Effects of empagliflozin on biomarkers of renal injury, fibrosis and low-grade inflammation in patients with type 2 diabetes

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been implemented into the treatment standards for chronic kidney disease (CKD) in patients with type 2 diabetes (T2D). Identification of predictors of the protective effect of SGLT2 inhibitors on the kidneys remains an urgent task.

AIM: To evaluate the effects of the SGLT2 inhibitor empagliflozin on the levels of biomarkers of renal injury, fibrosis and low-grade inflammation in patients with T2D with CKD and/or high cardiovascular risk.

MATERIALS AND METHODS: This prospective cohort single-center study included 30 patients with T2D newly initiated treatment with an SGLT2 inhibitor. Before and on day 90 of treatment with empagliflozin (10 mg/day), urinary excretion of nephrin, retinol-binding protein 4 (RBP-4), type IV collagen, and fibrosis marker WFDC-2, as well as serum concentrations of high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor receptor 1A alpha (TNFRSF1A) were determined by ELISA. Twenty healthy individuals were included in the control group.

RESULTS: Patients with T2D compared to controls initially demonstrated higher excretion of nephrin (p=0.03), RBP-4 (p=0.001), type IV collagen (p=0.04) and WDFC-2 (p=0.02), as well as higher serum concentrations of hsCRP and TNFSF1A (p=0.03). Empagliflozin treatment was associated with a significant decrease in the excretion of RBP-4 (p=0.04) and TNFRSF1A levels (p<0.001). Excretion of nephrin, type IV collagen, WFDC-2 and hsCRP levels did not change significantly (p>0.05). Baseline RBP-4 excretion and serum TNFRSF1A levels were associated with changes in creatinine levels during empagliflozin treatment.

CONCLUSION: In patients with T2D with CKD and/or high cardiovascular risk, empagliflozin treatment resulted in decreased urinary excretion of RBP-4 and serum TNFRSF1A levels. These data may indicate a protective effect of empagliflozin on tubular dysfunction and low-grade inflammation.

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