Nationwide Analysis of Progressive Kidney Function Decline and Diabetic Macular Edema in Type 2 Diabetes.

Purpose: To evaluate the impact of renal function on the risk of developing diabetic macular edema (DME) among patients newly diagnosed with type 2 diabetes mellitus (T2DM). Design: A retrospective cohort study. Participants: Patients with T2DM without pre-existing ophthalmic diabetic complications, stratified by kidney function (estimated glomerular filtration rate [eGFR]). Methods: We analyzed electronic health record data from the TriNetX network, including patients diagnosed with T2DM from 2005 to 2025. Patients were grouped based on baseline eGFR levels documented within 6 months of diabetes diagnosis: normal/high (≥90 mL/min), mild chronic kidney disease (CKD; 60-89 mL/min), mild-to-moderate CKD (45-59 mL/min), moderate-to-severe CKD (30-44 mL/min), severe CKD (15-29 mL/min), and end-stage renal disease (ESRD) (<15 mL/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 Diabetes Complications Severity Index components. Main Outcome Measures: Incidence of DME within 3 years after diabetes diagnosis. Results: Postmatching, each cohort was balanced in patient characteristics. Compared with patients with normal kidney function, there was a progressively higher risk of DME with declining kidney function: mild CKD (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02-1.08), mild-to-moderate CKD (HR 1.41, 95% CI 1.36-1.46), moderate-to-severe CKD (HR 1.78, 95% CI 1.70-1.87), severe CKD (HR 2.35, 95% CI 2.21-2.51), and ESRD (HR 2.53, 95% CI 2.33-2.74). Subgroup analysis restricted to normoalbuminuric patients (urine albumin-to-creatinine ratio ≤30 mg/g) also demonstrated significant associations, highlighting the potential independent effect of declining eGFR on DME risk. Additionally, kidney transplantation among ESRD patients was associated with reduced DME risk (HR 0.65, 95% CI 0.51-0.81). Conclusions: Our findings reveal a clear, progressive relationship between declining renal function and increased DME risk, independent of albuminuria. These results underscore the need for proactive ophthalmic screening in diabetic patients with impaired renal function and suggest renal improvement may mitigate DME risk. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.