AB1061 EFFECTIVENESS OF DAPAGLIFOZIN IN REDUCING PROTEINURIA IN PATIENTS WITH MEMBRANOUS LUPUS NEPHROPATHY
Authors: L. D. Fajardo Hermosillo, M. K. L. López Ramírez
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Lupus nephopathy (LN) occurs in more than half of patients with systemic lupus erythematosus (SLE). Despite current treatment, 40% of patients progress to kidney failure requiring replacement treatment and kidney transplant, increasing the costs of their care and precarious their quality of life [1]. The persistence of 24-hour urine protein (24hUP) &gt; 700 mg/day at 8 months is a risk factor for the progression of renal deterioration [2]. Currently, the management of proteinuria in these patients is an unmet need; the use of immunosuppressants, corticosteroids, a diet &lt; 100 grams of protein daily, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are not effective in 40% of the cases [1]. Dapaglifozin (DAPA), a sodium-glucose cotransporter-2 inhibitor, has been identified to have renal/cardiac protective effects in different diseases. In SLE, DAPA significantly decreased proteinuria in murine models and shown a renoprotective effect in a small clinical trial [3, 4]. Could DAPA use in membranous lupus nephropathy (MLN) reduce 24hUP? <h3>Objectives:</h3> This study compares the effectiveness of DAPA in reducing 24hUP and achieving a complete (CR) or partial remission (PR) in patients with MLN over 6 months of follow-up. <h3>Methods:</h3> Mexican patients with SLE classified according to the SLICC 2012 criteria from 2021 to 2023 with MLN diagnosed by renal biopsy were recruited. Demographic, renal clinical and paraclinical variables were examined. All patients received oral prednisone (1 mg/kg/day) accompanied by tacrolimus (TAC) 6 mg/day and only the experimental group received DAPA 10 mg/day. CR was defined as normal serum creatinine (sCr), inactive urinary sediment, plus 24hUP &lt;500 mg/day and PR was established as a 50 percent improvement in renal parameters. 24hUP, CR and PR were evaluated at 0, 3 and 6 month(s) after the start both treatments. For the bivariate analysis, Fisher's exact and Mann-Whitney U tests were employed. Kaplan-Meier survival analysis was used to assess CR and PR. <h3>Results:</h3> Of 26 SLE patients with MLN, five were men. The mean age [standard deviation (SD)] was 38.6 (10.1) years. The mean time at the onset of SLE (SD) was 5.1 (1.8) years ago. The mean baseline SLEDAI (SD) were 6.08 (2.08). The median baseline 24hUP [interquartile range (IQR 25-75)] was 1.73 (1.41-3.66) g/day and median of sCr (IQR) was 0.95 (0.7-1.5) mg/dl. Thirteen patients used TAC+DAPA and 13 patients utilized TAC alone. No statistically significant differences were found for 24hUP between both groups during follow-up (Table 1). At 3 months, two patients in both groups achieved a CR (p=1.000), while four patients with TAC+DAPA and seven patients with TAC reached a PR (p=0.428). At 6 months, four patients with TAC+DAPA and nine patients with TAC achieved a CR (p=0.115), while eight patients with TAC+DAPA and eleven with TAC had a PR (p=0.378). Furthermore, the Kaplan-Meier survival analysis for CR and PR found no differences between both groups (Figure 1). Finally, we did not observe adverse effects as infections and hypoglycemia in the DAPA group. <h3>Conclusion:</h3> This study found no statistically significant differences in the reduction of proteinuria or the achievement of CR and PR between patients with MLN treated with DAPA for six months. However, these observations need to be confirmed in larger prospective studies. <h3>REFERENCES:</h3> [1] Fanouriakis A et al. Ann Rheum Dis 2020;79(6):713-723. [2] Tamirou F et al. Lupus Science &amp; Medicine 2015;2:e000123. [3] Zhao X et al. Ann Rheum Dis 2023:ard-2023-224242. [4] Wang H et al. RMD Open 2022;8(2):e002686. <h3>Acknowledgements:</h3> All members of rheumatology department, UMAE-HE, CMNO, IMSS. <h3>Disclosure of Interests:</h3> <b>None declared.</b>