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.

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.