ABSTRACT
Introduction
Antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Its therapy continues to be challenge, and no treatment has been approved for the market thus far.
Areas covered
In this article, we discuss the pathophysiology and phenotypic presentation of ABMR, the current level of evidence to support the use of available therapeutic strategies, and the emergence of tailored drugs now being evaluated in systematic clinical trials. We searched PubMed, Clinicaltrials.gov and Citeline’s Pharmaprojects for pertinent information on emerging anti-rejection strategies, laying a focus on phase II and III trials.
Expert opinion
Currently, we rely on the use of apheresis for alloantibody depletion and intravenous immunoglobulin (referred to as standard of care), preferentially in early active ABMR. Recent systematic trials have questioned the benefits of using the CD20 antibody rituximab or the proteasome inhibitor bortezomib. However, there are now several promising treatment approaches in the pipeline, which are being trialed in phase II and III studies. These include interleukin-6 antagonism, CD38-targeting antibodies, and selective inhibitors of complement. On the basis of the information that has emerged so far, it seems that innovative treatment strategies for clinical use in ABMR may be available within the next 5–10 years.
Funding
This paper was not funded.
Abbreviations
ABMR, antibody-mediated rejection
ATG, antithymocyte globulin
C1-INH, C1 esterase inhibitor
CyA, cyclosporin A
CYP, cytochrome P450
DGF, delayed graft function
DSA, donor-specific antibody
eGFR, estimated glomerular filtration rate
EMA, European Medicines Agency
FcγRIIIA, Fc-gamma receptor IIIA
FDA, Food and Drug Administration
HLA, human leukocyte antigen
IL-6, interleukin-6
IL-6R, interleukin-6 receptor
IVIG, intravenous immunoglobulin
KDIGO, Kidney Disease: Improving Global Outcomes
NK cell, natural killer cell
SOC, standard of care
Notes
1. In the pdf version, there is some re-formatting of Table 1 necessary: There seems to be (e.g. in the row B cells/Rtuximab) a shift of the lines. In the column Status of development, the text for each study should be in a line (e.g. Phase II (prematurely terminated)), so that the associated trial acronyms, identifiers and citations are correctly affiliated.