Investigation of associations between retinal microvascular parameters and albuminuria in UK Biobank: a cross-sectional case-control study

Abstract

Background: Associations between microvascular variation and chronic kidney disease (CKD) have been reported previously. Non-invasive retinal fundus imaging enables evaluation of the microvascular network and may offer insight to systemic risk associated with CKD.

Methods: Retinal microvascular parameters (fractal dimension [FD] - a measure of the complexity of the vascular network, tortuosity, and retinal arteriolar and venular calibre) were quantified from macula-centred fundus images using the Vessel Assessment and Measurement Platform for Images of the REtina (VAMPIRE) version 3.1 (VAMPIRE group, Universities of Dundee and Edinburgh, Scotland) and assessed for associations with renal damage in a case-control study nested within the multi-centre UK Biobank cohort study. Participants were designated cases or controls based on urinary albumin to creatinine ratio (ACR) thresholds. Participants with ACR ≥ 3 mg/mmol (ACR stages A2-A3) were characterised as cases, and those with an ACR < 3 mg/mmol (ACR stage A1) were categorised as controls. Participants were matched on age, sex and ethnic background.

Results: Lower FD (less extensive microvascular branching) was associated with a small increase in odds of albuminuria independent of blood pressure, diabetes and other potential confounding variables (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03-1.34 for arterioles and OR 1.24, CI 1.05-1.47 for venules). Measures of tortuosity or retinal arteriolar and venular calibre were not significantly associated with ACR.

Conclusions: This study supports previously reported associations between retinal microvascular FD and other metabolic disturbances affecting the systemic vasculature. The association between retinal microvascular FD and albuminuria, independent of diabetes and blood pressure, may represent a useful indicator of systemic vascular damage associated with albuminuria.

Fig. 1

Study cohort eligibility selection criteria

Fig. 2

Associations between retinal microvascular parameters and measures of renal function and damage. Associations between retinal microvascular parameters (Z scores) and a: ACR > 3 mg/mmol; b: eGFR < 60 ml/min/1.73m² (combined CKD-EPI for both serum creatinine and serum cystatin C); c: ACR > 3 mg/mmol and/or eGFR < 60 ml/min/1.73m² combined CKD-EPI for both serum creatinine and serum cystatin C), for Model 2 (adjusted for age, sex, waist circumference, systolic blood pressure, blood pressure-lowering medication usage, presence of diabetes mellitus, smoking history (as a binary variable, ever smoked versus never smoked), ethnicity (as a binary variable, white ethnicity versus non-white ethnicity), and alcohol consumption (ever versus never)).*Association significant at the p < 0.05 level. ACR: albumin to creatinine ratio; CRAE: central retina arteriolar equivalent; CRVE: central retinal venular equivalent; AVR: arteriovenous ratio; FDa/v: arteriolar/venular fractal dimension; Torta/v: arteriolar/venular tortuosity. Bars indicate 95% confidence intervals