Abstract
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.
Highlights
Diabetes-associated vascular diseases, especially chronic kidney disease (CKD) represent a major burden for developed societies [1]
No consistent impact of the empagliflozin treatment on CKD273 could be observed in this cohort. In this analysis we investigated the impact of empagliflozin treatment on the urine proteome in type I diabetes patients with preserved kidney function
In several recent studies urinary proteomic changes were reported as a consequence of therapeutic intervention, both based on drugs [13,23], and on diet or lifestyle [24,25]
Summary
Diabetes-associated vascular diseases, especially chronic kidney disease (CKD) represent a major burden for developed societies [1]. Treatment of CKD in diabetes, referred to as diabetic kidney disease, DKD, is typically initiated when first symptoms are evident: persistent microalbuminuria or decreased glomerular filtration rate (GFR). Standard treatment is reduction of blood pressure by interfering with the rennin/angiotension/aldosterone systems (RAAS). SGLT2 inhibition may represent an additional renoprotective intervention–beyond the use of renin angiotensin aldosterone system blockade–for DKD. Multiple recent reports have demonstrated the potential of proteomic biomarkers in kidney disease, as reviewed in [4].
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