Supplementary Material for: 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.

背景 钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）是糖尿病肾病（DKD）患者肾脏与心血管保护的标准治疗方案。本研究探讨了SGLT2i对糖尿病肾病患者尿足细胞相关分子水平的影响。
方法 本研究纳入24例起始接受SGLT2i治疗的糖尿病肾病患者，以及25例未接受治疗的患者（对照组）。分别于基线状态及治疗3个月后，检测受试者的尿足细胞相关分子水平、尿沉渣中对应分子的mRNA表达水平、估算肾小球滤过率（eGFR）以及尿白蛋白肌酐比值（UACR）。
结果 对照组患者的尿足盂蛋白（podocin）、足细胞抗原（podocalyxin）和突触足蛋白（synaptopodin）水平在3个月随访期内显著升高，而治疗组患者的上述分子水平无明显变化。治疗3个月后，治疗组患者的尿足盂蛋白[2.95（0.92~5.45）vs 9.15（1.88~24.80）ng/μmol-Cr，p<0.01]、足细胞抗原[367.3（299.5~768.6）vs 920.6（369.3~2060.4）ng/μmol-Cr，p<0.01]及突触足蛋白[13.17（9.86~47.02）vs 35.56（17.59~134.08）ng/μmol-Cr，p<0.05]水平均显著低于对照组。两组患者尿沉渣中足盂蛋白、足细胞抗原、突触足蛋白及肾裂孔蛋白（nephrin）的mRNA表达水平均无显著变化。此外，无论在基线还是治疗3个月后，尿足细胞相关标志物水平与估算肾小球滤过率或尿白蛋白肌酐比值均无显著相关性。
结论 SGLT2i可阻止糖尿病肾病患者尿足细胞特异性分子排泄量的进行性升高，提示SGLT2抑制剂对足细胞具有保护作用。