Effect of Dapagliflozin on Kidney Allograft Function in Living-Donor Kidney Transplant Recipients: A Randomized Open-Label Clinical Trial
Overview
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- University of Guadalajara
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- Change in estimated glomerular filtration rate (eGFR)
Overview
Brief Summary
This randomized, open-label, single-center clinical trial aims to evaluate the effect of dapagliflozin on kidney allograft function in adult recipients of a first living-donor kidney transplant. Participants will be randomized to receive dapagliflozin 10 mg daily starting 4 weeks after transplantation or standard care without SGLT2 inhibitor therapy. The primary outcomes include changes in estimated glomerular filtration rate (eGFR) and albuminuria over 12 months. Secondary outcomes include kidney graft histology findings, oxidative stress biomarkers, cardiovascular parameters, infectious events, and kidney graft survival at 12 months.
Detailed Description
Kidney fibrosis is a major pathological mechanism associated with chronic kidney disease progression and kidney allograft dysfunction. Oxidative stress, mitochondrial dysfunction, inflammation, and tissue hypoxia have been implicated in the development of kidney fibrosis.
Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors), including dapagliflozin, have demonstrated kidney-protective and cardiovascular benefits in patients with chronic kidney disease and type 2 diabetes. However, evidence in kidney transplant recipients remains limited, consisting mainly of small observational studies and fews randomized clinical trial.
This study evaluates whether dapagliflozin improves kidney allograft function, reduces albuminuria, modulates oxidative stress biomarkers, and influences kidney graft histological findings during the first year after living-donor kidney transplantation.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Inclusion Criteria:
- •Ability to provide written informed consent
- •Adult patients ≥18 years of age
- •First living-donor kidney transplant recipients
- •Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² at screening
- •Receiving standard immunosuppressive therapy (tacrolimus, mycophenolate mofetil, and prednisone) with induction therapy (thymoglobulin or basiliximab)
Exclusion Criteria
- •Type 1 diabetes mellitus
- •Recipients of deceased donor kidney transplant
- •History of any other solid organ transplant
- •Second kidney transplant
- •Severe cardiovascular disease (congestive heart failure class IV, recent myocardial infarction, unstable angina, stroke, or transient ischemic attack within 8 weeks prior to enrollment)
- •HbA1c \>12% in patients with diabetes mellitus
- •Current use of SGLT2 inhibitors at enrollment
- •Known hypersensitivity or intolerance to SGLT2 inhibitors
- •Pregnant or breastfeeding women
- •Hepatic impairment (AST or ALT \>3 times the upper limit of normal, or total bilirubin \>2 times the upper limit of normal at enrollment)
Arms & Interventions
Dapagliflozin Group
Dapagliflozin 10 mg orally once daily administered in addition to standard immunosuppressive therapy for 12 months.
Intervention: Dapagliflozin (10mg Tab) (Drug)
Control Group
Standard post-transplant medical therapy without SGLT2 inhibitor.
Intervention: Standard of Care (Other)
Outcomes
Primary Outcomes
Change in estimated glomerular filtration rate (eGFR)
Time Frame: Baseline to 12 months
Change in estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI equation and expressed in mL/min/1.73 m².
Change in urinary albumin-to-creatinine ratio (UACR)
Time Frame: Baseline to 12 months
Change in albuminuria assessed by urinary albumin-to-creatinine ratio (UACR) and expressed in mg/g, from baseline to 12 months,
Secondary Outcomes
- Fibrosis(12 months)
- Acute Rejection(12 months)
- Blood Pressure(Baseline, 3, 6 ,12 months)
- Change in left ventricular ejection fraction (LVEF)(Baseline to 12 months.)
- Change in E/e' ratio(Baseline to 12 months)
- Change in pulmonary artery systolic pressure (PASP)(Baseline to 12 months)
- Change in left ventricular mass index (LVMI)(Baseline to 12 months)
- Change in tricuspid annular plane systolic excursion (TAPSE)(Baseline to 12 months)
- Change in left atrial volume index (LAVI)(Baseline to 12 months)
- Incidence of cardiovascular events(12 months)
- Urinary Tract Infections(12 months)
- Graft Survival(12 months)
- Hemoglobin(Baseline, 3, 6 , 12 months)
- Hematocrit(Baseline, 3, 6 and 12 months,)
- Fasting Glucose(Baseline, 3, 6, 12 months,)
- Change in HbA1c(Baseline, 6 and 12 months)
- Nitric Oxide(Baseline, 3 and 6 months.)
- Lipid peroxidation(Baseline, 3 and 6 months)
- Superoxide Dismutase Activity (SOD)(Baseline, 3, and 6 months)
- Glutathione Peroxidase Activity (GPx)(Baseline, 3 and 6 months)
- Total Antioxidant Capacity (TAC)(Baseline, 3 and 6 months)
- 8-hydroxy-2'-deoxyguanosine (8-OHdG)(Baseline, 3 and 6 months)
- 8-oxoguanine glycosylase (OGG1)(Baseline, 3 and 6 months)
- Toll-like receptor 2 (TLR2)(Baseline, 3 and 6 months)
- Toll-like receptor 2 (TLR4)(Baseline, 3 and 6 months)