Treatment for early borderline lesions in low immunological risk kidney transplant patients

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

This study is testing whether treating early kidney issues in low-risk transplant patients with a new medication can help protect their kidney function and health.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fundación Canaria de Investigación Sanitaria (Academic / other)
• Locations: 4 sites (Tenerife, None Selected and 3 other locations)
• Trial ID: NCT04936282 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of treating borderline lesions in kidney transplant patients who are at low immunological risk. It will involve randomizing 80 patients to receive either Grafalon or standard treatment to assess the impact on renal function and graft histology. The focus is on understanding whether addressing these lesions can prevent further kidney damage and loss of function. The study is particularly interested in the role of α-klotho, a protein with antifibrotic properties, in managing inflammation and preserving kidney health.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 years old who have received their first kidney transplant and have borderline lesions without significant immunological risk.

Not a fit: Patients who have received multi-organ transplants or have a history of significant immunological dysfunction will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve kidney function and prolong graft survival in patients with borderline lesions.

How similar studies have performed: While few controlled studies have analyzed the therapeutic benefit of borderline lesions, the approach of using Grafalon in this context is relatively novel.

Eligibility criteria

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.

Where this trial is running

Tenerife, None Selected and 3 other locations

• Hospital Universitario de Canarias — Tenerife, None Selected, Spain (Recruiting)
• Fundación Puigvert — Barcelona, Spain (Recruiting)
• Hospital Universitari Valld´Hebron — Barcelona, Spain (Recruiting)
• Veronica Lopez Jimenez — Malaga, Spain (Recruiting)

Study contacts

• Study coordinator: Pedro Ruiz-Esteban, PhD

Conditions Kidney Transplant Failure and Rejection; borderline lesions; α-klotho; low immunological risk; subclinical inflammation; kidney transplant