Plasma Erythritol Levels and Renal Function Decline in Patients with Type 2 Diabetes: A Retrospective Cohort Study with In Vitro Experiments

Background/Objectives: Circulating erythritol has been linked to cardiometabolic disorders, but its association with renal function decline remains unclear. We investigated this association in patients with type 2 diabetes and examined the effects of erythritol on interleukin-6 (IL-6) secretion from tubular cells. Methods: This retrospective study included 217 patients with baseline estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2. Plasma erythritol and IL-6 concentrations were measured. Renal outcomes were defined as an annual change in eGFR < −2.5 mL/min/1.73 m2 and an eGFR reduction > 30%. Multivariable logistic regression analyses were performed. Human renal proximal tubular epithelial cells (RPTECs) were treated with erythritol for 24 h. Results: Median follow-up was 50 months. Plasma erythritol concentrations were positively correlated with cardio-ankle vascular index, total plaque score, and plasma IL-6 concentrations, and inversely correlated with baseline eGFR. Among 196 patients with eGFR ≥ 60 mL/min/1.73 m2, higher erythritol concentrations were independently associated with Criterion 1 after adjustment for age, sex, body mass index, eGFR, and urinary albumin-to-creatinine ratio. Erythritol increased IL-6 secretion from RPTECs at 1 and 10 μmol/L. Conclusions: Plasma erythritol may serve as a functional biomarker and risk marker for subsequent renal function decline in patients with type 2 diabetes and relatively preserved kidney function. Its association with plasma IL-6 concentrations and its effects on RPTEC IL-6 secretion suggest a potential link between erythritol and renal tubular inflammation.