Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: A prespecified analysis of the DAPA-CKD trial.

2021 
Background Despite renin-angiotensin-aldosterone-system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this pre-specified analysis of DAPA-CKD was to assess efficacy and safety of dapagliflozin in a small subgroup participants with FSGS confirmed by kidney biopsy. Methods In DAPA-CKD, patients with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g (22.6-565 mg/mol) were randomised to dapagliflozin 10mg 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 (ESKD), 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 randomised to dapagliflozin and 59 to placebo. Mean (SD) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73m2 and median (IQR) UACR 1248 (749-2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomised to dapagliflozin and placebo, respectively (HR 0.62, 95%CI 0.17-2.17). Dapagliflozin led to a larger acute reduction (SE) in eGFR compared to placebo (-4.5 [95% CI - 5.9--3.1] vs - 0.9 [-2.1-0.4] mL/min/1.73m2 per 2 wks). 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/1.73m2/year, respectively (difference 2.0 [95%CI 0.6-3.5] mL/min/1.73m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin. Conclusion Among DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared to placebo, although this difference was not statistically significant.
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