Albuminuria, but not eGFR, tracks diabetic retinopathy severity and retinal ischemia: population-based discovery, clinical replication, and OCTA evidence.
We investigated whether albuminuria is more consistently associated with diabetic retinopathy (DR) severity than estimated glomerular filtration rate (eGFR) and whether it corresponds to an ischemic retinal phenotype on optical coherence tomography angiography (OCTA).
This two-part cross-sectional study first analyzed 949 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) to evaluate the associations of albumin-to-creatinine ratio (ACR) and eGFR with the DR outcomes. An independent single-center cohort of 168 adults with type 2 diabetes, including a nested 134-participant OCTA subset, was then used to examine the associations of urine ACR (UACR) and eGFR with the clinical DR endpoints and retinal perfusion metrics.
In the NHANES, each doubling of ACR was independently associated with higher odds of AnyDR and SevereDR, with stronger association for SevereDR (odds ratio, OR = 1.30), whereas eGFR showed no independent association. In the clinical cohort, each doubling of UACR was associated with higher odds of moderate-or-worse DR and vision-threatening diabetic retinopathy (VTDR) (OR = 2.86 and 2.70, respectively), while eGFR remained non-significant. In the OCTA subset, a higher UACR was associated with greater widefield non-perfusion and lower macular perfusion density, whereas eGFR was not associated with either OCTA endpoint.
Across the studied cohorts, albuminuria was consistently associated with more severe DR and an ischemic OCTA phenotype, whereas eGFR did not show an independent association within the observed kidney function range. Spot urine ACR testing may serve as a practical biomarker for stratifying retinal microvascular ischemia risk.
This two-part cross-sectional study first analyzed 949 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) to evaluate the associations of albumin-to-creatinine ratio (ACR) and eGFR with the DR outcomes. An independent single-center cohort of 168 adults with type 2 diabetes, including a nested 134-participant OCTA subset, was then used to examine the associations of urine ACR (UACR) and eGFR with the clinical DR endpoints and retinal perfusion metrics.
In the NHANES, each doubling of ACR was independently associated with higher odds of AnyDR and SevereDR, with stronger association for SevereDR (odds ratio, OR = 1.30), whereas eGFR showed no independent association. In the clinical cohort, each doubling of UACR was associated with higher odds of moderate-or-worse DR and vision-threatening diabetic retinopathy (VTDR) (OR = 2.86 and 2.70, respectively), while eGFR remained non-significant. In the OCTA subset, a higher UACR was associated with greater widefield non-perfusion and lower macular perfusion density, whereas eGFR was not associated with either OCTA endpoint.
Across the studied cohorts, albuminuria was consistently associated with more severe DR and an ischemic OCTA phenotype, whereas eGFR did not show an independent association within the observed kidney function range. Spot urine ACR testing may serve as a practical biomarker for stratifying retinal microvascular ischemia risk.