Bortezomib in late antibody-mediated kidney transplant rejection BORTEJECT Study: study protocol for a randomized controlled trialReport as inadecuate




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Trials

, 15:107

First Online: 03 April 2014Received: 15 October 2013Accepted: 10 March 2014DOI: 10.1186-1745-6215-15-107

Cite this article as: Eskandary, F., Bond, G., Schwaiger, E. et al. Trials 2014 15: 107. doi:10.1186-1745-6215-15-107

Abstract

BackgroundDespite major advances in transplant medicine, improvements in long-term kidney allograft survival have not been commensurate with those observed shortly after transplantation. The formation of donor-specific antibodies DSA and ongoing antibody-mediated rejection AMR processes may critically contribute to late graft loss. However, appropriate treatment for late AMR has not yet been defined. There is accumulating evidence that the proteasome inhibitor bortezomib may substantially affect the function and integrity of alloantibody-secreting plasma cells. The impact of this agent on the course of late AMR has not so far been systematically investigated.

Methods-designThe BORTEJECT Study is a randomized controlled trial designed to clarify the impact of intravenous bortezomib on the course of late AMR. In this single-center study nephrological outpatient service, Medical University Vienna we plan an initial cross-sectional DSA screening of 1,000 kidney transplant recipients functioning graft at ≥180 days; estimated glomerular filtration rate eGFR >20 ml-minute-1.73 m. DSA-positive recipients will be subjected to kidney allograft biopsy to detect morphological features consistent with AMR. Forty-four patients with biopsy-proven AMR will then be included in a double-blind placebo-controlled intervention trial 1:1 randomization stratified for eGFR and the presence of T-cell-mediated rejection. Patients in the active group will receive two cycles of bortezomib 4 × 1.3 mg-m over 2 weeks; 3-month interval between cycles. The primary end point will be the course of eGFR over 24 months intention-to-treat analysis. The sample size was calculated according to the assumption of a 5 ml-minute-1.73 m difference in eGFR slope per year between the two groups alpha: 0.05; power: 0.8. Secondary endpoints will be DSA levels, protein excretion, measured glomerular filtration rate, transplant and patient survival, and the development of acute and chronic morphological lesions in 24-month protocol biopsies.

DiscussionThe impact of anti-humoral treatment on the course of late AMR has not yet been systematically investigated. Based on the hypothesis that proteasome inhibition improves the outcome of DSA-positive late AMR, we suggest that our trial has the potential to provide solid evidence towards the treatment of this type of rejection.

Trial registrationClinicaltrials.gov: NCT01873157.

KeywordsAntibody-mediated rejection Donor-specific antibody Bortezomib Kidney transplantation Proteasome inhibition AbbreviationsAMRantibody-mediated rejection

C4dC4 complement split product deposition

DSAdonor-specific antibodies

eGFRestimated glomerular filtration rate

GFRglomerular filtration rate

HLAhuman leukocyte antigen

IVIGintravenous immunoglobulin.

Electronic supplementary materialThe online version of this article doi:10.1186-1745-6215-15-107 contains supplementary material, which is available to authorized users.

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Author: Farsad Eskandary - Gregor Bond - Elisabeth Schwaiger - Zeljko Kikic - Christine Winzer - Markus Wahrmann - Lena Marinova -

Source: https://link.springer.com/







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