Dapagliflozin is the first SGLT2 inhibitor to be approved for CKD treatment regardless of diabetes status. Since many etiologies of non-diabetic nephropathy are characterized by intraglomerular hypertension, it was hypothesized that dapagliflozin acutely decreases GFR and proteinuria in patients without diabetes at risk of progressive kidney function loss such as nephrotic patients via a glucose independent hemodynamic mechanism.

The aim of the study is to assess the effect of Dapagliflozin on proteinuria and estimated glomerular filtration rate in non-diabetic patients with nephrotic syndrome in order to slow the decline in kidney function and the progression to ESRD and to prevent the complications of nephrotic syndrome like thrombotic diseases, peritonitis, hyperuricemia, and recurrent infections.

Nephrotic syndrome (NS) is a clinical syndrome defined by massive proteinuria (greater than 40 mg/m2 per hour) responsible for hypoalbuminemia (less than 30 g/L), with resulting hyperlipidemia, edema, and other complications as thrombotic diseases, peritonitis and recurrent infections.

Dapagliflozin is the first SGLT2 inhibitor to be approved for CKD treatment regardless of diabetes status. Since many etiologies of non-diabetic nephropathy are characterized by intra-glomerular hypertension, it was hypothesized that Dapagliflozin decreases GFR and proteinuria in patients without diabetes at risk of progressive kidney function loss via a glucose independent hemodynamic mechanism.

The aim of the study is to assess the effect of Dapagliflozin on proteinuria and estimated glomerular filtration rate in non-diabetic patients with nephrotic syndrome.

The study will include 90 patients with diagnosis of nephrotic syndrome (proteinuria ≥3.5g/24hr, and serum albumin ≤30g/L) and Urine protein/Creatinine Ratio (UPCR) ≥2. Serum creatinine <3mg/dl (265.2umol/L) and eGFR >30 ml/min/1.73 m2. They will assigned randomly into 2 groups. Each group will contain 45 patients.

• The first group will receive Dapagliflozin (Diglifloz) 10 mg orally once daily for 24 weeks and the standard therapy (ACEI or ARB).
• The second group will receive the standard therapy (ACEI or ARB).

A. Baseline assessment:

At baseline , the non-diabetic patients with nephrotic syndrome will undergo:

• A detailed medical history,
• Physical examination,
• Blood pressure,
• Complete blood count (CBC),
• Baseline biochemical laboratory tests including: kidney function tests (Urinary protein/creatinine ratio (UPCR), eGFR, serum albumin, serum creatinine, serum uric acid, Blood urea nitrogen (BUN), lipid profile and serum glucose level

B. Follow up assessment:

Patients will be followed up every four weeks during the study period (6 months) by measuring UPCR, eGFR, serum albumin, serum creatinine, Blood urea nitrogen (BUN), blood pressure, uric acid, glucose level, lipid profile and CBC. In between visits, patients will be contacted via phone for monitoring of any side effects.

C. End of study assessment:

After 6 months, the previous biochemical tests will be performed such as UPCR, eGFR, serum albumin, serum creatinine, Blood urea nitrogen (BUN), blood pressure, uric acid, glucose level, lipid profile and CBC to measure changes from the baseline.

Inclusion Criteria:

• Age ≥18 and ≤60 years.
• Patients with diagnosis of nephrotic syndrome (proteinuria ≥3.5g/24hr, and serum albumin ≤30g/L) and Urine protein/Creatinine Ratio (UPCR) ≥2.
• Serum creatinine <3mg/dl (265.2umol/L) and eGFR >30 ml/min/1.73 m2.
• Pathological diagnosis with membranous nephropathy (MN) or focal segmental glomerulosclerosis (FSGS).
• Absence of any contraindication to dapagliflozin (eGFR less than 30).
• On a stable dose of an ACEI or ARB for at least 4 weeks prior to randomization or Initiation of ACEI or ARB.
• Agreed to participate and sign written informed consent.

Exclusion Criteria:

• Diagnosis of type 1 or type 2 diabetes mellitus.
• Autosomal dominant polycystic kidney disease or autosomal recessive polycystic kidney disease or lupus nephritis.
• Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.
• History of severe hypersensitivity or contraindications to dapagliflozin.
• History of repeated urinary tract infection or fungal infection.
• Patients with Hemodynamic instability or Hypotension.
• History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
• Pregnancy or breastfeeding.

90 opaque envelopes will be numbered serially and the corresponding letter which denotes the allocation will be put according to the electronic randomization table. Then all envelopes will be closed and put in one box. When the first patient arrives, the envelope will be opened and the patient will be allocated according to the letter inside.