Kidney Transplant, Kidney Transplant Failure
Conditions
Keywords
Dapagliflozin, Kidney transplant recipients, Kidney allograft function, Oxidative Stress, Graft Survival
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.
Interventions
Dapagliflozin 10 mg orally once daily administered in addition to standard immunosuppressive therapy for 12 months.
OTHERStandard of Care
Participants receive standard immunosuppressive therapy and routine post-kidney transplant clinical management according to institutional protocols during the 12-month follow-up period.
Sponsors
University of Guadalajara
Instituto Mexicano del Seguro Social
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel assignment. Participants are randomized to receive dapagliflozin plus standard of care or standard of care alone, and outcomes are assessed prospectively over the follow-up period
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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) * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in estimated glomerular filtration rate (eGFR) | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Fibrosis | 12 months | Percentage of interstitial fibrosis on kidney allograft biopsy |
| Acute Rejection | 12 months | Number of participants with biopsy-proven acute rejection |
| Blood Pressure | Baseline, 3, 6 ,12 months | Systolic and diastolic blood pressure measured in millimeters of mercury (mmHg) using a calibrated sphygmomanometer during clinical visits. |
| Change in left ventricular ejection fraction (LVEF) | Baseline to 12 months. | Left ventricular ejection fraction (LVEF), expressed as percentage (%), measured by transthoracic echocardiography using Simpson's biplane method. |
| Change in E/e' ratio | Baseline to 12 months | E/e' ratio measured by Doppler echocardiography as an estimate of left ventricular filling pressures. |
| Change in pulmonary artery systolic pressure (PASP) | Baseline to 12 months | Pulmonary artery systolic pressure (PASP), expressed in mmHg, estimated by transthoracic echocardiography using tricuspid regurgitation velocity and standard echocardiographic methods. |
| Change in left ventricular mass index (LVMI) | Baseline to 12 months | Left ventricular mass index (g/m²) measured by transthoracic echocardiography according to standardized guidelines. |
| Change in tricuspid annular plane systolic excursion (TAPSE) | Baseline to 12 months | TAPSE, expressed in millimeters (mm), measured by M-mode echocardiography as an indicator of right ventricular systolic function |
| Change in left atrial volume index (LAVI) | Baseline to 12 months | Left atrial volume index (LAVI), expressed in mL/m², measured by transthoracic echocardiography using the biplane area-length method. |
| Incidence of cardiovascular events | 12 months | Number of participants with cardiovascular events, including hospitalization for heart failure, myocardial infarction, or cardiovascular death. |
| Urinary Tract Infections | 12 months | Number of participants with urinary tract infections |
| Graft Survival | 12 months | Number of participants with graft survival at 12 months |
| Hemoglobin | Baseline, 3, 6 , 12 months | Change in hemoglobin levels.expressed in g/dL . |
| Hematocrit | Baseline, 3, 6 and 12 months, | Change in hematocrit expressed as percentage (%). |
| Fasting Glucose | Baseline, 3, 6, 12 months, | Change in fasting plasma glucose levels expressed in mg/dL |
| Change in HbA1c | Baseline, 6 and 12 months | Change in glycated hemoglobin (HbA1c) from baseline, 6 and 12 months in participants with diabetes mellitus, expressed in percentaje. |
| Nitric Oxide | Baseline, 3 and 6 months. | Changes in nitric oxide levels from baseline to 12 months, expressed in µmol/L |
| Lipid peroxidation | Baseline, 3 and 6 months | Changes in lipid peroxidation expressed as malondialdehyde (MDA), nmol/mL. |
| Superoxide Dismutase Activity (SOD) | Baseline, 3, and 6 months | Change in Superoxide Dismutase Activity (SOD) expressed in U/mL |
| Glutathione Peroxidase Activity (GPx) | Baseline, 3 and 6 months | Change in Glutathione Peroxidase Activity (GPx), expressed as U/L. |
| Total Antioxidant Capacity (TAC) | Baseline, 3 and 6 months | Change in Total antioxidant capacity (TAC) expressed as Units |
| 8-hydroxy-2'-deoxyguanosine (8-OHdG) | Baseline, 3 and 6 months | Change in 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels from baseline to 12 months, expressed in ng/mL. |
| 8-oxoguanine glycosylase (OGG1) | Baseline, 3 and 6 months | Change in 8-oxoguanine glycosylase (OGG1) levels from baseline to 12 months expressed in ng/mL. |
| Toll-like receptor 2 (TLR2) | Baseline, 3 and 6 months | Changes in toll-like receptor 2 (TLR2)e xpressed in pg/mL |
| Toll-like receptor 2 (TLR4) | Baseline, 3 and 6 months | Changes in toll-like receptor 2 (TLR4) expressed in pg/mL |
Countries
Mexico
Contacts
PRINCIPAL_INVESTIGATORJorge Andrade Sierra, PhD
Hospital de Especialidades del Centro Medico Nacional de Occidente IMSS
Outcome results
None listed