Effect of Dapagliflozin on Renal Outcomes and Bone Mineral Disease in Non-diabetic Chronic Kidney Disease Patients

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?