Associations of Biomarkers of Kidney Tubule Health with Retinal Microvascular Signs: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background: CKD is strongly associated with cardiovascular disease (CVD), yet the etiology responsible for this link remains elusive. Novel blood and urine biomarkers reflecting kidney tubule dysfunction and injury may provide novel insights to mechanisms linking the kidney to CVD.

Methods: In 470 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) without type 2 diabetes, CVD or CKD, we measured six plasma (kidney injury molecule-1 [KIM-1], monocyte chemoattractant protein-1 [MCP-1], soluble urokinase plasminogen activator receptor [suPAR], tumor necrosis factor receptor [TNFR] 1 and 2, and anti-chitinase-3-like protein 1 [YKL-40]) and six urinary (alpha 1 microglobulin [A-1M], epidermal growth factor [EGF], KIM-1, MCP-1, YKL-40 and uromodulin [UMOD]) kidney tubule health biomarkers. To assess microvascular health, we used retinal microvascular measurements assessed from fundus photography: central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively). Multivariable linear regression evaluated associations of tubule biomarkers and kidney function with CRAE and CRVE.

Results: The mean participant age was 60 ± 10 years with 52% female. The racial/ethnic distribution was 46% White, 24% African American, 18% Hispanic, and 11% Chinese. The mean eGFR was 92.1 ± 13.3 mL/min/1.73m2, and the median urine ACR was 4.7 mg/g (IQR 3.0, 9.4). Higher plasma KIM-1 (β -5.14, 95% confidence interval [95% CI], -9.84 to -0.45), and urine KIM-1 (β -5.68, 95% CI, -10.15 to -1.22) concentrations were individually associated with narrower CRAE, while plasma suPAR concentrations were individually associated with wider CRAE (β 9.15, 95% CI, 0.89 to 17.4) and CRVE (β 21.49, 95% CI, 9.39 to 33.59). There were no significant associations between the remaining tubule health biomarkers and CRAE or CRVE, nor were there associations between eGFR or urine ACR with CRAE and CRVE.

Conclusions: In this study of community-living individuals without CKD, diabetes, or CVD, selected kidney tubule health markers are associated with retinal microvascular changes. These findings suggest that kidney tubules biomarkers may reflect or contribute to systemic microvascular dysfunction, above and beyond glomerular damage. Tubular biomarkers may help elucidate the shared microvascular mechanisms linking CKD and CVD.