarily by reports of hematuria: 4.3% (bevacizumab), 0.7% (sham), 0.2% (aflibercept), 0.1% (faricimab), and 0.1% (ranibizumab). CONCLUSIONS: US Food and Drug Administration (FDA)-approved intravitreal anti-VEGF agents do not significantly increase the risk of AKI compared to sham injections. Nevertheless, variations in patient-reported renal symptoms were observed across different anti-VEGF drugs. These variations were influenced primarily by differences in hematuria events, which may be a result of differential systemic absorption by these agents. These results underscore the importance of continuous monitoring and pharmacovigilance.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.008 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.012 | 0.026 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".