Reduced Renal Function a Risk Factor for DME

Authors of this study suggest the need for proactive ophthalmologic screening in diabetic patients with impaired renal function, potentially more frequently than the usual annual exam for those with moderate-to-severe CKD—such as every six to 12 months. They also suggest aggressive management of systemic risk factors and interventions to slow CKD progression that may mitigate DME risk. Photo: Carolyn Majcher, OD. Click image to enlarge. Many components of systemic health are intimately involved in the development of retinal pathology, including chronic medication use and overall organ health. In a recent study, researchers evaluated the impact of renal function on the risk of developing diabetic macular edema (DME) among patients newly diagnosed with type 2 diabetes and found a clear, progressive relationship between declining renal function and increased DME risk, even in the presence of normoalbuminuria. The findings were reported in Ophthalmology Science.Data from the TriNetX network of patients diagnosed with diabetes from 2005 to 2025 were analyzed. These patients had no pre-existing ophthalmic diabetic complications and were stratified by kidney function as measured by estimated glomerular filtration rate (eGFR). They were grouped based on baseline eGFR levels documented within six months of being diagnosed with diabetes as follows: normal/high (≥90mL/min)mild chronic kidney disease (CKD; 60-89mL/min)mild-to-moderate CKD (45-59mL/min)moderate-to-severe CKD (30-44mL/min)severe CKD (15-29mL/min)endstage renal disease (<15mL/min) Propensity score matching balanced covariates including age, sex, race/ethnicity, hemoglobin A1c, hypertension, hyperlipidemia, insulin and oral hypoglycemic agent use, fenofibrate use, prostaglandin analog use and various diabetes complications. There was a progressively higher risk of DME as kidney function declined. Compared to patients with normal kidney function, the risk of DME increased from HR of 1.05 in mild CKD to 2.53 in endstage renal disease. This relationship was also observed in a subgroup of patients with normoalbuminuria (normal urine albumin levels), suggesting that reduced renal function is an independent risk factor for DME.This association likely reflects the shared pathophysiological mechanisms central to diabetic microvascular complications. “Interactions among immune cells, endothelial cells and retinal parenchyma elevate proinflammatory mediators” such as inflammatory cytokines, interleukin-6, lipids and VEGF “that contribute directly to retinal vascular injury and permeability,” the researchers explained in their paper. These alterations induce chronic vascular stress, damage and endothelial dysfunction, closely mirroring pathological processes observed in retinal vessels during DME progression.Additionally, impaired glucose tolerance and insulin resistance—central metabolic disturbances in diabetes—further perpetuate systemic inflammation, oxidative stress and vascular damage, creating an environment conducive to simultaneous renal and retinal microvascular injury, the authors continued. Impaired renal function may result in increased body fluid volumes, which has been linked to DME.“Collectively, these interconnected pathways emphasize that CKD severity not only marks advanced or poorly controlled diabetes but actively contributes to DME pathogenesis,” the authors wrote in their paper. “Therefore, therapeutic strategies targeting these common inflammatory, metabolic and hemodynamic mechanisms may effectively mitigate both renal and retinal diabetic complications.” A subgroup analysis was performed to patients with documented normoalbuminuria and eGFR measurements, and the relationship between declining renal function and increased DME risk remained significant, although the overall risks were lower compared to the primary analysis.“In normoalbuminuric patients with type 2 diabetes, renal impairment can occur independently of albuminuria due to underlying glomerular hyperfiltration and structural renal changes, such as increased glomerular filtration surface area, which gradually reduce eGFR,” the authors explained in their paper. “Furthermore, damage to endothelial cells promotes increased vascular permeability, inflammation and compromised microvascular integrity, connecting the pathological pathways of renal and retinal diseases independently of albuminuria status.”Kidney transplants in endstage disease patients were associated with a reduced risk of DME, suggesting that improved renal function post-transplantation may lessen systemic microvascular complications, reducing the risk of retinal pathology.Diabetic patients with moderate-to-severe CKD are a high-risk group for DME and may benefit from more frequent retinal screening exams, such as every six to 12 months for earlier DME detection, the researchers concluded. “Moreover, aggressive management of systemic risk factors and interventions to slow CKD progression (e.g., optimal glycemic and blood pressure control and use of SGLT2 inhibitors or RAAS blockade) should be emphasized, as these may reduce DME incidence and potentially the need for intravitreal anti-VEGF injections,” they wrote.Click here for the journal source. Muayad J, Tukur HN, Loya A, et al. Nationwide analysis of progressive kidney function decline and diabetic macular edema in type 2 diabetes. Ophthalmol Sci. September 23, 2025. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.