This is the first comprehensive study of retinal pathology in a cohort of CKD patients with a wide range of kidney dysfunction. Our findings show a significant association between worse ETDRS retinopathy scores and lower eGFR. This association remains significant after adjustment for both traditional and non-traditional CKD risk factors, suggesting that severity of retinopathy provides additional information on severity of CKD. The association is stronger among participants previously diagnosed with diabetes. Non-diabetic participants with retinopathy have lower eGFR, but not to a statistically significant degree. Other studies have shown associations between retinal and kidney disease, but without adjustment for the high number of risk factors included in this analysis. 2,7, 17
Most of the retinopathy features contributing to the ETDRS score were associated with lower kidney function when considered without regard to other retinopathy features (). Multivariate analyses demonstrated that retinal hemorrhage count and intraretinal microvascular abnormalities were independently associated with lower eGFR (). Arteriolar sheathing, caused by hypertension, was associated with lower eGFR, whereas there was no association with arterio-venous abnormalities, also thought to be caused by hypertension.
Our findings support the hypothesis that common mechanisms may cause both retinal and renal vascular changes8
. Retinal pathologic features are associated with inflammatory processes,18,19,
and endothelial dysfunction,18
leading to circulatory abnormalities and reduced vascular reactivity.20,21
Both retinopathy and nephropathy involve thickening of basement membrane17
and muscular layers and increased leakage.22
These pathologic and hemodynamic abnormalities may occur throughout the body and their effects on the retinal vasculature may be useful indicators of cumulative microvascular damage from hypertension, inflammation, diabetes and other processes.18,23,24
Furthermore, a recent study has suggested common inherited susceptibilities to retinopathy and CKD in diabetic patients.25
The results of our study show only a marginal association between retinal venular caliber and kidney function that could be due to limited power. Although the relationship was not monotonic, in general smaller venular caliber was weakly associated with lower eGFR, and adjustment for traditional and novel factors weakened the associations. No such relationships were seen when participants with diabetes mellitus were assessed separately (data not shown). Retinal venular dilatation has been associated with progression of diabetic retinopathy26, poor glycemic control27
, obesity, inflammation and endothelial dysfunction.18
Possibly, the effects of reduced kidney function may counteract the effects of diabetes mellitus on vascular diameter, and therefore, no strong association between eGFR and venular calibers was observed.
Several studies have shown arteriolar narrowing related to current and past blood pressure. 28–30
Similar changes have been observed in myocardial arterioles31,32
and kidney arterioles.33
We detected no significant association in our study between retinal arteriolar caliber and eGFR (). The fact that nearly 90% of our study group was hypertensive with most on medications may have blunted an association. Sabanayagam34
found a cross-sectional association between arteriolar narrowing and lower eGFR in one study but did not detect an association with risk for progression of CKD.33
The fact that some of the participants of our study had ungradable photographs is a limitation of our study. Ungradable photographs, however, were associated with decreased renal function. Decreased media clarity by cataracts, vitreous hemorrhage, retinal detachment, and small pupils contribute to poor photographic quality. In addition, ill patients are less likely to sit quietly and maintain fixation. Another study has reported that eyes with ungradable photographs have more eye pathology13
, suggesting that there is important information in the fact that photos are ungradable.
One must be cautious in the interpretation of our results. We cannot exclude the possibility that the relationship between retinopathy and eGFR is driven by a direct damage of hypertension on the retinal vasculature. Although we have used current systolic blood pressure as a covariate for our adjustments, it is possible that this relationship is confounded by the history of hypertension, which is not fully addressed in this study. In addition, we do not have a good characterization of the cause of kidney disease to be able to assess the impact of this factor on the relationship between retinopathy and eGFR.
In summary our study demonstrates a strong association between retinopathy and decreased kidney function, highlighting the need for eye evaluations in patients with CKD. Our data are consistent with the hypothesis that retinovascular pathology may reflect renal vascular pathology, although they do not prove this relationship because of the cross sectional nature of our study. Further investigations are needed in order to evaluate whether presence of retinopathy in patients with CKD offers information of prognostic value regarding accelerated loss of kidney function.