Empagliflozin Therapy in Autosomal Dominant Polycystic Kidney Disease: A Feasibility Randomized Controlled Trial

Empagliflozin 25 mg once daily for 12 months was safe and well tolerated in adults with autosomal dominant polycystic kidney disease at high risk of rapid progression. Those randomized to empagliflozin had a greater rate of increase in total kidney volume over 12 months compared with placebo. There was no difference between groups in the chronic rate of change in eGFR, nor in change in vascular stiffness, symptoms, and copeptin.

Sodium-glucose cotransporter 2 inhibitors reduce the risk of diabetic and nondiabetic kidney disease progression; however, their safety and efficacy in patients with autosomal dominant polycystic kidney disease (ADPKD) are undetermined.

In this pilot and feasibility randomized controlled trial, we assigned 50 participants, 18-55 years of age, with ADPKD, at high risk of progression, not treated with tolvaptan, to receive empagliflozin (25 mg once daily) or placebo in a 1:1 ratio for 12 months. Primary outcomes were medication safety and tolerability. Secondary outcomes were (1) change in height-adjusted total kidney volume; (2) acute and chronic slope of eGFR; and (3) changes in aortic pulse wave velocity, plasma copeptin levels, urine kidney injury molecule-1, and patient-reported outcomes.

Mean age was 42±7 years, and eGFR was 70±17 ml/min per 1.73 m2. Frequency of adverse events was similar between the 2 groups. Urinary tract infection occurred in 2 empagliflozin-treated patients versus none in placebo and AKI in 1 placebo-treated patient. In total, 96% of the participants in each group tolerated the full dose of the study drug. Among the secondary outcomes, rate of change in height-adjusted total kidney volume was significantly greater in empagliflozin-treated participants (10.5%/yr; 95% confidence interval, 8.2% to 12.7%) compared with placebo (5.1%/yr; 95% confidence interval, 3.0% to 7.3%; P = 0.001). There was a faster acute decline in eGFR at 1 month among the empagliflozin (-6.2 ml/min per 1.73 m2) versus placebo groups (0.1 ml/min per 1.73 m2; P = 0.01), but no differences in eGFR change from 1 to 12 months (empagliflozin group: -0.77±1.44 ml/min per 1.73 m2 per year versus placebo group: -2.87±1.96 ml/min per 1.73 m2 per year; P = 0.4). No between-group differences were observed in changes in aortic pulse wave velocity, copeptin, urine kidney injury molecule-1, and ADPKD Impact Score.

Empagliflozin at 25 mg once daily was well tolerated by patients with ADPKD. Empagliflozin induced an expected acute decline in eGFR by 1 month, followed by stable eGFR. However, those treated with empagliflozin had a greater increase in kidney volume.

ClinicalTrials.gov, NCT05510115.