Chronic Rejection After Kidney Transplantation.
A review of how long-term rejection damages transplanted kidneys, highlighting the central role of natural killer cells in microvascular inflammation and the promise of newer antibody treatments such as felzartamab.
Background
In kidney transplantation, ongoing alloimmune processes — commonly triggered by HLA incompatibilities — can drive chronic rejection affecting the microcirculation and the tubulointerstitium. Continuous inflammation may cause progressive, irreversible graft injury, culminating in graft dysfunction and accelerated transplant failure. Antibody-mediated rejection is the most extensively studied variant.
Key findings
Experimental and translational work has delineated a complex interplay of immune mechanisms driving rejection. In microvascular inflammation, a hallmark lesion of antibody-mediated rejection, natural killer cells have emerged as pivotal effector cells; this role is supported by immunohistologic evidence, bulk and spatial transcriptomics, and functional genetics. Despite substantial research effort, a major unmet need for approved rejection therapies persists, with many trials yielding negative outcomes.
Clinical implications
Several therapies are under investigation, notably felzartamab, a monoclonal antibody targeting CD38 — highly expressed on natural killer cells and antibody-producing plasma cells. In an exploratory phase 2 trial in late antibody-mediated rejection it showed potential to resolve molecular and morphologic rejection activity and injury, predominantly by targeting NK cell effector function. The review emphasises that pivotal trials focused specifically on chronic transplant rejection are still required before practice changes.
Category
Transplant
Source
Transplantation
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