A systematic review and participant-level meta-analysis found little association of retinal microvascular caliber with reduced kidney function

Abstract

Previously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular caliber and CKD. A systematic review was performed using Medline and EMBASE for articles published until October 2018. The aggregate analysis used a two-stage approach combining summary estimates from eleven studies (44,803 patients) while the individual participant analysis used a one-stage approach combining raw data from nine studies (33,222 patients). CKD stages 3-5 was defined as an estimated glomerular filtration rate under 60 mL/min/1.73m². Retinal arteriolar and venular caliber (central retinal arteriolar and venular equivalent) were assessed from retinal photographs using computer-assisted methods. Logistic regression estimated relative risk of CKD stages 3-5 associated with a 20 μm decrease (approximately one standard deviation) in central retinal arteriolar and venular equivalent. Prevalence of CKD stages 3-5 was 11.2% of 33,222 and 11.3% of 44,803 patients in the individual participant and aggregate data analysis, respectively. No significant associations were detected in adjusted analyses between central retinal arteriolar and venular equivalent and CKD stages 3-5 in the aggregate analysis for central retinal arteriolar relative risk (0.98, 95% confidence interval 0.94-1.03); venular equivalent (0.99, 0.95-1.04) or individual participant central retinal arteriolar (0.99, 0.95-1.04) or venular equivalent (1.01, 0.97-1.05). Thus, meta-analysis provided little evidence to suggest that cross sectional direct measurements of retinal vascular caliber was associated with CKD stages 3-5 in the general population. Hence, meta-analyses of longitudinal studies evaluating the association between retinal parameters and CKD stages 3-5 may be warranted.

Keywords: biomarker; caliber; chronic kidney disease; microvasculature; retina.

Figure 1.

Study selection and data extraction. Abbreviations: ARIC, Atherosclerosis Risk in Communities Study; BMES, Blue Mountains Eye Study; CHS, Cardiovascular Health Study; MESA, Multi-Ethnic Study of Atherosclerosis; SCES, Singapore Chinese Eye Study; SiMES, Singapore Malay Eye Study; SINDI, Singapore Indian Eye; SP2, Singapore Prospective Study.

Figure 2.

Forest plots showing the association between a 20μm decrease in central retinal arteriolar equivalent (CRAE) and CKD stages 3–5 for studies included in the two-stage aggregate data random effects meta-analysis (Model 3). Model 3: Adjusted for age and sex, ethnicity (if multi-ethnic), education, current smoking, diabetes, hypertension, body mass index, total cholesterol, and fellow vessel central retinal arteriolar equivalent. *Multivariable model did not include education. Abbreviations: RR Relative risk; Standard error (SE); 95% Confidence Intervals (95% CI); ARIC, Atherosclerosis Risk in Communities Study; BDES, Beaver Dam Eye Study; BMES, Blue Mountains Eye Study; CHS, Cardiovascular Health Study; MESA, Multi-Ethnic Study of Atherosclerosis; SCES, Singapore Chinese Eye Study; SiMES, Singapore Malay Eye Study; SINDI, Singapore Indian Eye; SP2, Singapore Prospective Study Programme.

Figure 3.

Forest plots showing the association between a 20μm decrease in central retinal venular equivalent (CRVE) and CKD stages 3–5 for studies included in the two-stage aggregate data random effects meta-analysis (model 3). Model 3: Adjusted for age and sex, ethnicity (if multi-ethnic), education, current smoking, diabetes, hypertension, BMI, total cholesterol, and fellow vessel central retinal arteriolar equivalent. *Multivariable model did not include education. Abbreviations: RR Relative risk; Standard error (SE); 95% Confidence Intervals (95% CI); ARIC, Atherosclerosis Risk in Communities Study; BDES, Beaver Dam Eye Study; BMES, Blue Mountains Eye Study; CHS, Cardiovascular Health Study; MESA, Multi-Ethnic Study of Atherosclerosis; SCES, Singapore Chinese Eye Study; SiMES, Singapore Malay Eye Study; SINDI, Singapore Indian Eye; SP2, Singapore Prospective Study Programme.