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Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to kidney failure. The objective of this pre-specified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial.
Patients with estimated glomerular filtration rate (eGFR) 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 a median of 2.4 years. The primary endpoint was a composite of sustained decline in eGFR ≥50%, kidney failure, or kidney or cardiovascular death. Exploratory efficacy endpoints included eGFR slope and UACR.
Among DAPA-CKD participants with membranous nephropathy, 19 were randomized to dapagliflozin and 24 to placebo. Mean age was 60 ± 12 years, 27% were female, with eGFR 46 ± 12 mL/min/1.73m2, and median UACR 1695 mg/g (interquartile range [25%–75%] 891–2583 mg/g). Two of 19 (11%) patients randomized to dapagliflozin and five of 24 (21%) randomized to placebo experienced the primary composite endpoint. For dapagliflozin and placebo, respectively, total mean (SD) eGFR slope was –3.87 ± 1.38 and –4.29 ± 1.23 mL/min/1.73m2/year (between-group mean difference [95% CI] of 0.42 [–3.20, 4.03] mL/min/1.73m2/year) and total chronic slope was –2.66 ± 1.36 and –4.22 ± 1.21 mL/min/1.73m2/year (between-group mean difference [95% CI] of 1.57 [–2.00, 5.14] mL/min/1.73m2/year). Dapagliflozin reduced geometric mean UACR relative to placebo (–15.0% [95% CI –29.7, 2.8] versus –2.8% [95% CI –18.1, 15.3]). Four (21%) patients randomized to dapagliflozin and seven (29%) randomized to placebo experienced a serious adverse event.
In membranous nephropathy, effects of dapagliflozin on kidney disease progression and albuminuria were generally favorable; there was insufficient power to justify formal inference testing.