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Diabetic kidney disease (DKD) is a common complication of diabetes mellitus (DM) that may not be diagnosed until later stages of disease. Ways to improve non-invasive screening for DKD are desirable. Kidney cell exfoliation into urine is an active process, which may generate significant information regarding an individual’s kidney status. Proximal tubule cell (PTC) exfoliation could also be useful within the DM context as glucose entry into PTCs is insulin independent, making PTCs particularly sensitive to hyperglycemia in diabetic conditions. Early studies demonstrated increased numbers of exfoliated kidney cells in diabetic patients with retinopathy compared to those without retinopathy. However, it remains unclear to date whether the number of exfoliated PTCs in urine is associated with diabetic severity and DKD. Our study aims to explore this further.
Adults (age ≥ 18 years) without DM, and those with Type 1 and 2 DM with and without overt DKD were included. Urine samples were collected and stored at -80 degrees. On assessment, exfoliated PTCs were extracted from thawed urine using a validated specific immuno-magnetic separation method based on anti-CD13 and anti-SGLT2-antibodies. Brightfield microscopy was used to visualize the number of PTCs present. Patient demographic information alongside clinical and biochemical data were recorded and summarized using appropriate descriptive statistics. To assess effects of DM on the number of urinary exfoliated PTCs and adjusting for co-variates, a Poisson regression analysis model was constructed. The model incorporated formally diagnosed DM status, eGFR (ml/min/1.73m2), age (years), gender, ethnicity, HbA1c%, body mass index, urine volume (ml) collected from patient, urine albumin-to-creatinine ratio, serum creatinine, systolic blood pressure (mmHg), diastolic blood pressure (mmHg), history of cardiovascular events and retinopathy as predictors. Incidence rate ratio (IRR) with corresponding 95% confidence intervals (95% CIs) and p-values (p < 0.05 is significant) were calculated to determine the significance of association. Analysis was performed in STATA (version 17.0).
122 individuals were included in our study between Jan 2019 and May 2023, including 38 non-DM and 84 individuals diagnosed with Type 1 or 2 DM. Mean age overall was 59.9 years (standard deviation 14.31), with majority of the cohort being male (70.5%). Evaluating results from our statistical model, each 1% increase in HbA1c% is associated with an increase of 1.37 times in mean exfoliated PTCs (IRR 1.37, 95%CI 1.10-1.71, p = 0.005). Median eGFR were significantly lower (52 vs 66 ml/min/1.73m2, p = 0.004), and median serum creatinine levels were significantly higher (115.5 vs 96, p = 0.028) in the DM group compared to the non-DM group.
Our results indicate increased shedding of PTCs into the urinary tract increases in patients with poor glycemic control and with established DKD. Additional research is required to evaluate the pathophysiological mechanisms that underpin these observations. Further studies with larger cohorts are also needed to determine whether the number of urinary exfoliated PTCs can be applied as a clinically useful marker to prognosticate DKD progression over time.