A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection.

Autor:	Eskandary F; Division of Nephrology and Dialysis, Department of Medicine III., Regele H; Departments of Pathology., Baumann L; Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria., Bond G; Division of Nephrology and Dialysis, Department of Medicine III., Kozakowski N; Departments of Pathology., Wahrmann M; Division of Nephrology and Dialysis, Department of Medicine III., Hidalgo LG; Department of Laboratory Medicine and Pathology and., Haslacher H; Laboratory Medicine, and., Kaltenecker CC; Division of Nephrology and Dialysis, Department of Medicine III., Aretin MB; Pharmacy Department, General Hospital Vienna, Vienna, Austria., Oberbauer R; Division of Nephrology and Dialysis, Department of Medicine III., Posch M; Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria., Staudenherz A; Biomedical Imaging and Image-Guided Therapy, and., Handisurya A; Division of Nephrology and Dialysis, Department of Medicine III., Reeve J; Alberta Transplant Applied Genomics Centre, University of Alberta, Edmonton, Alberta, Canada; and., Halloran PF; Alberta Transplant Applied Genomics Centre, University of Alberta, Edmonton, Alberta, Canada; and., Böhmig GA; Division of Nephrology and Dialysis, Department of Medicine III, georg.boehmig@meduniwien.ac.at.
Jazyk:	angličtina
Zdroj:	Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2018 Feb; Vol. 29 (2), pp. 591-605. Date of Electronic Publication: 2017 Dec 14.
DOI:	10.1681/ASN.2017070818
Abstrakt:	Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m 2 intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)-positive ABMR. Forty-four DSA-positive kidney transplant recipients with characteristic ABMR morphology (median time after transplant, 5.0 years; pretransplant DSA documented in 19 recipients), who were identified on cross-sectional screening of 741 patients, were randomly assigned to receive bortezomib ( n =21) or placebo ( n =23). The 0.5-ml/min per 1.73 m 2 per year (95% confidence interval, -4.8 to 5.8) difference detected between bortezomib and placebo in eGFR slope (primary end point) was not significant ( P =0.86). We detected no significant differences between bortezomib- and placebo-treated groups in median measured GFR at 24 months (33 versus 42 ml/min per 1.73 m 2 ; P =0.31), 2-year graft survival (81% versus 96%; P =0.12), urinary protein concentration, DSA levels, or morphologic or molecular rejection phenotypes in 24-month follow-up biopsy specimens. Bortezomib, however, associated with gastrointestinal and hematologic toxicity. In conclusion, our trial failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA, despite significant toxicity. Our results reinforce the need for systematic trials to dissect the efficiency and safety of new treatments for late ABMR. (Copyright © 2018 by the American Society of Nephrology.)
Databáze:	MEDLINE
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