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 treating 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-KT, 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. Discussion: This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL. Trial registration: clinicaltrials.gov: NCT04936282. Registered June 23, 2021, https://clinicaltrials.gov/ct2/show/NCT04936282?term=NCT04936282&draw=2&rank=1. Protocol Version 2 of 21 January 2022. Sponsor: Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). mgomez@fciisc.org.

Systemic treatment of advanced renal cell carcinoma (RCC) after kidney transplantation requires balancing cancer control against allograft injury and immunosuppression. We searched PubMed, Ovid Embase, Scopus, Web of Science, and ClinicalTrials.gov in April 2026, with reruns on 13 August and 19 October 2026. We separated RCC-specific transplant reports from mixed-cancer transplant and non-transplant studies. Direct evidence comprised mainly case reports and retro-spective cohorts with incomplete outcomes and possible overlap. No prospective kidney-transplant-specific RCC study was identified. Vascular endothelial growth factor receptor–targeted tyrosine kinase inhibitors achieved tumor control in selected reports, but renal toxicity and interactions limited safety conclusions. Indications for mechanistic target of rapamycin in-hibitors (RCC treatment or immunosuppression) were often unclear. Concurrent therapies com-plicated response attribution. Immune checkpoint inhibitor outcomes ranged from tumor control with preserved graft function to rejection, irreversible graft loss, dialysis, graft intolerance, or nephrectomy. An unvalidated multidisciplinary framework integrates tumor site and lineage, histology, performance status, immunosuppression, and patient priorities. It distinguishes func-tioning or failing grafts, irreversibly failed retained grafts, and absence of allografts, states that change treatment trade-offs and outcome interpretation. Comparative evidence establishes nei-ther a preferred RCC sequence nor a graft-protective immunosuppressive regimen. Prospective studies should prioritize paired, state-specific cancer and transplant outcomes.