Kidney and Systemic Effects of SGLT2 Inhibitors in Patients with CKD Secondary to Lupus Nephritis

Background: The utility of SGLT2 inhibitors in patients with lupus nephritis (LN) remains controversial. This study aimed to evaluate kidney and systemic effects of SGLT2i in patients with CKD secondary to LN. Methods: We included LN patients on SGLT2i with: 1) use ≥12 months post-flare, 2) proteinuria ≥0.5g/gCr, 3) prednisone ≤10mg/day, 4) labs 12 months pre- and post-initiation, 5)adherence to SGLT2i, defined by the presence of glucosuria. We evaluated the course of eGFR, proteinuria, hemoglobin, hematocrit, serum albumin, anti-dsDNA, C3, C4 were analyzed via linear mixed models. Responders: ≥30% proteinuria drop post-SGLT2i. Results: We included 53 patients, 45 (85%) female, median age of 35 years (IQR 28-46). The median time from the last LN episode was 28 months (IQR 15-77). At SGLT2i initiation, the median proteinuria was 1.7g/gCr (IQR 1.0-3.0), eGFR 94ml/min/1.73m2 (IQR 53-114), and hemoglobin 13.4g/dL (IQR 12.4-14.4). In the full cohort, the geometric mean of proteinuria reduction was 49% (SEM 42-62%) after SGLT2i initiation. Based on proteinuria reduction 32 (60%) were classified as responders and 21 (40%) as non-responders. In the full cohort, annualized eGFR slope was -7.4ml/min/1.73m2 (95%CI -6.7 to -8.4) and -4.4ml/min/1.73m2 (95%CI -4.1 to -4.7) before and after SGLT2i initiation (p<0.001). The effect on eGFR was observed in both responders and non-responders. After SGLT2i initiation, the hemoglobin and hematocrit increased by 0.70g/dL (0.3 to 1.50) and 2.53% (2.43 to 2.62), respectively. There were no significant changes in serum albumin, anti-dsDNA antibodies, and complement C3/C4 after SGLT2i initiation. There were 6 (12%) adverse events, including 3 (6%) events that led to ER evaluation or hospitalization. Conclusion: In patients with LN in maintenance phase, SGLT2i initiation decreased proteinuria ≥30% in 60% of patients. There were significant changes in the eGFR, hemoglobin, and hematocrit slopes after initiation of SGLT2i.Figure. Course of proteinuria (A), eGFR (B), and hematocrit (C) 12 months before and after SGLT2i start.