Dapagliflozin in Inactive Lupus Nephritis: Preliminary Results of a Cross-Over Trial

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD). Lupus nephritis (LN) patients were excluded from the main trials with SGLT2 inhibitors. This trial aims to assess the effect and safety of dapagliflozin in inactive LN patients with residual proteinuria. Methods: For this cross-over randomized trial, we include adult patients with LN class III, IV (+/-V) without active nephritis but with proteinuria >500mg/24h and ≥ 20ml/min, in the maintenance treatment with a RAAS and MMF<2g/day in stable a dose for at least 4 weeks. We excluded patients with other etiologies of CKD, those with active LN lesions on the recent biopsy (AI>2), use of induction therapy in the last 12 mo. Those included were randomized to receive dapagliflozin 10mg on top of standard of care therapy (SoC) or not. After 24 weeks the groups were switched and those without dapagliflozin received it for the next 24 weeks. Primary endpoint is reduction of proteinuria compared to baseline at 6 and 12 mo. The sample size was calculated for 28 patients enrolled providing 80% power to detect a 25% relative risk reduction in proteinuria (α 0.05). Results: From 97 screened class III, IV (+/- V) LN patients, we excluded 67 due to active LN, low proteinuria or low eGFR. We included 30 patients that were randomized 14 to start the treatment with dapagliflozin on top of SoC and 16 to remain with the usual therapy for 24 weeks. Eight patients were excluded from the analysis due to new LN flare or lost to f/u. We analyzed the data of 10 patients in the initial dapa+SoC and 12 patients in the initial SoC group after 3 (n=21), 6 (n=21), 9 (n=19) and 12 (n=17) mo. Patients in initial dapa group had a significant decrease in proteinuria after 6 months (1018 to 609mg/day; p=0.017) but increased to 1060mg/day 6 months after the drug withdrawal. This preliminary analysis shows a significant reduction in the proteinuria of –37.3% (+/-38) in patients after 6mo of dapagliflozin as opposed to a 0% (+/-54) for those in the SoC therapy at the end of a 6mo period, p=0.026. Conclusion: Preliminary results show a significant reduction in residual proteinuria in patients with inactive LN with dapagliflozin without an increase in infections. Funding: Government Support – Non-U.S.