Treatment of early borderline lesions in low immunological risk kidney transplant patients: a Spanish multicenter, randomized, controlled parallel-group study protocol: the TRAINING study

• Published in: BMC nephrology 2022-11, Vol.23 (1), p.1-357, Article 357
• Main Authors: Hernández, Domingo, Vázquez-Sánchez, Teresa, Sola, Eugenia, Lopez, Veronica, Ruiz-Esteban, Pedro, Caballero, Abelardo, Salido, Eduardo, Leon, Myriam, Rodriguez, Aurelio, Serra, Nuria, Rodriguez, Consuelo, Facundo, Carme, Perello, Manel, Silva, Irene, Marrero-Miranda, Domingo, Cidraque, Ignacio, Moreso, Francesc, Guirado, Luis, Serón, Daniel, Torres, Armando
• Format: Article
• Language: English
• Subjects: Antilymphocyte serum; Antithymocyte globulin; Atrophy; Biopsy; borderline lesions; Clinical trials; Cytokines; Fibrosis; Globulins; Health aspects; Immunocompromised host; Immunology; Inflammation; kidney transplant; Kidney transplantation; Kidney transplants; Kidneys; Klotho protein; Lesions; Measurement; Nephrology; Patients; Prevention; Pulmonary fibrosis; Renal function; Risk factors; Senescence; Steroid hormones; Steroids; Study Protocol; subclinical inflammation; Thymocytes; Transplantation; Transplants & implants; α-klotho, low immunological risk
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-022-02989-z

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 [alpha]-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in [alpha]-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[R]) (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[R] 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[R] treatment in low-immunological-risk KT patients with early BL. Trial registration clinicaltrials.gov: NCT04936282. Registered June 23, 2021, Keywords: kidney transplant, borderline lesions, [alpha]-klotho, low immunological risk, subclinical inflammation