Chronic Kidney Disease Severity and Progression to Proliferative Diabetic Retinopathy

AIMS: To determine whether chronic kidney disease (CKD) severity is associated with progression from nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) and severe retinal complications. MATERIALS AND METHODS: In this retrospective TriNetX cohort study, adults with Type 2 diabetes and NPDR were matched 1:1 by CKD stage (1-2, 3, 4-5 or end-stage renal disease [ESRD]) to patients without CKD. Patients with prior PDR, diabetic macular oedema, intravitreal treatment, or vitrectomy were excluded. Cox models estimated 3-year hazard ratios (HRs) for PDR and a composite of PDR, vitreous haemorrhage, tractional retinal detachment or vitrectomy. Sensitivity analyses used laboratory-defined estimated glomerular filtration rate and cohorts restricted to mild NPDR or documented baseline haemoglobin A1c. RESULTS: Matched comparisons included 8476, 24 432, 9933 and 7359 patients with CKD Stages 1-2, 3, 4-5 and ESRD, respectively, with equal-sized reference cohorts. PDR risk increased with CKD severity: HR 1.12 (95% confidence interval [CI] 0.96-1.29) for Stages 1-2, 1.35 (1.23-1.47) for Stage 3, 1.59 (1.40-1.80) for Stages 4-5 and 1.66 (1.45-1.89) for ESRD. Similar associations were observed for the composite and persisted in laboratory-defined and mild-NPDR-restricted analyses, although residual baseline haemoglobin A1c imbalance remained in advanced CKD comparisons. CONCLUSIONS: CKD Stage 3 or higher was associated with greater progression from NPDR to PDR and severe retinal complications. CKD severity may identify higher-risk patients, although prospective studies are needed before CKD-specific surveillance is recommended.