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.

Systemic retinal biomarkers

“…Paterson et al . [22] found an independent association between albuminuria and retinal microvascular fractal dimension in fundus photographs. Tom et al .…”

“…O'Neill et al [20] found an association between retinal vascular tortuosity and chronic kidney disease (CKD) stages 3-5, while the metaanalysis by Lye et al [21] found no significant association between retinal vascular calibre and CKD, all in fundus photographs. Paterson et al [22] found an independent association between albuminuria and retinal microvascular fractal dimension in fundus photographs. Tom et al [23] and Wang et al [24] found that retinal perfusion and vessel density on OCT-A correlated with CKD in diabetic patients, while Wu et al identified a similar relationship in CKD patients [25].…”

Association of retinal fractal dimension and vessel tortuosity with impaired renal function among healthy Chinese adults

“…There have been studies exploring the association between retinal FD and renal function based on digital fundus imaging or fundus fluorescein angiography. Some studies indicated a positive association of FD with CKD and GFR (11,28,29), while others showed no Scattergram showing linear correlation between fractal dimension in the superficial capillary plexus and estimated glomerular filtration rate.…”

An Overview of Vascular Dysfunction and Determinants: The Case of Children of African Ancestry

“…Endothelial function is mostly assessed by flow mediated dilation (FMD) techniques, which require occlusion. Retinal imaging is mostly used to assess the functioning microcirculation, and the macrocirculation function can be assessed by measuring the pulse wave velocity (PWV) as discussed below (67,68).…”