Efficacy and safety of dapagliflozin in inactive lupus nephritis: a randomized crossover trial

BACKGROUND: Lupus nephritis (LN) patients under immunosuppression were excluded from the main trials with sodium-glucose co-transporter 2 inhibitors. This trial aims to analyse the effect and safety of dapagliflozin in inactive LN patients with residual proteinuria. METHODS: We recruited adult LN patients (class III, IV(±V)] without activity, with proteinuria >500 mg/24 h and an estimated glomerular filtration rate (eGFR) ≥20 ml/min, on maintenance treatment with stable renin-angiotensin-aldosterone system inhibitors and mycophenolate mofetil ≤2 g/day. They were randomized to receive dapagliflozin on top of standard-of-care (SoC) therapy or not. After 6 months the groups were crossed over. The primary endpoint is a reduction of proteinuria compared with baseline (6 and 12 months). RESULTS: From 97 screened patients, we excluded 67 due to active LN, low proteinuria or low eGFR. Thirty patients were randomized: 14 to start the treatment with dapagliflozin on top of SoC therapy and 16 to remain with the usual therapy for 6 months. Nine patients were excluded from the analysis due to new LN flares or lost to follow-up. The mean age was 40.6 ± 12.3 years, 19 (90.5%) were female, none had diabetes and the mean body mass index was 26.1 ± 5.2. The final analysis showed a significant reduction in proteinuria of -36.1% in patients after 6 months of dapagliflozin as opposed to -3.5% for those in the SoC therapy group (P = .03). There were more reported hypotension symptoms in the dapagliflozin group [7 cases (33.3%)] but no drug withdrawal and no significant changes in blood pressure or weight in the follow-up between the groups. There was one case of urinary infection in each group, but in the same patient. CONCLUSIONS: We demonstrate a significant reduction in residual proteinuria in patients with inactive LN with dapagliflozin without safety concerns.