#5217 PROTOCOL AND PRELIMINARY RESULTS OF DAPAGLIFLOZIN IN INACTIVE LUPUS NEPHRITIS CROSS-OVER RANDOMIZED TRIAL

Abstract Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) with and without type 2 diabetes. Lupus nephritis (LN) patients under immunosuppression were excluded from the most important trials with SGLT2 inhibitors. Thus, efficacy and tolerance of these drugs are unknown in such patients. The present trial will assess the effect of Dapagliflozin in patients with inactive Lupus Nephritis with residual proteinuria. Method For this cross-over randomized trial, we will include adult patients with LN class III, IV (+/-V) without active nephritis but with proteinuria > 500mg/24h or UPC > 200mg/g and eGFR ≥ 20ml/min, in the maintenance treatment. RAAS inhibition should be stable for at least four weeks before the randomization. We will exclude 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 >2 g/day and Calcineurin inhibitors) and prednisone dose ≥ 20 mg/day. Due to safety issues, we will exclude patients with recurrent urinary infections (>3 times/year). They will be randomized to receive Dapagliflozin 10mg on top of standard of care therapy or not. After 24 weeks the groups will be switched and those without Dapagliflozin will receive it for the next 24 weeks. Primary endpoint will be reduction of proteinuria compared to baseline at 6 and 12 months. Secondary endpoints will include sustained reduction of eGFR > 30%; changes in weight and blood pressure compared to baseline; and number of infections on Dapagliflozin treatment versus exclusive standard of care 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 85 screened class III, IV (+/- V) LN patients under maintenance therapy, we excluded 65 due to active nephritis, low proteinuria or low eGFR. Until now we included 17 patients that were randomized 1:1 to start the treatment with Dapagliflozin on top of standard care or remain with the usual therapy for 24 weeks. Patients’ baseline characteristics are described in Table 1. All patients randomized were using Mycophenolate Mofetil ≤2 g/day and RAAS inhibition and 14 of them were receiving Hydroxychloroquine. Conclusion We expect that the present trial will determine whether the SGLT2 inhibitor Dapagliflozin, added to LN maintenance therapy, could safely reduce the residual proteinuria of inactive LN patients.