Dialysis-related Amyloidosis: Is It Gone or Should It Be?
Laura Labriola1, Michel Jadoul1
1Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
Abstract:
The prevalence and severity of dialysis-related amyloidosis (DRA) appear to have decreased significantly over the last two decades, although recent, large-scale epidemiological studies show that DRA continues to occur. Recent experimental findings have documented a direct cellular toxicity of β2microglobulin (β2m) fibrils but the mechanisms of β2m fibrillogenesis remain incompletely understood. Although a high plasma concentration of β2m is still considered as a prerequisite for developing DRA, other factors have been clearly incriminated such as older age at dialysis onset and longer dialysis vintage, or suspected effects such as proinflammatory effects of bioincompatible dialysis techniques. Improved dialysis technology has definitely played a role in delaying the onset of the disease, although the respective contributions of high-flux biocompatible membranes, use of convective mode, and ultrapure dialysate remain imperfectly defined. Importantly, DRA still does exist and no current dialytic modality seems able to fully prevent it. Awaiting further progress in the understanding of DRA pathogenesis, the use of biocompatible high-flux membranes and ultrapure dialysate is strongly recommended in order to minimize or delay its onset. Convective regimens may provide an additional benefit.
Insights
Dialysis-related amyloidosis (DRA) is decreasing but still occurs, linked to beta2-microglobulin (β2m) fibrils. Advanced dialysis techniques may delay onset, but cannot fully prevent this condition.
Area of Science:
- Nephrology
- Biomaterials Science
- Clinical Epidemiology
Background:
- Dialysis-related amyloidosis (DRA) prevalence has declined but persists, with ongoing research into beta2-microglobulin (β2m) fibril toxicity.
- High plasma β2m levels are a prerequisite for DRA, with age and dialysis vintage as contributing factors.
- The precise mechanisms of β2m fibrillogenesis and cellular toxicity require further elucidation.
Discussion:
- Improved dialysis technologies, including high-flux biocompatible membranes, convective therapies, and ultrapure dialysate, have contributed to delaying DRA onset.
- The specific impact of each technological advancement on DRA prevention remains incompletely defined.
- Despite advancements, no current dialysis modality completely prevents DRA, highlighting the need for continued research.
Key Insights:
- Beta2-microglobulin (β2m) fibrils exhibit direct cellular toxicity, though fibrillogenesis mechanisms are not fully understood.
- Older age at dialysis initiation and longer dialysis vintage are implicated in DRA development.
- While improved dialysis technology mitigates DRA, it does not offer complete prevention.
Outlook:
- Further research into DRA pathogenesis is crucial for developing more effective prevention strategies.
- Biocompatible high-flux membranes and ultrapure dialysate are recommended to minimize or delay DRA onset.
- Convective dialysis regimens may offer additional benefits in managing or preventing DRA.
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