Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis:a prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial

Background Despite renin-angiotensin-aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy. Methods In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m(2) and urinary albumin:creatinine ratio (UACR) 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10 mg once daily or placebo as an adjunct to standard care and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline >= 50%, end-stage kidney disease, or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment). Results Of 104 participants with biopsy-confirmed FSGS, 45 were randomized to dapagliflozin and 59 to placebo. Mean (standard deviation) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73 m(2) and median (interquartile range) UACR 1248 (749-2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomized to dapagliflozin and placebo, respectively [hazard ratio 0.62, 95% confidence interval (95% CI) 0.17, 2.17]. Dapagliflozin led to a larger acute reduction (standard error) in eGFR compared with placebo (-4.5, 95% CI -5.9 to -3.1 versus -0.9, -2.1 to 0.4 mL/min/1.73 m(2)/2 weeks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were -1.9 (-3.0, -0.9) and -4.0 (-4.9, -3.0) mL/min/1.73 m(2)/year, respectively (difference 2.0, 95% CI 0.6 to 3.5, mL/min/1.73 m(2)/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events