Pos1026 Analyzing Renal and Cardiovascular Outcomes in Lupus Nephritis: A Comprehensive Cohort Studying the Use of SGLT-2 Inhibitors in Systemic Lupus Erythematosus

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder with frequent renal involvement. Approximately 10%–30% of patients with Lupus Nephritis (LN) may progress to end-stage renal disease (ESRD) within 15-years. Cardiovascular(CV) events are increased in patients with SLE, a major contributor to mortality. The distinct cardiorenal protective effects exhibited by Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) in Chronic Kidney Disease (CKD) patients present an appealing therapeutic opportunity for the management of SLE/LN. Objectives: To observe and compare renal and CV outcomes in LN patients treated with SGLTi versus those that were treated with Hydroxychloroquine (HCQ) and Mycophenolate Mofetil (MMF) The aim of our study is to contribute valuable insight into potential therapeutic benefits of SGLTi in the context of LN. Methods: An observational retrospective cohort study was conducted involving patients 18 years and older diagnosed with Lupus Nephritis (defined by International Classification of Diseases, Tenth Revision (ICD-10 codes). TrinetX database was utilized which includes electronic health care records from >80 different global health care organizations. Two cohorts were created: individuals with LN on HCQ and MMF+ utilizing SGLT inhibitors (specifically Dapaglifozin, Empaglifozin, and Canaglifozin), while excluding those who received Azathioprine, Methotrexate, Belimumab, or Anifrolumab (confirmed via RxNorm codes). Cohort 2: matched cohort 1 as above, excluding patients on SGLT-2i. Propensity score matching was employed for baseline characteristics, and the following preexisting conditions: hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, and heart failure. The primary outcomes were assessed within a 3-year timeframe after initiation of SGLT-2 inhibitors. Outcomes included ESRD (patients with ESRD prior to initiation of SGLTi were excluded), all-cause mortality, Cerebrovascular disease, development of Chronic Kidney Disease Stage 5 (CKD5) Hypertensive CKD, Hypertensive Crisis, hypertensive heart disease, Myocardial Infarction (MI), Ischemic Heart Disease, Pulmonary Embolism, and Cardiomyopathy. Results: Our findings revealed statistically significant improvements in specific clinical outcomes among Lupus Nephritis patients using SGLT-2 inhibitors. Noteworthy results include a reduced risk of developing Cerebrovascular disease, Hazard Ratio (HR) of 0.616 (95% CI: 0.354, 1.072) p-value of 0.021. There was a reduced risk of Hypertensive Chronic Kidney Disease (CKD), Hazard Ratio of 0.773 (96% CI: 0.564, 1.060), p-value of 0.002. A lower risk of CKD5 was also noted (risk difference -.064 (-0.111, -0.017), p-value of.008). In contrast, the analysis indicated a higher Hazard Ratio for Ischemic Heart Disease (IHD) at 1.454 (95% CI: 0.986, 2.143), p-value of 0.023, signifying a potential increased risk of IHD. It's crucial to note that other investigated outcomes did not demonstrate statistically significant differences between the cohorts. Conclusion: Our study suggests that SGLT-2 inhibitors may offer potential renal and cardiovascular benefits, specifically in the development or progression of nephropathy to CKD5, hypertensive CKD, and cerebral vascular accidents. We did not find any statistically significant benefits in preventing LN from progressing to ESRD. While SGLT-2 inhibitors are deemed safe and show promise in reducing proteinuria, larger-scale, placebo-controlled trials are imperative to substantiate the safety and cardiorenal effects in LN. Acknowledgements: NIL. Disclosure of Interests: None declared.