Associations between retinal microvascular abnormalities and declining renal function in the elderly population: The Cardiovascular Health Study

Background: Microvascular abnormalities in the kidney are common histopathologic findings in individuals with chronic kidney disease or renal failure. These abnormalities may represent one manifestation of ongoing systemic microvascular damage. We hypothesized that retinal microvascular abnormalities, when present, would be associated with progressive renal dysfunction in elderly individuals. Methods: The Cardiovascular Health Study (CHS) is a prospective, multicenter, cohort study initiated in 1989 designed to examine cardiovascular risk factors, morbidity, and mortality in elderly Americans. As part of an ancillary study, CHS participants underwent retinal photography in 1997 and 1998. Retinal microvascular abnormalities were assessed and graded by using standardized measures. Retinal microvascular abnormalities were defined as retinopathy (hard and soft exudates, hemorrhages, or microaneurysms) and/or retinal arteriolar abnormalities (arteriovenous nicking, focal arteriolar narrowing, or lowest quartile arteriole-venule ratio). Associations between these abnormalities and observed 4-year changes in serum creatinine levels and estimated glomerular filtration rates (eGFRs) from study years 5 to 9 (encompassing years 1994 to 2001) were examined by using regression modeling. Results: A total of 1,394 CHS participants had retinal and serum creatinine data. After adjustments for age, race, sex, weight, diabetes, hypertension, angiotensin-converting enzyme inhibitor use, and proteinuria, participants with retinopathy showed a significant increase in serum creatinine level and decline in eGFR compared with those without retinopathy during the 4-year study period (+0.24 mg/dL [+21 mu mol/L] versus -0.21 mg/dL [-19 mu mol/L] and -0.48 mL/min/1.73 m(2) [-0.01 mL/s/1.73 m(2)] versus +1.74 mL/min/1.73 m(2) [+0.03 mL/s/1.73 m(2)], respectively). Participants with retinopathy also were significantly more likely to have an observed significant deterioration in renal function, defined as a 0.3-mg/dL (27-mu mol/L) increase in serum creatinine level or 20% or greater decline in eGFR (odds ratio, 3.20; 95% confidence interval, 1.58 to 6.50; and odds ratio, 2.84; 95% confidence interval, 1.56 to 5.16, respectively). These associations remained in separate stratified analyses of patients with and without diabetes. The presence of retinal arteriolar abnormalities was not associated with deteriorating renal function. Conclusion: Retinal microvascular abnormalities defined as retinopathy were significantly associated with renal function deterioration. The observed findings were independent of effects of any associated diabetes or hypertension. These findings suggest that systemic microvascular disease may be associated with progressive renal dysfunction in the elderly population.