Table 3:
Positive studies showing effect between IVEGFi and renal function.
| (A) Pharmacological studies | ||
| Absorption in AMD, dec. systemic VEGF (Bev, Aflb) > Ran | Prospective observational study | Avery |
| Absorption in AMD/DME/CRVO, dec. systemic VEGF (Bev, Aflib)>Ran | Prospective observational study | Avery |
| Dec. systemic VEGF (Bev, Aflib) > Ran | Prospective randomized clinical study | Jampol |
| Absorption of drug in AMD, dec. systemic VEGF | Retrospective study of RCT data | Rogers |
| Dec. systemic VEGF (Bev, Aflib) | Prospective randomized observational study | Zehetner |
| Bev > Ran dec. in systemic VEGF | Prospective observational study | Yoon |
| Dec. systemic VEGF (Bev, Aflib) | Prospective non randomized clinical study | Hirano |
| (B) Animal studies/biomarker studies | ||
| Absorption of drug, binding at glomerulus | Animal (simian) study | Tschulakow |
| NGAL, KIM-1, HIF-1alpha, Nephrin levels increase post VEGFi (intravitreal injection) suggesting renal tissue injury | Basic science study | Chebotareva |
| (C) Clinical studies showing changes in blood pressure | ||
| Higher blood pressure linked to need for more VEGFi | Retrospective study | Shah |
| Limited short-term rise in blood pressure at 1 h | Prospective observational study | Lee |
| Long- and short-term rise in systolic blood pressure | Observational study | Rasier |
| (D) Clinical studies showing changes in proteinuria | ||
| Increased proteinuria 45% of patients (not statistically significant) | Prospective observational study | Bagheri |
| Significant rise in diastolic blood pressure | ||
| Significant rise in hemoglobin and platelets | ||
| 4% of patients with AKI and elevated UPCR after VEGFi | Retrospective observational study | Jalalonmuhali |
| Significant rise in UPCR in patients with preexisting proteinuria | Prospective observational study | Chung |
| (E) Studies showing changes in renal function | ||
| Increase risk of AKI in male patients and those with eGFR >30 mL/min | Retrospective cohort study | Bunge |
| Increase in MACR and drop in eGFR post-intravitreal injection | Retrospective cohort study | Del Cura Mar |
| Injected cohort with greater drop in eGFR than controls | Retrospective cohort study | Ou |
| Injected cohort of diabetic patients demonstrates greater drop in eGFR than in controls | Retrospective observational cohort study | Rivero |
| 85%–120% relative risk increase of dialysis need in VEGFi (intravitreal) treated individuals | Retrospective cohort study using national database | Yang |
| 33% increase risk of CKD progression in patients treated with VEGFi (intravitreal) compared with laser photocoagulation | Retrospective cohort study | Chen |
| 18 cases showing worsening HTN, eGFR and UPCR/MACR | Registry of clinical events | Hanna et al. (unpublished) |
| Elevated risk but similar risk of renal injury amongst VEGF inhibitors (Bev = Ran = Aflib = Faric) | Meta-analysis | Cai |
| (F) Epidemiological studies showing increase in population adverse events | ||
| Increased risk of CVA in DME patients | Meta-analysis | Avery |
| Increased all-cause mortality in AMD patients | Retrospective observational study | Hanhart |
| Increased risk of mortality after MI in AMD patients | Retrospective observational study | Hanhart |
| Increased risk of mortality after CVA in AMD patients | Retrospective observational study | Hanhart |
| Increased risk of thrombotic events | Clinical trial database retrospective | Schmid |
| Increased risk of death in DM patients treated with VEGF blockade | Meta-analysis | Lees |
Aflib, aflibercept; Bev, bevacizumab; CRVO, central retinal vein obstruction; dec., decreased; Faric, faricimab; HIF 1alpha, hypoxia inducing factor 1 alpha; KIM-1, kidney injury molecule-1; MACR, microalbumin to creatinine ratio; n, number of study subjects; NGAL, neutrophil gelatinase associated lipocalin; Ran, ranibizumab; RCT, randomized controlled trial; SAE, serious adverse event.