Cherney David, Perkins Bruce A, Lytvyn Yuliya, Heerspink Hiddo, Rodríguez-Ortiz María E, Mischak Harald
Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada.
Division of Endocrinology, University Health Network, University of Toronto, Toronto, Canada.
PLoS One. 2017 Oct 30;12(10):e0186910. doi: 10.1371/journal.pone.0186910. eCollection 2017.
Treatment with empagliflozin, an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), is associated with slower progression of diabetic kidney disease. In this analysis, we explored the hypothesis that empagliflozin may have an impact on urinary peptides associated with chronic kidney disease (CKD). In this post-hoc, exploratory analysis, we investigated urine samples obtained from 40 patients with uncomplicated type 1 diabetes (T1D) before and after treatment with empagliflozin for 8 weeks to for significant post-therapy changes in urinary peptides. We further assessed the association of these changes with CKD in an independent cohort, and with a previously established urinary proteomic panel, termed CKD273. 107 individual peptides significantly changed after treatment. The majority of the empagliflozin-induced changes were in the direction of "CKD absent" when compare to patients with CKD and controls. A classifier consisting of these 107 peptides scored significantly different in controls, in comparison to CKD patients. However, empagliflozin did not impact the CKD273 classifier. Our data indicate that empagliflozin induces multiple significant changes in the urinary proteomic markers such as mucin and clusterin. The relationship between empagliflozin-induced proteomic changes and clinical outcomes merits further investigation.
钠/葡萄糖协同转运蛋白2（SGLT2）抑制剂恩格列净治疗与糖尿病肾病进展较慢相关。在本分析中，我们探讨了恩格列净可能对与慢性肾脏病（CKD）相关的尿肽产生影响这一假说。在这项事后探索性分析中，我们研究了40例无并发症的1型糖尿病（T1D）患者在接受恩格列净治疗8周前后的尿样，以寻找治疗后尿肽的显著变化。我们进一步在一个独立队列中评估了这些变化与CKD的关联，以及与先前建立的名为CKD273的尿蛋白质组学面板的关联。治疗后107种个体肽有显著变化。与CKD患者和对照组相比，恩格列净诱导的大多数变化朝着“无CKD”的方向发展。与CKD患者相比，由这107种肽组成的分类器在对照组中的得分有显著差异。然而，恩格列净并未影响CKD273分类器。我们的数据表明，恩格列净可诱导尿蛋白质组学标志物如粘蛋白和簇集素发生多种显著变化。恩格列净诱导的蛋白质组学变化与临床结局之间的关系值得进一步研究。
