Dapagliflozin in Active Lupus Nephritis

This is a pilot and feasibility randomized, double-blind, placebo-controlled trial involving patients with active lupus nephritis. It will be a concealed allocation, blinded randomized controlled trial of dapagliflozin 10 mg/day or matched placebo in a 2:1 allocation ratio (22 subjects active arm: 11 subjects placebo arm), in addition to standard-of-care treatment, for 12 weeks. After informed consent, 33 eligible subjects will be randomized 2:1 to oral dapagliflozin 10 mg/day or identical oral placebo/day for 12 weeks. Study visits will occur at screening (Visit -1), baseline (Visit 0) and weeks 4 (Visit 1), 8 (Visit 2) and 12 (Visit 3). Observational data including laboratory test results obtained in routine clinical care will be collected through 12 months of follow-up.

The primary outcomes are:

• the overall proportion of identified as potentially eligible/pre-screened patients who enroll in the trial;
• feasibility and completeness of data collection procedures;
• changes in urine protein-to-creatinine ratio (UPCR) and precision of these estimates from baseline to week 12 in each group; and
• rates and proportions of serious adverse events and of adverse events of interest, including genitourinary infections and volume depletion.

Inclusion criteria

• • Age 18-70 years, fulfilling 2012 SLICC or 2019 ACR/EULAR criteria for SLE, with biopsy-proven class III, IV and/or V LN

• Active (new or relapsing) LN within the prior six months, with at least one of the following:

• Kidney biopsy with activity index >2 and/or
• Active urinary sediment (>5 RBCs, >5 WBCs, or cellular casts)
• Receiving standard-of-care immunosuppression regimen for active LN, including mycophenolate, cyclophosphamide, belimumab, azathioprine, a calcineurin inhibitor, and/or B cell depleting therapies
• Recent or ongoing glucocorticoids use for active LN within the past 6 months
• Receiving standard-of-care antimalarial therapy and RAAS blockade, unless contraindicated
• Estimated ≥0.5 g/g 24 hr proteinuria or ≥0.3 mg/g 24 hr microalbuminuria at enrollment (on first morning urine)
• Ability to given informed consent

Exclusion criteria

• GFR < 25 ml/min/1.73m2

• Acute kidney injury at study enrollment (>50 percent rise in creatinine within 90 days)
• Type I diabetes, underweight (BMI <18.5), active malignancy, active infection, or recurrent genitourinary infections
• For females: pregnancy, or desiring of pregnancy and not using contraception, or unable to use contraception
• Current use of >1mg/kg/day prednisone equivalent
• Current or prior use of SGLT2 inhibitors or GLP-1 receptor agonists