Effects of sodium-glucose transporter 2 inhibitors in patients with lupus nephritis: a before-and-after retrospective cohort study

Abstract Objectives The effects of sodium-glucose transporter 2 inhibitors (SGTL2i) in patients with lupus nephritis (LN) remain poorly studied. This study aimed to assess the SGLT2i effects in patients with LN and residual proteinuria through a retrospective before-and-after study. Methods We included patients with LN and residual proteinuria under maintenance treatment. Proteinuria, estimated glomerular filtration rate (eGFR), haemoglobin, hematocrit, albumin, anti-double-stranded DNA antibodies, and serum complements were registered quarterly 12 months before and after SGLT2 initiation. The trajectory of each parameter was evaluated by linear mixed models for repeated measurements. Patients were classified as “responders” if proteinuria decreased by ≥ 30% after SGLT2i. Results We evaluated 53 patients, median age of 35 years (IQR 28–46), 45 (85%) female. At SGLT2i initiation, the median proteinuria was 1.7 g/g (IQR 1.0–3.0), eGFR 94 ml/min/1.73m2 (IQR 53–114), and haemoglobin 13.4 g/dl (IQR 12.4–14.4). After initiating SGLT2i, there was a 37.6% reduction in proteinuria (95%CI -6.8% to -76.3%) in the full cohort. Thirty-two (60%) patients were responders and 21 (40%) non-responders. Before SGLT2i, the annualized eGFR slope was -6.3 ml/min/1.73m2 (95%CI -5.7to-6.9), and -2.9 ml/min/1.73m2 (95%CI -2.7to-3.1) after SGLT2i initiation (p 0.001). The effect on eGFR was observed in responders and non-responders. The median haemoglobin and hematocrit increased by 0.78 g/dl (95%CI 0.76–0.81) and 2.33% (95%CI 2.24–2.41), respectively. Six (12%) adverse events were recorded, 3 (6%) events led to emergency room evaluation or hospitalization. Conclusions In lupus nephritis the use of SGLT2i was associated with decreases in proteinuria. Beneficial changes in eGFR, haemoglobin, and hematocrit trajectories after SGLT2i initiation were observed, independent of the proteinuria response.