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- W4376614389 abstract "Clinical trials with sodium-glucose co-transporter 2 (SGLT2) inhibitors showed that these drugs exert kidney and cardioprotective properties, independent of glycaemic control. However, the precise mechanisms for kidney protection are not fully understood but likely include changes in inflammatory markers and fluid status. Therefore, we aimed to investigate several biomarkers of inflammation and fluid status to get a better understanding in the precise mechanism. Additionally, we aimed to investigate the effects of SGTL2 inhibitors on these biomarkers and whether these biomarkers predicted clinical outcomes. Subsequently, we assessed whether some of these markers could be used as pharmacodynamic marker of response to SGLT2 inhibition. In this thesis we showed that baseline inflammatory markers plasma tumour necrosis factor receptor (TNFR)-1, TNFR 2, kidney injury molecule (KIM-1), growth-differentiation factor (GDF)-15 and interleukin (IL)-6, and urinary epidermal growth factor (EGF) were associated with kidney or cardiovascular outcomes. We also showed that SGLT2 inhibition decreased KIM-1, increased EGF and attenuated increases in TNFR-1, TNFR-2 and IL-6. Subsequently we showed that early changes in TNFR-1, TNFR-2 and EGF were associated with a decreased risk of subsequent kidney outcomes, suggesting that these markers may be used as pharmacodynamic marker of response to SGLT2 inhibition in patients with type 2 diabetes. Finally, we demonstrated that SGLT2 inhibition activated kidney-specific adaptive mechanisms to maintain body fluid and sodium balance to prevent volume depletion including activation of the renin-angiotensin-aldosterone system and stimulation of antidiuretic hormone release in patients with chronic kidney disease without diabetes." @default.
- W4376614389 created "2023-05-17" @default.
- W4376614389 creator A5065429034 @default.
- W4376614389 date "2023-05-15" @default.
- W4376614389 modified "2023-09-24" @default.
- W4376614389 title "Mechanisms of SGLT2 inhibition in the kidney" @default.
- W4376614389 doi "https://doi.org/10.33612/diss.659987622" @default.
- W4376614389 hasPublicationYear "2023" @default.
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