Markers of Kidney Injury, Inflammation, and Fibrosis Associated With Ertugliflozin in Patients With CKD and Diabetes.

Abstract: Introduction Sodium glucose cotransporter-2 (SGLT2) inhibitors improve cardiovascular and kidney outcomes through mechanisms that are incompletely understood. In this exploratory post hoc analysis of the VERTIS RENAL trial, we report the association between the SGLT2 inhibitor ertugliflozin and markers of kidney injury, inflammation, and fibrosis in participants with type 2 diabetes and stage 3 chronic kidney disease. Methods Participants were randomized to ertugliflozin (5 or 15 mg/day) or placebo and plasma samples for biomarker analysis were collected at baseline, 26, and 52 weeks. Results Ertugliflozin treated participants had lower plasma levels of kidney injury molecule 1 (KIM-1) at 26 (p = 0.044) and 52 weeks (p = 0.007), and higher eotaxin-1 at 52 weeks (p = 0.007) post-randomization when compared to placebo. Change in KIM-1 was not associated with baseline albumin to creatinine ratio or estimated glomerular filtration rate (p-interaction > 0.05). Additionally, change in KIM-1 was positively correlated with change in albumin to creatinine ratio in participants treated with ertugliflozin (p = 0.0071). No other significant associations between ertugliflozin and changes in markers of tubular injury, inflammation, fibrosis, oxidative stress, and endothelial dysfunction were observed. Conclusion In conclusion, in participants with type 2 diabetes and stage 3 chronic kidney disease, ertugliflozin was associated with a sustained lowering of the tubular injury marker, KIM-1, regardless of baseline kidney function.