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First page of Preservation of Urinary Podocyte Markers in Diabetic Kidney Disease by SGLT2 Inhibitor Therapy

Background Sodium glucose cotransporter 2 inhibitor (SGLT2i) is a standard treatment for kidney and cardiovascular protection in diabetic kidney disease (DKD). We investigated the effect of SGLT2i on the urinary podocyte-associated molecules levels in DKD. Methods We studied 24 DKD patients who were started on SGLT2i treatment and 25 patients who were not treated (control group). Urinary levels of podocyte-associated molecules, their corresponding mRNA levels in urinary sediment, estimated glomerular filtration rate (eGFR), and urine albumin-creatinine ratio (UACR) were measured at baseline and 3 months later. Results Urinary levels of podocin, podocalyxin, and synaptopodin increased significantly over 3 months in the control group, while the levels remained static in the treatment group. After 3 months of treatment, urinary podocin (2.95 [0.92-5.45] vs 9.15 [1.88-24.80] ng/mol-Cr, p <0.01), podocalyxin (367.3 [299.5-768.6] vs 920.6 [369.3-2060.4] ng/mol-Cr, p <0.01), and synaptopodin levels (13.17 [9.86-47.02] vs 35.56 [17.59-134.08] ng/mol-Cr, p <0.05) were significantly lower in the treatment than the control group. Urinary sediment mRNA levels of podocin, podocalyxin, synaptopodin, and nephrin did not change in both groups. However, there was no significant correlation between urinary podocyte-associated marker levels and eGFR or UACR at baseline or after treatment. Conclusions SGLT2i prevent the progressive increase in the urinary excretion of podocyte-specific molecules in DKD patients, suggesting that SGLT2 inhibitors has a protective effect to the podocytes.

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2025
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