499-P: Association between Diabetic Retinopathy and Number of Urinary Exfoliated Proximal Tubule Kidney Cells

Introduction & Objective: Emerging evidence suggests cell exfoliation could be operating under the control of cell metabolism. Recent studies indicate kidney cell exfoliation into urine may reflect metabolic status. Proximal tubule cell (PTC) exfoliation can be particularly sensitive to hyperglycemia in diabetes mellitus (DM) as glucose entry into PTCs is insulin independent. While it appears that number of urinary exfoliated PTCs increases with DM, it is unclear if there are associations between number of exfoliated PTCs with diabetic severity and co-morbidities. Our study aims to explore this.

Methods: Adults age ≥ 18 yrs with type 1 or 2 DM were included. Collected urine samples were stored at -80°C. On assessment, exfoliated PTCs were extracted from thawed urine using a validated specific immunomagnetic separation method based on anti CD13 and anti SGLT2 antibodies. Number of PTCs present was visualized using brightfield microscopy. A Poisson regression model adjusting for HbA1c%, eGFR (ml/min/1.73m²), presence of diabetic retinopathy (DR), cardiovascular events (CVE) history, age (yrs), sex, ethnicity, BMI, urine volume (ml) collected, estimated urinary creatinine clearance rate, serum creatinine, uACR and blood pressure (mmHg) as variables was constructed to determine association with mean exfoliated PTCs. Incidence rate ratios (IRR) determined significance of association.

Results: Eighty four patients with DM were included. Mean age is 63.8 yrs (std dev 11.6) and 81% are male. Each 1% increase in HbA1c% was associated with an increase of 1.03 times in mean exfoliated PTCs (IRR 1.03, 95%CI 1.01-1.04, p=0.007). Presence of DR was associated with an increase of 1.68 times in mean exfoliated PTCs (IRR 1.68, 95%CI 1.07-2.62, p=0.024). There were no significant associations between eGFR or CVE history with mean exfoliated PTCs.

Conclusion: Our results indicate increased shedding of PTCs into the urinary tract in patients with DM with poorer glycemic control and presence of DR.