Effects of intravitreal anti-VEGF injections on renal function over the long term

Daniel Choi, MD, and colleagues from the University of Pennsylvania, Philadelphia, investigated the effect of anti-vascular endothelial growth factor (VEGF) therapies in patients over the long term and overall found no association between the treatments and the risk of chronic kidney disease or end-stage renal disease.

They commented that while intravitreal anti-VEGF can reduce plasma-free-VEGF, the literature contains little information on the safety of long-term intravitreal anti-VEGF injections on the body and especially the kidney.

In this study, the investigators used a commercial and Medicare Advantage medical claims database to identify patients who had been treated with an intravitreal anti-VEGF agent and the numbers of injections administered over 4 years after the initial injection. The patients who met the inclusion criteria were divided into quartiles based on the number of injections they received and the highest and lowest quartiles were compared.

The authors also looked at individual diseases, i.e., neovascular age-related macular degeneration (AMD), macular edema associated with retinal vein occlusion (RVO), and diabetic retinopathy (DR). They also used Cox proportional regression analysis to assess an every-5-injection increase in the hazard of developing kidney disease, they described.

Results of analysis

The results showed that 13,895 patients had received 1 to 3 anti-VEGF injections (lowest quartile) and 13,881 had received more than 21 or more injections (highest quartile).

In the lowest and highest quartiles, respectively, the patients with neovascular AMD received 6,228 injections (1 to 4 injections) and 6,172 had 24 or more injections (24 or more injections); those with macular edema due to RVO, 573 (1 to 2 injections) and 580 (12 or more injections); and those with DR, 523 (1 to 2 injections) and 517 (13 or more injections).

The authors reported that for patients in the highest quartile, the weighted analysis showed no association overall with development of kidney disease (odds ratio [OR], 1.00, 95% confidence interval [CI], 0.98-1.01, p=0.58) or in patients with neovascular AMD (OR, 0.99, 95% CI, 0.97-1.02, p=0.48), decreased odds in macular edema due to RVO (OR, 0.93, 95% CI, 0.86-0.99, p=0.04), and increased odds in DR (OR, 1.12, 95% CI, 1.03-1.22, p=0.01). Cox analysis showed no association overall or for any subgroup (hazard ratio, 0.97-1.01, p>0.27 for all comparisons).

The authors concluded, “While logistic regression showed some association of the increased number of injections with kidney disease, the Cox analysis did not confirm these findings, suggesting time was a confounder in the logistic regression analysis.”