Dapagliflozin in Living-Donor Kidney Transplant Recipients (DAPA-GRAFT)

Effect of Dapagliflozin on Kidney Allograft Function in Living-Donor Kidney Transplant Recipients: A Randomized Open-Label Clinical Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Kidney Transplant Failure; Kidney Transplant
• Intervention / Treatment: Drug: Dapagliflozin (10mg Tab); Other: Standard of Care

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 Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44250
      • Universidad de Guadalajara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin Group; Dapagliflozin 10 mg orally once daily administered in addition to standard immunosuppressive therapy for 12 months.	Drug: Dapagliflozin (10mg Tab); Dapagliflozin 10 mg orally once daily administered in addition to standard immunosuppressive therapy for 12 months.
Active Comparator: Control Group; Standard post-transplant medical therapy without SGLT2 inhibitor.	Other: Standard 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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,	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibrosis	Percentage of interstitial fibrosis on kidney allograft biopsy	12 months
Acute Rejection	Number of participants with biopsy-proven acute rejection	12 months
Blood Pressure	Systolic and diastolic blood pressure measured in millimeters of mercury (mmHg) using a calibrated sphygmomanometer during clinical visits.	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.	Baseline to 12 months.
Change in E/e' ratio	E/e' ratio measured by Doppler echocardiography as an estimate of left ventricular filling pressures.	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.	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.	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	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.	Baseline to 12 months
Incidence of cardiovascular events	Number of participants with cardiovascular events, including hospitalization for heart failure, myocardial infarction, or cardiovascular death.	12 months
Urinary Tract Infections	Number of participants with urinary tract infections	12 months
Graft Survival	Number of participants with graft survival at 12 months	12 months
Hemoglobin	Change in hemoglobin levels.expressed in g/dL .	Baseline, 3, 6 , 12 months
Hematocrit	Change in hematocrit expressed as percentage (%).	Baseline, 3, 6 and 12 months,
Fasting Glucose	Change in fasting plasma glucose levels expressed in mg/dL	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.	Baseline, 6 and 12 months
Nitric Oxide	Changes in nitric oxide levels from baseline to 12 months, expressed in µmol/L	Baseline, 3 and 6 months.
Lipid peroxidation	Changes in lipid peroxidation expressed as malondialdehyde (MDA), nmol/mL.	Baseline, 3 and 6 months
Superoxide Dismutase Activity (SOD)	Change in Superoxide Dismutase Activity (SOD) expressed in U/mL	Baseline, 3, and 6 months
Glutathione Peroxidase Activity (GPx)	Change in Glutathione Peroxidase Activity (GPx), expressed as U/L.	Baseline, 3 and 6 months
Total Antioxidant Capacity (TAC)	Change in Total antioxidant capacity (TAC) expressed as Units	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.	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.	Baseline, 3 and 6 months
Toll-like receptor 2 (TLR2)	Changes in toll-like receptor 2 (TLR2)e xpressed in pg/mL	Baseline, 3 and 6 months
Toll-like receptor 2 (TLR4)	Changes in toll-like receptor 2 (TLR4) expressed in pg/mL	Baseline, 3 and 6 months

Collaborators and Investigators

• Sponsor: University of Guadalajara
• Collaborators: Instituto Mexicano del Seguro Social
• Investigators: Principal Investigator: Jorge Andrade Sierra, PhD, Hospital de Especialidades del Centro Medico Nacional de Occidente IMSS

Publications and helpful links

General Publications

• Novikova MS, Minushkina LO, Allazova SS, Zateyshchikov DA, Boeva OI, Kotenko ON, Vinogradov VE, Shilov EM, Antsiferov MB, Koteshkova OM, Molina LP. Efficacy and Safety of Sglt-2 Inhibitors In Renal Allograft Recipients: an Open-Label, Single-Center Prospective Study. Kardiologiia. 2025 Oct 23;65(9):10-18. doi: 10.18087/cardio.2025.9.n2952. English, Russian.
• Demir ME, Helvaci O, Yildirim T, Merhametsiz O, Sezer S. Potential Role of SGLT-2 Inhibitors in Improving Allograft Function and Reducing Rejection in Kidney Transplantation. Clin Transplant. 2025 Sep;39(9):e70233. doi: 10.1111/ctr.70233.
• Demir ME, Ozler TE, Merhametsiz O, Sozener U, Uyar M, Ercan Z, Bardak Demir S, Sezer S, Turkmen Sariyildiz G. The results of SGLT-2 inhibitors use in kidney transplantation: 1-year experiences from two centers. Int Urol Nephrol. 2023 Nov;55(11):2989-2999. doi: 10.1007/s11255-023-03645-7. Epub 2023 Jun 8.
• Song CC, Brown A, Winstead R, Yakubu I, Demehin M, Kumar D, Gupta G. Early initiation of sodium-glucose linked transporter inhibitors (SGLT-2i) and associated metabolic and electrolyte outcomes in diabetic kidney transplant recipients. Endocrinol Diabetes Metab. 2020 Sep 13;4(2):e00185. doi: 10.1002/edm2.185. eCollection 2021 Apr.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: April 23, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Dapagliflozin; Oxidative Stress; Graft Survival; Kidney transplant recipients; Kidney allograft function
• Additional Relevant MeSH Terms: Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care; dapagliflozin
• Other Study ID Numbers: R-2024-1301-159

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be publicly shared to ensure participant confidentiality and comply with institutional and ethical data protection regulations. Study findings will be disseminated in aggregate form through scientific publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No