Background
Chronic kidney disease (CKD) is the condition where the kidneys are unable to filter and clean the blood of waste properly. Hypertension, obesity, and diabetes are the leading risk factors for developing CKD. Fibrosis is regarded as a final common pathway leading to CKD. Sodium‐glucose co‐transporter 2 (SGLT‐2) inhibitors have shown to be renoprotective in type 2 diabetes patients. However, the mechanisms that underlie the renoprotective effects of SGLT‐2 inhibitors are unclear. Our study investigated whether empagliflozin (an SGLT‐2 inhibitor) treatment inhibits transforming growth factor β (TGF‐β)‐mediated fibrosis and profibrotic signaling in rat renal proximal tubular cells (NRK‐52E).
Methods
NRK‐52E cells were cultured and treated with TGF‐β with or without empagliflozin for 24 and 48 hours. The expression of fibrosis markers ‐ alpha‐smooth muscle actin (α‐SMA) and vimentin, autophagy marker – LC3II, and TGF‐b‐mediated profibrotic signaling marker ‐ SMAD 2 – were measured by western blotting.
Results
TGF‐β treatment (at 5 ng/mL and 10 ng/mL) for 24 and 48 hours induced fibrosis and activated autophagy signaling in renal proximal tubular cells. For instance, 48 h TGF‐β treatment at 10 ng/mL induced the expression of α‐SMA by 1.43‐fold and LC3II by 2.6‐fold as compared to vehicle‐treated cells. Co‐treatment with empagliflozin (100 and 500 nM) reduced the expression of the fibrotic markers (α‐SMA, vimentin), autophagy marker (LC3II) and TGF‐β‐mediated phosphorylation of SMAD‐2 in renal proximal tubular cells.
Conclusions
Our preliminary findings indicate that TGF‐β‐mediated induction of fibrosis, autophagy, and profibrotic signaling could be attenuated by empagliflozin treatment. Further studies are required to understand the molecular mechanisms that underpin the antifibrotic effects of empagliflozin against TGF‐β‐induced renal fibrosis.
III. Conclusion.Often the goal in acute illness is aggressive treatment or extensive diagnostic evaluation and palliative care goals may be perceived as conflicting. This case report illustrates the poor outcomes that can result if goals of care are not clearly elucidated but also an opportunity to upstream palliative care.
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