Bidirectional association of retinal vessel diameters and estimated GFR decline: The beaver dam CKD study

Background: Recent cross-sectional studies have reported an association between retinal vessel caliber and chronic kidney disease (CKD), but the direction of the association between these 2 processes is not clear. In a prospective study with multiple measurements of retinal vessel diameters and serum creatinine, we examined whether baseline retinal vessel diameter is associated with future risk of decreased kidney function, or vice versa. Study Design: Population-based cohort study. Setting & Participants: 3,199 Wisconsin adults aged 43-84 years who were followed up prospectively for 15 years. Predictor: Baseline retinal arteriolar and venular diameters for analysis 1 and baseline estimated glomerular filtration rate (eGFR) categories for analysis 2. Outcomes & Measurements: For analysis 1, incident CKD, defined as eGFR <60 mL/min/1.73 m² accompanied by a 25% decrease in eGFR, during follow-up. For analysis 2, incident retinal arteriolar narrowing, defined as a central retinal arteriolar equivalent measurement <144.0 μm, and incident retinal venular dilation, defined as a central retinal venular equivalent measurement >243.8 μm. Results: Baseline retinal arteriolar and venular diameters were not associated with 15-year risk of incident CKD. After adjustment for age, sex, diabetes, hypertension, and other confounders, the multivariable HR of incident CKD comparing the narrowest with the widest quartile was 1.15 (95% CI, 0.74-1.80) for retinal arteriolar diameter and 1.05 (95% CI, 0.67-1.67) for retinal venular diameter. Similarly, there was no significant association between eGFR and 15-year risk of incident retinal arteriolar narrowing or retinal venular widening. Compared with eGFR >90 mL/min/1.73 m² (referent), the multivariable HR for those with eGFR <45 mL/min/1.73 m² was 1.66 (95% CI, 0.93-2.96) for incident retinal arteriolar narrowing and 0.60 (95% CI, 0.17-1.85) for retinal venular widening. Limitations: Lack of data for albuminuria and loss to follow-up. Conclusions: Retinal vessel diameters and CKD may run together through shared mechanisms, but are not causally related.