Assessment of Safety and Efficacy of SGLT2is Among LN Patients

Overview

The aim of this study is to assess the safety and efficacy of SGLT2is among LN patients.

SLE is a chronic debilitating autoimmune disorder that involves multiple organ systems either simultaneously or sequentially with relapsing and remitting course. The word 'Lupus' is a Latin term which means wolf. Lupus nephritis (LN) is one of the common complications in patients with SLE and influences overall outcome of these patients. About two-thirds of patients with SLE have renal disease at some stage which is a leading cause of mortality in these patients. Manifestations of LN vary from asymptomatic urinary abnormalities to rapidly progressive crescentic glomerulonephritis to end-stage renal disease (ESRD). Recently, metabolic modulation approach has become a hot spot in the management of SLE. Increased glucose metabolism in immune cells has been reported in patients with SLE. Repurposing metformin, an old anti diabetic drug, has the potential to reduce the risk of lupus flare in randomized controlled trials. A recent crossover study implied that peroxisome proliferator-activated receptor-gamma agonists might decrease cardiovascular risk in patients with SLE. Dapagliflozin, SGLT2i, is a new therapy for type 2 diabetes. The Dapagliflozin mode of action is to reduce glucose reabsorption in the epithelial cells of the proximal renal tubule of the kidney, which results in decreased blood glucose and glycated hemoglobin levels. Strikingly, four cardiovascular outcome trials demonstrated that treatment with SGLT2is (empagliflozin, canagliflozin and dapagliflozin) in patients with type 2 diabetes had prominent effects on slowing the decline rate of eGFR and decreasing albuminuria, as well as a significant reduction in cardiovascular events. Furthermore, the nephroprotective efficacy of SGLT2is was extended to non-diabetic CKD, such as IgA nephropathy. The net gain of SGLT2 inhibition is to reduce renal workload and to modulate weight loss and blood pressure. The paradigm for CKD and congestive heart failure management has been shifted accordingly Interestingly, all researchers have reported that SGLT2is could block lipopolysaccharide-induced and NLRP3-mediated inflammatory responses and regulate macrophage polarization via interplay with mammalian target of rapamycin (mTOR) and AMP-activated protein kinase pathway thereby, SGLT2is might further contribute to reducing inflammation, modulating endothelial dysfunction and decelerating atherosclerosis which are all relevant to the pathophysiology of SLE. Here, the investigators initiated this study aiming to assess the safety and efficacy of dapagliflozin among patients with LN.

Conditions

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Eligibility

Locations (1)

Outcomes

Central Contacts