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.