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NCT Number: NCT04936282

Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients (TRAINING)

Background: Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α klotho levels, progression of IFTA, and loss of kidney function.

Methods: The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-TX, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Kidney Transplant Failure and Rejection Behavior Rejection, Psychology Social Behavior

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Fundación Puigvert, Barcelona, Spain

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients of either sex, older than 18 years, with no immunological risk (PRA<20% and absence of DSA), who receive their first deceased donor or living donor KT.
  • Presence of BL, excluding isolated inflammation (t0, i>0) and isolated tubulitis (t>0, i0).
  • Patients receiving tacrolimus in combination with mycophenolic acid (MPA) and steroids.
  • Absence of clinical or subclinical and histological immunological dysfunction before randomization.
  • Absence of de novo DSA anti-HLA antibodies at the time of randomization.
  • Provision of written informed consent.
  • Acceptance of efficient contraception in women.

Exclusion criteria

  • Recipients of a multi-organ transplant.
  • Re-transplants.
  • Patients without inflammation in the third month protocol biopsy (i0,t0), or with isolated inflammation without tubulitis (t0,i>0) or isolated tubulitis without inflammation (t>0,i0).
  • Presence of DSA antibodies before transplantation or at randomization.
  • Cold ischemia time >30 hours.
  • Serum creatinine >2.5 mg/dl or proteinuria >1 g/day at randomization.
  • Presence of significant thrombopenia (<100,000/mm3) or leukopenia (<3000 mm/3) at randomization.
  • Previous episode of clinical or subclinical rejection (≥IA) before randomization.
  • CMV disease in the first three months after transplantation.
  • BK-polyomavirus nephropathy at randomization.
  • Recurrent or de novo glomerulonephritis.
  • Treatment with immunosuppressive drugs other than those in this clinical trial.
  • Patients who are positive for the human immunodeficiency virus (HIV) or with severe systemic infection, who, in the opinion of the investigator, require continued therapy.
  • Previous (within the last 5 years) or present malignancy, except excised basal or squamous cell carcinoma.

Treatment and study plan

Grafalon

Drug

When Borderline lesions are present in protocol biopsy, administer Grafalon ® 6 mg/kg/day in a single day. Then continue with the normal treatment: Steroids (5 mg/day), tacrolimus (0.1 mg/kg/day) and mycophenolate (1000 mg/day).

Normal Treatment

Drug

When Borderline lesions are present in protocol biopsy, administer the normal treatment: Steroids (5 mg/day), tacrolimus (0.1 mg/kg/day) and mycophenolate (1000 mg/day)

Primary outcomes

  1. Presence of interstitial fibrosis/tubular atrophy (IFTA)

    Time frame: 24 months

    Measurement at 24 months according to the Banff classification. The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of biopsies from solid organ transplant.

  2. Renal function measured with CKD-EPI

    Time frame: 24 months

    Renal function after kidney transplant in both groups at 24 months measured according to glomerular filtration rate determined by CKD-EPI formula

Secondary outcomes

  1. Graft Survival

    Time frame: 24 months

    Graft survival after kidney transplant in both groups

  2. Patient Survival

    Time frame: 24 months

    Patient survival after kidney transplant in both groups

  3. Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups

    Time frame: 24 months

    The Basle scale was used to assess adherence to immunosuppressive therapy.

  4. Incidence of Diabetes Mellitus

    Time frame: 24 months

    Incidence of diabetes mellitus after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months

  5. Blood Pressure mmHg

    Time frame: 24 months

    Blood pressure after kidney transplant in both groups at 24 months

  6. Number of Participants With Acute Rejection Lesions

    Time frame: 24 months

    Patients with acute rejection lesions (including subclinical rejection) at 24 months according to Banff classification

  7. Lipid Profile cholesterol, triglycerides

    Time frame: 24 months

    Lipid profile after kidney transplant in both groups at 24 months

  8. Klotho levels pg/ml

    Time frame: 24 months

    Klotho levels after kidney transplant in both groups at 1, 3, 6, 12 and 24 months

Sponsors and collaborators

Lead sponsor

Fundación Canaria Instituto de Investigación Sanitaria de Canarias

Other

Registry information

Official study title

Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients: a Spanish Multicenter, Randomized, Controlled Parallel-group Trial: The TRAINING Study

Important dates

Study start
2022
Primary completion
2027
Study completion
2027
First posted
Jun 23, 2021
Registry last updated
Sep 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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