#2817 Preliminary results of dapagliflozin in inactive lupus nephritis cross-over randomized trial

Abstract

Abstract Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD). Lupus nephritis (LN) patients in remission may continue with residual proteinuria due to scars and hyperfiltration. However, 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. Method For this cross-over randomized trial, we include adult patients with LN class III, IV (±V) without active nephritis but with proteinuria >500 mg/24 h or UPC > 200 mg/g and eGFR ≥ 20 ml/min, in the maintenance treatment with a RAAS and mycophenolate mofetil (<2g/day) in stable a dose for at least four weeks before the randomization. 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 months (cyclophosphamide, mycophenolate mofetil >2g/day and calcineurin inhibitors) and prednisone dose ≥ 20 mg/day. Due to safety issues, we excluded patients with recurrent urinary infections (>3 times/year). Those included were randomized to receive dapagliflozin 10 mg 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 months. Secondary endpoints are sustained reduction of eGFR>30%; occurrence of hypotension symptoms; and number of infections on dapagliflozin treatment versus exclusive SoC therapy. The sample size was calculated for 28 patients enrolled providing 80% power to detect a 25% relative risk reduction in proteinuria (α level of 0.05). Results From 97 screened class III, IV (± V) LN patients under maintenance therapy, we excluded 67 due to active nephritis, 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. Six patients were excluded from the analysis due to new LN flare or lost to follow-up. We analyzed the data of 12 patients in the initial Dapa + SoC and 12 patients in the initial SoC group after 3 (n = 21), 6 (n = 18), 9 (n = 14) and 12 (n = 12) months. Patients in initial Dapa group had a significant decrease in proteinuria after 6 months (1159 to 882 mg/day; p = 0.017) but increased to 1105 mg/day 6 months after the drug withdrawal (Fig. 1A). This preliminary analysis shows a significant reduction in the proteinuria of –35.8% in patients after 6 mo of dapagliflozin as opposed to an increase in 7.2% for those in the SoC therapy at the end of a 6 mo period, p = 0.02 (Fig. 1C). The drug was well tolerated, but 4 (33.3%) of the patients reported hypotension symptoms during the first days of dapagliflozin. There was one case of urinary infection in each group, but in the same patient. Conclusion Preliminary results show a significant reduction in residual proteinuria in patients with inactive LN with dapagliflozin without an increase in infections.