Overall, intravitreal anti-VEGF injections in patients with diabetic eye disease did not seem to worsen kidney function in this study; however, an increased risk was noted in certain subgroups of patients. (This image shows a patient with DME). Photo: Jarett Mazzarella, OD. Click image to enlarge.

Anti-VEGF has become the mainstay of treatment for patients with proliferative diabetic retinopathy (PDR) and/or diabetic macular edema (DME), making it critical to continue investigating the potential adverse effects of the therapy. Recently, researchers performed a retrospective cohort study to examine whether anti-VEGF treatment influences kidney function in this patient population. While they found no increased risk of kidney function decline in most PDR and DME patients on anti-VEGF, an association did present in certain individuals including males.

The team collected data from a large tertiary care center in Chicago on 187 patients who had received at least one anti-VEGF injection (mean: 11 injections) for PDR and/or DME as well as 929 controls with nonproliferative DR who did not receive injections. The main outcome measure assessed in the injections group included time from baseline to sustained 40% decline in estimated glomerular filtration rate (eGFR).

The analysis of the data revealed no increase in the risk of kidney function decline in patients who received anti-VEGF injections (hazard ratio (HR): 1.44); however, subgroup analyses produced somewhat of a different outcome. For example, an increased risk of kidney function decline did exist in male patients on anti-VEGF, while this association was not observed in female patients. Additionally, anti-VEGF therapy appeared to increase the risk of kidney function decline in patients with baseline eGFR >30ml/min/1.73m² (HR: 1.86) but not in those with baseline eGFR ≤30ml/min/1.73m² (HR: 0.97).

“Our finding of a stronger association among those without advanced chronic kidney disease is interesting, as patients with more advanced chronic kidney disease are generally at greater risk of progression,” the researchers pointed out in their paper in Ophthalmology Science. “A potential explanation is that in the setting of more preserved eGFR, any deleterious effect of intravitreal anti-VEGF therapy may be more significant than at lower levels of kidney function, when other factors that contribute to chronic kidney disease progression may be more important.”

Interestingly, the number of injections administered didn’t seem to have any effect on the risk of kidney function decline, as the same level of risk was noted in patients receiving either less or more than 12 injections. “This may suggest an association with kidney function decline in certain predisposed individuals, regardless of the number of injections received,” the study authors explained.

They also provided their rationale behind why an association appears to exist between kidney function and anti-VEGF therapy in some individuals. “Kidney biopsies of patients treated with systemic anti-VEGF therapy demonstrated features of subacute thrombotic microangiopathy, which may suggest a potential mechanism for the pathogenesis of anti-VEGF-induced kidney injury,” they wrote in their paper. “Thus, anti-VEGF agents may impair kidney function in susceptible patients even when administered via intravitreal injection.”

Based on these findings, the team concluded that follow-up studies may be warranted to determine whether kidney function should be more closely monitored in male patients and those without advanced chronic kidney disease (eGFR >30ml/min/1.73m²) who are on anti-VEGF therapy.