Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects

FSGS and diabetic nephropathy may have common pathogenic mechanisms, that are mediated by intraglomerular hypertension, leading to hyperfiltration and proteinuria. Given that SGLT2i corrects early hemodynamic abnormalities in patients with diabetes, our aim is to determine if a similar benefit may extend to patients with FSGS. Based on previous experimental and clinical data, we hypothesize that SGLT2i will improve renal hemodynamic abnormalities characteristic of FSGS that promote renal injury and proteinuria.

Inclusion criteria

• Male or female subjects diagnosed with FSGS ≥1 month prior to informed consent
• eGFR≥45 ml/min/1.73m2
• Age 18 years or greater
• No history of diabetes
• Body Mass Index (BMI) 18.5 - 45.0 kg/ m2
• Blood pressure ≥ 100/60 at screening
• Stable therapy with either an ACEi or angiotensin II receptor blocker or direct renin inhibitor for > 1 month
• >30 mg/day and <6 g/day of proteinuria unless the patient is not a candidate for immunosuppressive therapy

Exclusion criteria

• Leukocyte and/or nitrite positive urinalysis that is untreated;
• History of organ transplantation, cancer, liver disease;
• Bariatric surgery or other gastrointestinal surgeries that induce chronic malabsorption within the past two years;
• Current treatment with systemic corticosteroids, calcineurin inhibitors, or other immunosuppressant medications;
• Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells;
• Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practising an acceptable method of birth control;
• Participation in another therapeutic trial with an investigational drug within 30 days prior to informed consent;
• Alcohol or drug abuse within three months prior to informed consent that would interfere with trial participation or any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement;
• Liver disease, defined by serum levels of alanine transaminase, aspartate transaminase, or alkaline phosphatase >3 x upper limit of normal as determined during screening;
• Cardiac, lung or peripheral vascular disease or stroke;
• Pancreas, pancreatic islet cells or renal transplant recipient;
• Medical history of cancer or treatment for cancer in the last five years prior to screening;
• History of allergy or angioedema with RAAS inhibitor exposure;
• Kidney disease due primarily to another condition aside from FSGS;