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Dialysis related amyloidosis: a disease of chronic retention and inflammation?
J Floege1, J Schäffer, K M Koch
1Division of Nephrology, Medizinische Hochschule Hannover, Germany.
Abstract:
Dialysis related amyloidosis (DRA) has become a major complication of long-term therapy in chronic hemodialysis or peritoneal dialysis patients. DRA is characterized by the presence of beta 2-microglobulin (beta 2m) in the amyloid fibrils. The pathogenesis of DRA is incompletely understood, but most likely is based on the uremic retention of beta 2m. In contrast, current evidence does not favor a significant role of an enhanced beta 2m synthesis rate in uremic patients. Apart from the beta 2m retention, posttranslational modification of the molecule also seems to be an important step in the amyloidogenesis, since, in addition to intact beta 2m, fragmented beta 2m or beta 2, with altered isoelectric properties can be detected in the DRA fibrils. The occurrence of these beta 2m species could be linked to a chronic intermittent stimulation of monokine release or other subclinical inflammatory processes during renal replacement therapy. Thus, it is possible that, as a consequence of repeated cellular activation, protease release and/or intracellular processing of beta 2m occurs. Renal transplantation has been shown to arrest the further progression of DRA. However, since transplantation is not feasible for a significant number of patients, non-transplant strategies to prevent DRA also need to be evaluated. Some, but not all, retrospective studies on DRA associated symptomatology in patients on chronic hemodialysis with high flux membranes have suggested a lesser prevalence in these patients as compared to patients treated with standard cellulosic membranes. To further clarify this issue and to test whether non-transplant therapies indeed may play a role in the prevention of DRA, prospective studies will be needed.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Dialysis Related Amyloidosis (DRA) is a complication of long-term dialysis, caused by beta 2-microglobulin (beta 2m) buildup. Renal transplantation can halt DRA, but non-transplant strategies require further investigation.
Area of Science:
- Nephrology
- Biochemistry
- Pathology
Background:
- Dialysis Related Amyloidosis (DRA) is a significant complication in patients undergoing long-term hemodialysis or peritoneal dialysis.
- DRA is characterized by the accumulation of beta 2-microglobulin (beta 2m) in amyloid fibrils.
- The exact pathogenesis of DRA is not fully understood but is primarily linked to the retention of beta 2m in uremia.
Purpose of the Study:
- To explore the pathogenesis of beta 2m retention and posttranslational modification in Dialysis Related Amyloidosis.
- To evaluate the potential of renal transplantation in arresting DRA progression.
- To investigate non-transplant strategies, including the role of high-flux membranes, in preventing DRA.
Main Methods:
- Analysis of beta 2-microglobulin (beta 2m) species in amyloid fibrils of patients with Dialysis Related Amyloidosis (DRA).
- Review of evidence regarding beta 2m synthesis rates in uremic patients.
- Examination of retrospective studies comparing DRA prevalence in patients using high-flux versus standard cellulosic membranes.
Main Results:
- Beta 2-microglobulin (beta 2m) retention is the likely cause of Dialysis Related Amyloidosis (DRA), not increased synthesis.
- Posttranslational modifications of beta 2m, including fragmentation and altered isoelectric properties, contribute to amyloidogenesis.
- Retrospective studies suggest a potentially lower prevalence of DRA with high-flux dialysis membranes compared to standard ones.
Conclusions:
- Renal transplantation can stop the progression of Dialysis Related Amyloidosis (DRA).
- Non-transplant strategies, such as the use of high-flux membranes, may play a role in preventing DRA, but require prospective validation.
- Further prospective studies are needed to confirm the efficacy of non-transplant therapies in preventing DRA.