Effect of Dapagliflozin on Kidney Allograft Function in Living-Donor Kidney Transplant Recipients: A Randomized Open-Label Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Change in estimated glomerular filtration rate (eGFR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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)
- •Antibody-mediated rejection (AMR) or Banff grade ≥2A acute cellular rejection during the first week post-transplant
- •Use of anticoagulants, nonsteroidal anti-inflammatory drugs, pentoxifylline, or mineralocorticoid receptor antagonists (spironolactone, eplerenone, finerenone)
- •Highly sensitized recipients or presence of donor-specific antibodies prior to enrollment
- •Urological disorders (including recurrent urinary tract infections or urolithiasis within 12 months prior to enrollment) or severe genital infections
- •Presence of de novo or recurrent glomerulopathy or BK virus nephropathy during the first week post-transplant.
研究组 & 干预措施
Dapagliflozin Group
Dapagliflozin 10 mg orally once daily administered in addition to standard immunosuppressive therapy for 12 months.
干预措施: Dapagliflozin (10mg Tab) (Drug)
Control Group
Standard post-transplant medical therapy without SGLT2 inhibitor.
干预措施: Standard of Care (Other)
结局指标
主要结局
Change in estimated glomerular filtration rate (eGFR)
时间窗: 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)
时间窗: 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,
次要结局
- 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)