Prior research suggests that biological age, a measure of the body’s functional capability, is an accurate indicator of age-related morbidity and mortality in end-stage kidney disease (ESKD). “Complications from kidney failure can be burdensome for patients and healthcare professionals, highlighting the need for early diagnosis and prevention,” says Zhuoting Zhu, MD, PhD. “Unfortunately, few biomarkers have been identified to help distinguish people at higher risk for kidney failure.”

The retina has long been considered a window into the kidney because of similarities in microvascular structures, as well as physiologic and pathogenic pathways. “Previous studies have demonstrated strong associations between eye and kidney conditions like cataracts and ESKD,” Dr. Zhu adds. This means there is potential for retinal imaging to be used as a fast, safe, non-invasive, and cost-effective way to supplement screening for kidney disease. As artificial intelligence systems continue to improve how retinal photographs are interpreted, it is possible these images can help predict kidney function.

Impact of Retinal Age on Mortality & Comorbidities

Previously, Dr. Zhu and colleagues developed and validated a deep learning system that accurately predicted chronological age in a healthy population based on fundus images. “Powered by artificial intelligence, we recently found that retinal age—defined as biological age based on retinal images was a promising aging biomarker,” says Dr. Zhu. “The retinal age gap, which is the difference between retinal age and actual age, was also associated with risks for death and age-related comorbidities.”

For a study published in the American Journal of Kidney Diseases, Dr. Zhu and colleagues investigated associations between the retinal age gap and future risk for incident ESKD. “Our findings were based on data from a total of 35,864 participants from the UK Biobank study who were free of kidney disease at their baseline examinations,” Dr. Zhu says.

Larger Retinal Age Gap Raises Risk for Incident ESKD

After a follow-up of 11 years, 115 participants (0.32%) were diagnosed with ESKD. When compared with the non-ESKD group, patients diagnosed with ESKD tended to be older, male, and White. Those diagnosed with ESKD were also more likely to be smokers, alcohol consumers, and have higher BMIs and cholesterol levels. Furthermore, these individuals more frequently had a history of diabetes and hypertension and worse overall general health.

“A key finding was that a larger retinal age gap was significantly associated with higher risk for future kidney failure,” says Dr. Zhu. “Each 1-year increase in retinal age gap was independently associated with a 10% increase in the risk for incident ESKD.” This association remained significant after further adjustments (Table). In fully adjusted models, each 1-year increase in the retinal age gap was associated with 8% and 13% increases in the risk for incident ESKD in men and women, respectively. Both men and women with retinal age gaps in the fourth quartile the highest risk group had a 2.77-fold higher risk for incident ESKD than those in the first quartile, the lowest risk group.

Retinal Age Gap an Early Biomarker for ESKD

Biomarker for ESKD The low rates of early ESKD diagnoses combined with the high morbidity and mortality associated with delayed interventions make it critical to identify people at a high risk for ESKD. “Our findings indicate that retinal age gap itself may be a novel early biomarker for kidney failure,” Dr. Zhu says. “The retinal age gap is non-invasive, user-friendly, cost-effective, and readily accessible in many healthcare settings. The retinal age gap offers opportunities [to those who manage kidney disease] for largescale screening and can assist in the management of kidney failure by allowing for early detection and prevention and personalized interventions. In addition, advancements to retinal imaging, such as full automated and smartphone-based cameras, may extend the clinical utility of the retinal age gap.”

More studies are needed to investigate links between dynamic changes in retinal age gap with incident ESKD to evaluate its predictive value. The study team plans to further explore the clinical value of retinal age gap in more diverse racial/ethnic groups. “In future research, we also plan to seamlessly integrate retinal age gap into real-world clinical settings where kidney conditions are managed,” says Dr. Zhu.