This study aims to assess sodium glucose linked transoprter inhibitors(SGT2i) role in regression of ongoing kidney and cardiac diseases among lupus nephritis patient either diabetic or non-diabetic under different immunosuppressive therapy.

The main objective of this study is to:

To compare use of sodium glucose linked transoprter inhibitors (SGLT2i) versus standard care in regression of chronic kidney disease in patient with lupus nephritis (LN).

To study the safety and efficacy of this drug group with use of immunosuppression and possible interaction.

Patients with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2 will be randomized into two groups Study group will receive SGLT2i inhibitor as add on drug or replace another drug according to patient clinical situation, Dapagliflozin 10 mg and 25 mg will be used once daily with or without food.

Control group will be maintained on placebo.We will follow up all patients for 12 months and compare their results.

Study sitting:

Nephrology and renal transplant unit at urology and nephrology center in Mansoura University.

It will include 100 patients with lupus nephritis, Diagnosis of glomerulonephritis was performed by renal biopsy, and all of the renal biopsies were carried out at urology and nephrology center.

Patients with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2 will be randomized into two groups Study group will receive SGLT2i inhibitor as add on drug or replace another drug according to patient clinical situation, dapagliflozin 10 mg and 25 mg will be used once daily with or without food.

Control group will be maintained on placebo. The primary endpoint will be sustained decline in eGFR ≥50%, ESKD, or kidney or cardiovascular death We will follow up all patients for 12 months and compare their results.

2. Inclusion criteria: Patients aged more than 16 year. Willing to sign informed consent. Diagnosis of Systemic Lupus Erythematosus (SLE) according to american college of rheumatology (ACR) classification criteria.

Renal biopsy showed lupus nephritis. Patient with eGFR > 30 ml/min/1.73m2 by cockcroft-gault equation. 3. Exclusion criteria: Patients with eGFR <30 ml/min per 1.73 m2. Current pregnancy or lactation. Medical history of chronic disease (CLD, cancer, severe respiratory distress, gastrointestinal tract lesions).

Patients refusing to participate in the study or lost follow up. Evidence of urinary obstruction of difficulty in voiding at screening. Patients who are receiving high dose diuretics or combined Angiotensin converting enzymes inhibitors(ACEI) and Angiotensin II receptor blockers (ARBS).

Patients who have frequent hypotensive episode or systolic blood pressure (SBP) <100 mmHg.

Operational design:

Study Protocol:

Patients included in the study will treated with dapaglifilozin initiated at a total daily dosage of 10 mg/kg per day.

Study design:

Type of the study: randomized controlled study.

The following data will be gathered and evaluated for all patients:

I-before intervention:

Serum creatinine, Creatinine clearance. 24 hour urine protein, urine protein/creatinine ratio. Urine analysis. HBA1c. Hemoglobin (HGB). Uric acid and lipid profile. Lupus serology.

II-after intervention: All patients will be evaluated monthly regarding:

Serum creatinine, creatinine clearance. 24 hour proteinuria, protein/creatinine ratio. Fasting, random and postprandial glucose levels. calcineurin inhibitors (CNI) trough level if used. Urine analysis. HGB level. Uric acid, lipid profile. Lupus serology.

Cardiovascular assessment:

Echocardiogram. Atherosclerosis and vascular calcification incidence (NCCT model). Regular measurement of blood pressure each visit

ll patients will be evaluated at 12 month regarding:

1. erythropoetin level
2. Hepcidin level.

Inclusion Criteria:

• Patients aged more than 16 year.
• Willing to sign informed consent.
• Diagnosis of SLE according to EULAR/ACR classification criteria.
• Renal biopsy showed lupus nephritis.
• Patient with eGFR > 30 ml/min/1.73m2 by cockcroft-gault equation.

Exclusion Criteria:

• Patients with eGFR <30 ml/min per 1.73 m2.
• Current pregnancy or lactation.
• Medical history of chronic disease (CLD, cancer, severe respiratory distress, gastrointestinal tract lesions).
• Patients refusing to participate in the study or lost follow up.
• Evidence of urinary obstruction of difficulty in voiding at screening.
• Patients who are receiving high dose diuretics or combined ACEI, Angiotensin II receptor blockers (ARBS).
• Patients who have frequent hypotensive episode or SBP <100 mmHg.

all individual participant data (IPD) that underlie results in a publication

1 year

1 year

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