Supplementary Material for: Feasibility study of empagliflozin in patients with autosomal dominant polycystic kidney disease: Design and baseline characteristics.

Introduction Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to slow progressive loss of kidney function in both diabetic and non-diabetic proteinuric kidney diseases. Despite the benefits of SGLT2i in patients with chronic kidney disease (CKD), the potential benefits of SGLT2i in autosomal dominant polycystic kidney disease (ADPKD) have not been assessed. Methods This is a randomized, placebo-controlled trial with empagliflozin (Jardiance®) with 1-year duration and 2 participating centers including the University of Colorado Anschutz Medical Campus and the University of Maryland Medical Center. Fifty non-diabetic ADPKD patients aged 18-55 years, and estimated glomerular filtration rate of 30-90 ml/min/1.73m2 are randomized in 1:1 ratio to receive 10 mg/day empagliflozin or matching placebo. After 1 month the dose is increased to 25 mg/day empagliflozin/placebo in all patients tolerating the lower dose. Results (Outcomes) The primary outcomes are safety and tolerability of empagliflozin, the latter determined by the percentage of patients tolerating the 25 mg dose of study drug/placebo at the end of the 12-month period. Safety is assessed by the frequency of all adverse events (AE) and of specific AEs including acute kidney injury compared to placebo. Secondary outcomes include changes in total kidney volume, kidney function, aortic stiffness, copeptin level, urinary KIM-1, and PKD-specific Health Related Quality of Life questionnaire. Conclusions The outcomes of this pilot trial will provide important data regarding the safety and tolerability of empagliflozin in patients with ADPKD. Preliminary insight into the potential kidney and vascular benefits of SGLT2i will aid the design of future large scale efficacy studies.