Effects of Dapagliflozin in Patients with Membranous Nephropathy

Introduction Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to end-stage kidney disease (ESKD). The objective of this prespecified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial. Methods Patients with an estimated glomerular filtration rate (eGFR) of 25–75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200–5000 mg/g were randomized to dapagliflozin 10 mg once daily or placebo, along with standard-of-care and followed for median 2.4 years. The primary endpoint was a composite of ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Exploratory efficacy endpoints included eGFR slope and UACR. Results Among DAPA-CKD participants with membranous nephropathy, 19 were randomized to dapagliflozin and 24 to placebo. Mean (SD) age was 59.9 ± 12.1 years; mean eGFR 45.7 ± 12.1 mL/min/1.73m2, and median UACR 1694.5 (25%, 75% range 891–2582.5) mg/g. Two of 19 (11%) patients randomized to dapagliflozin, and five of 24 (21%) randomized to placebo experienced the primary composite endpoint. Total and chronic mean eGFR slopes for dapagliflozin and placebo were −3.87 and −4.29 and −2.66 and −4.22 mL/min/1.73m2/year, respectively; corresponding between-group mean differences were 0.42 and 1.57 mL/min/1.73m2/year. Dapagliflozin reduced geometric mean (SEM) UACR relative to placebo (−29.3% ± 1.2% versus −3.6% ± 1.1%; between-group mean difference [95% CI] −26.7 [−50.4, 8.3]). Four (21%) patients randomized to dapagliflozin and seven (29%) randomized to placebo experienced a serious adverse event. Conclusions In membranous nephropathy, effects of dapagliflozin on kidney disease progression and albuminuria were generally favourable; there was insufficient power to justify formal inference testing.