Retinal vascular parameters, retinopathy tied to incident CKD risk
Small retinal arterioles, larger retinal venules and retinopathy are all associated with higher chronic kidney disease (CKD) risk, especially in individuals with diabetes, a new population-based study from Singapore has shown.
“Our findings suggest that retinal microvascular abnormalities may reflect early subclinical damage in the renal microvasculature that is subsequently associated with development of CKD,” researchers said.
Data of 1,256 adults were retrieved from the Singapore Malay Eye Study. Exclusion criteria were missing information on estimated glomerular filtration rate (eGFR) and covariates, ungradable baseline retinal photographs, history of cardiovascular disease and prevalent CKD.
Cox proportional hazards regression was used to determine the relationship between various retinal parameters such as central retinal artery equivalent (CRAE), CR vein equivalent (CRVE), retinal tortuosity and vascular fractal dimension (Df), retinopathy and retinal branching angle, with the study outcome of incident CKD.
Over a median follow-up of 6 years, there were 78 reported cases of CKD, most of which (94.9 percent; n=74) were from participants with hypertension and 70.5 percent (n=55) were from participants with diabetes. [Sci Rep 2017;7:9374]
In the multivariable model, every standard deviation (SD) decrease in CRAE was significantly associated with higher risks of CKD (hazard ratio [HR], 1.34; 1.00 to 1.78; p=0.048). On the other hand, tertile analysis showed that CRAE was not significantly associated with incident CKD.
In contrast, tertile analysis showed that the risk for incident CKD was significantly higher in the highest CRVE tertile (HR, 2.35; 1.12 to 5.94; p=0.025), while a per-SD increase in CRVE was not significantly associated with CKD risk (HR, 1.25; 0.95 to 1.654; p=0.116).
The presence of retinopathy was also significantly correlated with incident CKD according to multivariable analysis (HR, 2.54; 1.48 to 4.36; p=0.001).
These trends remained strong in diabetic patients. Prior to adjustments for confounders, smaller CRAE (HR per SD increase, 1.49; 1.00 to 2.21), wider CRVE (HR per SD increase, 1.47; 1.03 to 2.11) and retinopathy (HR, 2.35; 1.30 to 4.23) were all associated with CKD.
After adjustments, only retinopathy remained associated with CKD (HR, 3.78; 1.72 to 8.32).
Arteriolar and venular tortuosity, arteriolar and venular branching angles, and Df were all not associated with CKD.
“Retinal arteriolar narrowing has been hypothesized to represent a dysregulation of the renin-angiotensin and endothelin,” said researchers. [J Am Soc Nephrol 1996;7:667-675; J Am Soc Nephrol 2000;11:1702-1711]
Additionally, experimental evidence from type 1 diabetes patients had shown that narrower retinal arteries were associated with accumulation of extracellular matrix, which could result in declining eGFR. [Diabetologia 2010;53:1638-1646]
“Together, it is plausible that these processes may provide a common pathophysiologic link between retinal arteriolar narrowing and decrease in eGFR,” researchers added.
The link between venular widening and CKD are less clear. Retinal venular widening because of increased blood flow has been linked to diabetes, both of which contribute to endothelial damage. While not certain, this may suggest that retinal venular widening is a manifestation of microvascular damage in the kidney which may eventually lead to CKD, according to researchers. [Diabetologia 2015;58:2476-2485; Diabetes Care 2013;36:750-759]
“In conclusion, in a population-based sample of Malay adults, we found that the presence of retinal microvascular changes including smaller retinal arterioles, larger retinal venules and presence of retinopathy were associated with increased risk of CKD,” they concluded.