Dapagliflozin in lupus nephritis: renal and hematologic outcomes from a randomized controlled trial

Why clinicians should know about it

• Picked for Nephrology (top studies of the week, 9 August 2026): Dapagliflozin shows numerical proteinuria reduction in lupus nephritis trial
• Picked for Transplantation (top studies of the week, 9 August 2026): High-quality evidence in a top journal
• Picked for Rheumatology (top studies of the week, 9 August 2026): Recent Rheumatology research from a high-quartile journal
• Picked for Hematology (top studies of the week, 9 August 2026).
• Picked for Pathology and Forensic Medicine (top studies of the week, 9 August 2026).

Abstract

BACKGROUND: Lupus nephritis (LN) remains a major cause of chronic kidney disease (CKD) and end-stage renal disease despite advances in immunosuppressive therapy. Sodium-glucose cotransporter-2 (SGLT2) inhibitors confer renal protection in diabetic and nondiabetic CKD and have been associated with increases in hemoglobin levels, but their renal and hematologic effects in immune-mediated glomerulopathies such as LN are not well defined. OBJECTIVE: To evaluate the renal and hematologic effects, efficacy, and safety of dapagliflozin as adjunctive therapy in patients with LN. METHODS: In this randomized, double-blind, placebo-controlled trial, 79 adult patients with biopsy-proven LN and estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m2 were randomized to receive dapagliflozin 10 mg/day (n = 38) or placebo (n = 41) for 12 months in addition to standard immunosuppressive therapy. The primary renal endpoint was percentage change in 24-h urinary protein excretion. Secondary renal outcomes included change in eGFR. Hematologic parameters assessed at baseline and 12 months included hemoglobin, erythropoietin, hepcidin, ferritin, and transferrin saturation. The primary analysis used analysis of covariance (ANCOVA) with adjustment for baseline values and clinically relevant covariates including age and background immunosuppressive therapy. Sensitivity analyses using log-transformed proteinuria were also performed. Additional analyses evaluated adjusted 12-month eGFR and eGFR slope. RESULTS: At 12 months, dapagliflozin was associated with a numerical reduction in proteinuria compared with placebo; however, this difference did not reach statistical significance. Adjusted analyses using ANCOVA confirmed the absence of a significant treatment effect. No significant differences were observed in eGFR, eGFR slope, or hematologic parameters. CONCLUSION: In this randomized controlled trial, dapagliflozin was associated with a numerical reduction in proteinuria that did not reach statistical significance after adjustment for baseline characteristics and background immunosuppressive therapy. No significant effect on kidney function, eGFR slope, or hematologic parameters was observed. These findings suggest a possible signal that requires confirmation in larger, adequately powered, longer-duration studies.Clinical trials registration number: NCT05748925 (ClinicalTrials.gov). Registered 28 February 2023-Retrospectively registered (https://register.clinicaltrials.gov/prs/beta/studies/S000CWI200000138/recordSummary).

Abstract as published, via PubMed.