Dapagliflozin in Living-Donor Kidney Transplant Recipients

Phase 2Active Not RecruitingNCT07555106

University of Guadalajara54 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

* 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.

Outcomes

Primary Outcomes

Change in estimated glomerular filtration rate (eGFR)

Change in estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI equation and expressed in mL/min/1.73 m².

Time frame: Baseline to 12 months

Change in urinary albumin-to-creatinine ratio (UACR)

Change in albuminuria assessed by urinary albumin-to-creatinine ratio (UACR) and expressed in mg/g, from baseline to 12 months,

Time frame: Baseline to 12 months

Secondary Outcomes

Fibrosis

Percentage of interstitial fibrosis on kidney allograft biopsy

Time frame: 12 months

Acute Rejection

Number of participants with biopsy-proven acute rejection

Time frame: 12 months

Blood Pressure

Systolic and diastolic blood pressure measured in millimeters of mercury (mmHg) using a calibrated sphygmomanometer during clinical visits.

Time frame: Baseline, 3, 6 ,12 months

Change in left ventricular ejection fraction (LVEF)

Left ventricular ejection fraction (LVEF), expressed as percentage (%), measured by transthoracic echocardiography using Simpson's biplane method.

Time frame: Baseline to 12 months.

Change in E/e' ratio

E/e' ratio measured by Doppler echocardiography as an estimate of left ventricular filling pressures.

Time frame: Baseline to 12 months

Change in pulmonary artery systolic pressure (PASP)

Pulmonary artery systolic pressure (PASP), expressed in mmHg, estimated by transthoracic echocardiography using tricuspid regurgitation velocity and standard echocardiographic methods.

Time frame: Baseline to 12 months

Change in left ventricular mass index (LVMI)

Left ventricular mass index (g/m²) measured by transthoracic echocardiography according to standardized guidelines.

Time frame: Baseline to 12 months

Change in tricuspid annular plane systolic excursion (TAPSE)

TAPSE, expressed in millimeters (mm), measured by M-mode echocardiography as an indicator of right ventricular systolic function

Time frame: Baseline to 12 months

Change in left atrial volume index (LAVI)

Left atrial volume index (LAVI), expressed in mL/m², measured by transthoracic echocardiography using the biplane area-length method.

Time frame: Baseline to 12 months

Incidence of cardiovascular events

Number of participants with cardiovascular events, including hospitalization for heart failure, myocardial infarction, or cardiovascular death.

Time frame: 12 months

Urinary Tract Infections

Number of participants with urinary tract infections

Time frame: 12 months

Graft Survival

Number of participants with graft survival at 12 months

Time frame: 12 months

Hemoglobin

Change in hemoglobin levels.expressed in g/dL .

Time frame: Baseline, 3, 6 , 12 months

Hematocrit

Change in hematocrit expressed as percentage (%).

Time frame: Baseline, 3, 6 and 12 months,

Fasting Glucose

Change in fasting plasma glucose levels expressed in mg/dL

Time frame: Baseline, 3, 6, 12 months,

Change in HbA1c

Change in glycated hemoglobin (HbA1c) from baseline, 6 and 12 months in participants with diabetes mellitus, expressed in percentaje.

Time frame: Baseline, 6 and 12 months

Nitric Oxide

Changes in nitric oxide levels from baseline to 12 months, expressed in µmol/L

Time frame: Baseline, 3 and 6 months.

Lipid peroxidation

Changes in lipid peroxidation expressed as malondialdehyde (MDA), nmol/mL.

Time frame: Baseline, 3 and 6 months

Superoxide Dismutase Activity (SOD)

Change in Superoxide Dismutase Activity (SOD) expressed in U/mL

Time frame: Baseline, 3, and 6 months

Glutathione Peroxidase Activity (GPx)

Change in Glutathione Peroxidase Activity (GPx), expressed as U/L.

Time frame: Baseline, 3 and 6 months

Total Antioxidant Capacity (TAC)

Change in Total antioxidant capacity (TAC) expressed as Units

Time frame: Baseline, 3 and 6 months

8-hydroxy-2'-deoxyguanosine (8-OHdG)

Change in 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels from baseline to 12 months, expressed in ng/mL.

Time frame: Baseline, 3 and 6 months

8-oxoguanine glycosylase (OGG1)

Change in 8-oxoguanine glycosylase (OGG1) levels from baseline to 12 months expressed in ng/mL.

Time frame: Baseline, 3 and 6 months

Toll-like receptor 2 (TLR2)

Changes in toll-like receptor 2 (TLR2)e xpressed in pg/mL

Time frame: Baseline, 3 and 6 months

Toll-like receptor 2 (TLR4)

Changes in toll-like receptor 2 (TLR4) expressed in pg/mL

Time frame: Baseline, 3 and 6 months

Dapagliflozin in Living-Donor Kidney Transplant Recipients

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes