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. 2022 Nov 7;23(1):357.
doi: 10.1186/s12882-022-02989-z.

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

Domingo Hernández #  1   2 , Teresa Vázquez-Sánchez #  3 , Eugenia Sola  3 , Veronica Lopez  3 , Pedro Ruiz-Esteban  3 , Abelardo Caballero  4 , Eduardo Salido  5 , Myriam Leon  6 , Aurelio Rodriguez  7 , Nuria Serra  8 , Consuelo Rodriguez  7 , Carme Facundo  8 , Manel Perello  9 , Irene Silva  8 , Domingo Marrero-Miranda  7 , Ignacio Cidraque  9 , Francesc Moreso  9 , Luis Guirado  8 , Daniel Serón #  9 , Armando Torres #  7
Affiliations

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

Domingo Hernández et al. BMC Nephrol. .

Abstract

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 .

Keywords: borderline lesions; kidney transplant; subclinical inflammation; α-klotho, low immunological risk.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Scheme and determinations of the study
See this image and copyright information in PMC

References

    1. Hariharan S, Israni AK, Danovitch G. Long-Term Survival after Kidney Transplantation. N Engl J Med. 2021;385(8):729–743. doi: 10.1056/NEJMra2014530. - DOI - PubMed
    1. Riella LV, Djamali A, Pascual J. Chronic allograft injury: Mechanisms and potential treatment targets. Transplant Rev (Orlando) 2017;31(1):1–9. doi: 10.1016/j.trre.2016.10.005. - DOI - PubMed
    1. Kasiske BL, Gaston RS, Gourishankar S, Halloran PF, Matas AJ, Jeffery J, Rush D. Long-term deterioration of kidney allograft function. Am J Transplant. 2005;5(6):1405–1414. doi: 10.1111/j.1600-6143.2005.00853.x. - DOI - PubMed
    1. Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003;349(24):2326–2333. doi: 10.1056/NEJMoa020009. - DOI - PubMed
    1. García-Carro C, Dörje C, Åsberg A, Midtvedt K, Scott H, Reinholt FP, Holdaas H, Seron D, Reisæter AV. Inflammation in Early Kidney Allograft Surveillance Biopsies With and Without Associated Tubulointerstitial Chronic Damage as a Predictor of Fibrosis Progression and Development of De Novo Donor Specific Antibodies. Transplantation. 2017;101(6):1410–1415. doi: 10.1097/TP.0000000000001216. - DOI - PubMed

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