Choroidal and Retinal Thinning in CKD Are Modifiable with Treatment and Independently Associate with eGFR Decline

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Background: Cardiovascular disease is the commonest complication of chronic kidney disease (CKD). As estimated glomerular filtration rate (eGFR) declines, cardiovascular risk increases. There is an unmet need for novel biomarkers that reliably track kidney injury, demonstrate treatment-response, and predict patient outcomes. We investigated the ability of retinal optical coherence tomography (OCT) to achieve these ends. Methods: Patients with stable, pre-dialysis CKD (including those with a kidney transplant), patients with kidney failure undergoing kidney transplantation, living kidney donors, and healthy volunteers were recruited into a series of prospective, cross-sectional, and longitudinal studies. We used the SPECTRALIS OCT machine to examine retinal thickness, macular volume, and choroidal vascular layer thickness. Results: Compared to healthy volunteers, macular volume was reduced in CKD patients (health vs. CKD: 8.73±0.36 mm3vs. 8.44±0.44 mm3, p <0.001). Kidney transplant recipients also had a reduced macular volume compared to health of a similar magnitude to that seen in CKD patients. The choroid was thinner in CKD patients (health vs. CKD, macular locations I, II and III: 234±80mm vs. 197±85mm, 319±93mm vs. 274±93mm, 292±83mm vs. 262±84mm, p <0.01 for each). Conversely, patients with a kidney transplant had choroidal thicknesses similar to healthy levels, suggesting reversal of thinning. In those with CKD, the degree of choroidal thinning related to increasing age (r= -0.25, p =0.008), falling eGFR (r=0.30, p =0.001) and severity of kidney scarring (r= -0.60, p <0.001). Patients undergoing kidney transplantation (n=25) demonstrated rapid choroidal thickening (˜10%) that was maintained at 1-year post-transplant. These patients also demonstrated increases in both retinal thickness and macular volume over this period. Conversely, kidney donors (n=22) demonstrated gradual choroidal thinning over 1-year but there were no changes in retinal thickness or macular volume. In patients with CKD (n=289), both retinal and choroidal thickness independently associated with eGFR decline over 2 years. Conclusions: These observations highlight the potential for retinal OCT to act as a non-invasive monitoring and prognostic biomarker of kidney injury. Larger, longer-term clinical trials are now warranted. Funding: Government Support - Non-U.S.

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