Retinopathy Provides Window Into Chronic Kidney Disease

Damian McNamara

September 26, 2012

September 26, 2012 — The primary role of the retina is to capture light and create sight, but adverse changes to the retina may also signal important alterations to the kidneys.

Using photographs of the retina collected from 1820 patients with renal disease, Juan E. Grunwald, MD, from the Department of Ophthalmology at the University of Pennsylvania School of Medicine in Philadelphia, and colleagues found a significant association between the presence of retinopathy and chronic kidney disease as measured by lower estimated glomerular filtration rate (eGFR; P < .001). They reported the findings from this multicenter, cross-sectional study in an article published in the September issue of the Archives of Ophthalmology.

"The results of this study suggest that by examining the eyes, physicians may gain knowledge about renal disease. Since eye photography is a noninvasive and relatively inexpensive procedure, this may be a good way of obtaining information on renal disease," Dr. Grunwald said in an interview with Medscape Medical News.

The current Retinopathy in Chronic Renal Insufficiency Cohort (RCRIC) study builds on previous findings from CRIC investigators, who previously have demonstrated almost half of patients had fundus pathology associated with chronic kidney disease risk factors. In this secondary study, investigators evaluated retinal photographs of 1936 adults with chronic kidney disease taken from June 2006 to May 2008. A total 1820 patients were gradable and assessed further.

The authors noted pathology, measured the diameter of the major retinal arterioles and venules, and assigned a retinopathy severity score to each eye, using Early Treatment of Diabetic Retinopathy Study (ETDRS) criteria.

According to the investigators, this is the first report of an association between retinopathy and decreased renal function that includes patients with a wide range of kidney dysfunction etiologies (not limited to diabetes or hypertension). It also is the first to demonstrate a significant association between retinopathy and a lower eGFR after controlling for a large number of chronic kidney disease risk factors.

"I was surprised that we found associations that remained significant even after we adjusted for known traditional and nontraditional risk factors," Dr. Grunwald said. Because the study was cross-sectional, it was not possible to determine whether the retinopathy or the chronic kidney disease develops first, he added.

In an initial multivariate analysis, researchers assessed traditional risk factors including age, race/ethnicity, systolic blood pressure, presence of diabetes mellitus, and 24-hour urine protein measurement. In a second multivariate analysis, the researchers controlled for these as well as nontraditional chronic kidney disease risk factors such as anemia, use of angiotensin receptor blockers, self-reported cardiovascular disease, body mass index, cyclase-activating parathyroid hormone level, and smoking status.

"The study was well-conducted," Jie Jin Wang, MBBS, MMed (Ophth Path), MMed (Clin Epi), PhD, MApplStat, from the Department of Clinical Ophthalmology and Eye Health at the University of Sydney in Australia, said when asked to comment. "The copresence of retinopathy and chronic kidney disease in these subjects is highly likely a signal of small vessel or microvasculature damage from a common pathology, such as diabetes or hypertension." She added that half of the adults with chronic kidney disease in the study had diabetes, which is relevant to interpretation of the results.

A higher proportion of participants with diabetes mellitus had retinopathy (49% of 925 patients with diabetes) compared with only 11% of 1011 participants without diabetes. This difference was statistically significant (P < .001). However, diabetes did not significantly alter the association between retinopathy and decreased eGFR (P = .75).

Dr. Wang, who was not involved in the study, told Medscape Medical News that the study reinforces the message that retinopathy and nephropathy are the 2 manifestations of small vessel damage that are readily detectable clinically.

Dr. Grunwald and colleagues also found that the severity of retinopathy plays a role. Participants without retinopathy had the highest eGFR rates, and not surprisingly, those with the most proliferative retinopathy had the lowest eGFR values. The association between worse ETDRS retinopathy scores and lower eGFR remained significant after adjustment for both traditional and nontraditional risk factors (P = .005).

In contrast, Dr. Grunwald and colleagues found no significant association between eGFR and retinal arteriolar caliber measurements (P = .41).

Ungradable photographs from 116 participants were a potential limitation of the study. In addition, although they controlled for systolic blood pressure, an inability to rule out direct damage on the retinal vasculature from current or previous hypertension is another potential limitation, the authors note.

In terms of future research, Dr. Wang suggests studies to confirm the utility and value of retinal examinations to detect small vessel disease.

Dr. Grunwald said prognosis is an unanswered question: "We are now investigating whether the presence of retinopathy in patients with chronic kidney disease may provide information of prognostic value regarding future progression of kidney and heart disease."

This study was funded by grants from the National Institutes of Health, by the Vivian S. Lasko Research Fund, by the Nina C. Mackall Trust, and by Research to Prevent Blindness. One coauthor is a consultant for Roche, GlaxoSmithKline, and NiCox. One coauthor has a contract with RTI International Amgen. The other authors and Dr. Wang have disclosed no relevant financial relationships.

Arch Ophthalmol. 2012;130:1136-1144. Abstract