It is a randomized controlled trial in which 100 non diabetic chronic kidney disease (CKD) patient is being participated.

Their estimated glomerular filtration rate (eGFR) between 25-75 ml/min/1.73 m2.

Participants will be randomized into two groups:

• Study group: includes 50 patients, they will receive Sodium glucose co-transporter 2 inhibitor (SGLT2i) as add on drug, Dapagliflozin 10 mg will be used once daily with or without food.
• Control group: includes 50 patients, they will receive placebo their medication.

The investigators will follow up all patients for 12 months and compare their results.

This study aims to:

1. Assess SGLT2i role in delaying the progression of ongoing chronic kidney disease.
2. Study the impact of SGLT2i on bone and mineral metabolism in this patients' population.

All patients have been recruited from the renal clinic of Nephrology and transplantation unit. The entire study will be conducted at Urology and Nephrology center in Mansoura University.

Study design and sample size:

• Sample size: Was calculated based on previous research by (DAPA-CKD) study using G. power program with α error 0.05 and power 80% and it was equal to approximately 98 patients.

Type of the study: Randomized, controlled trial.

Patient's enrollment: 100 patients with non-diabetic CKD with an estimated glomerular filtration rate (eGFR) of 25-75 ml/min/1.73m2 will be randomized into two groups:

• Study group: includes 50 patients, they will receive SGLT2i as add on drug, Dapagliflozin 10 mg will be used once daily with or without food.
• Control group: includes 50 patients, they will receive placebo plus their medication.

The investigators will follow up all patients for 12 months and compare their results.

Study Protocol:

• 100 patients will be included in the study. Patients will be randomized 1:1, either to a control group receiving placebo and an intervention group receiving 10 mg dapagliflozin daily.

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

I- Baseline evaluation:

• Patients of both groups will be subjected to full history taking including duration and cause of CKD and drug history and routine clinical examination.

• Laboratory investigations:

  1. Serum creatinine, calcium, phosphorus and magnesium.

  2. 24 hour urine protein, Creatinine clearance, calcium and phosphorus

  3. Urine analysis with microscopy and random urine protein/creatinine ratio.

  4. Random blood sugar.

  5. Intact parathyroid hormone (iPTH).

  6. Urine pregnancy test for females in child bearing period.

  7. Bone turnover markers:

     1. Bone-specific alkaline phosphatase (BALP).
     2. Propeptides of type I procollagen (P1NP).
     3. Carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-1).
     4. Tartrate-resistant acid phosphatase (TRAP-5b).

• Radiological investigation:

Quantitative computed tomography: to detect cortical and trabecular bone density.

II-Evaluation throughout the study:

All patients will be evaluated every 3 months thereafter regarding:

• Thorough clinical evaluation including regular measurement of blood pressure and assessment of volume status each visit.

• Laboratory investigations:

  1. Serum creatinine, calcium, phosphorus and magnesium.
  2. 24 hour urine protein, Creatinine clearance, calcium and phosphorus
  3. Urine analysis with microscopy and random urine protein/creatinine ratio.
  4. Random blood sugar.

All patients will be evaluated at 12 month regarding:

1. iPTH

2. Bone turnover markers:

   • Bone-specific alkaline phosphatase (BALP)
   • Propeptides of type I procollagen (P1NP).
   • Carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-1).
   • Tartrate-resistant acid phosphatase (TRAP-5b).

3. Quantitative computed tomography (QCT).

The main research question is: Does use of SGLT2i will slow down the progression of CKD in patients without diabetes? Will the use of SGLT2i have a negative impact on bone and mineral metabolism among these patients?

Inclusion Criteria:

1. Patients aged more than 18 year.
2. CKD patient with eGFR from 25 to 75 ml/min/1.73m2 with no evidence of acute drop of the GFR in the last 3 months.
3. Willing to sign informed consent.

Exclusion Criteria:

1. eGFR less than 25 ml/min per 1.73 m2.
2. Medical history of chronic disease (diabetes mellitus, chronic liver and/or respiratory diseases).
3. Patients with primary or secondary glomerulonephritis/ nephrotic syndrome (proteinuria ≥ 3.5 gm/day) and/or any evidence of active immunological/ collagen vascular disease.
4. Inability to sign the study consent form or refusal to participate in the study.
5. Evidence of urinary obstruction.
6. Patients with evidence of volume depletion or receiving a combination of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBS)..
7. Patients with current history of frequent hypotensive episodes or systolic blood pressure <100 mmHg.
8. Patients with history of recurrent urinary tract infection and/or valvovaginitis
9. Patients with ongoing active malignancy.
10. Patients with any evidence of active infection including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and tuberculosis (TB).
11. Current or previous organ transplantation, or expected to get a kidney transplant within 12 months.
12. Patients who received any SGLT2i for more than 3 months in the past.
13. Patients who are already on medications that may affect or interact with bone metabolism such as bisphosphonates, calcitonin, steroid, denosumab and estrogen during the last 6 months.
14. Pregnant and/or lactating woman.

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