Projects / Programmes
Combination of medium cut-off dialyzer membrane and diet modification to alleviate residual uremic syndrome of dialysis patients
| Code |
Science |
Field |
Subfield |
| 3.06.00 |
Medical sciences |
Cardiovascular system |
|
| Code |
Science |
Field |
| B560 |
Biomedical sciences |
Urology, nephrology |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
end-stage renal disease, hemodialysis, uremic syndrome, inflammation
Researchers (18)
Organisations (1)
Abstract
Current treatment of end-stage renal failure with hemodialysis is currently insufficient as it fails to effectively remove medium-sized and protein-bound uraemic toxins. The consequence is the persistence of residual uremic syndrome, which includes increased levels of inflammation, increased morbidity and mortality of dialysis patients. Our purpose is to investigate the impact of the simultaneous use of a new dialysis membrane with higher permeability for medium and protein bound uraemic toxins (medium cut-off dialysis membrane) combined with diet modification to reduce the level of inflammation and representative uremic toxins in chronic dialysis patients. We hypothesized that the use of a medium-cut off dialysis membrane and dietary modification work synergistically and cause a significant and clinically meaningful reduction in inflammation and uremic toxin levels compared to on-line hemodiafiltration with a high-flux dialysis membrane. The secondary objective of the study is to determine the efficacy, safety and biocompatibility of regional citrate anticoagulation in dialysis with a medium-cut off dialysis membrane compared to standard heparin anticoagulation.
We designed this study as a prospective, randomized, cross-sectional, interventional, open comparison of dialysis with a medium-cut off membrane and on-line hemodiafiltration. Each patient will be randomly assigned to one of the two treatment sequences: (sequence A) 4 weeks dialysis with a medium cut-off membrane, followed by 4 weeks dialysis with a medium cut-off membrane and increased fiber intake, followed by 4 weeks of haemodiafiltration with a high-flux membrane and 4 weeks hemodiafiltration with a high-flux membrane and increased intake of fiber. (Sequence B) - 4 weeks of high-flux membrane haemodiafiltration and 4 weeks of high-flux membrane haemodiafiltration and increased fiber intake followed by 4 weeks of dialysis with a medium cut-off membrane and then 4 weeks of dialysis with a medium-cut off membrane and increased fiber intake. The main outcome of the study is the concentration of inflammatory mediator interleukin-6. The secondary outcomes of the study are the expression of inflammatory mRNA in peripheral blood monocytes, the serum level of selected representative medium-sized uremic toxins (beta 2-microglobulin, interleukin-8, light chains kappa and lambda, TNF-alpha, advanced glycation end-products) and a level of representative protein-bound toxins of indoxyl sulphate, p-cresol sulphate and trimethylamine-N-oxide.
In order to meet the secondary objective of the study, we will compare the effectiveness of regional citrate anticoagulation with heparin anticoagulation and the parameters of biocompatibility on the medium cut-off membrane. We have hypothesized that regional citrate anticoagulation used on a medium cut-off membrane is equally effective in providing anticoagulation and better in ensuring biocompatibility of blood contact with the dialysis membrane than standard heparin anticoagulation. The main results of this part of the study will be the measurement of the formation of thrombin antithrombin III and D-dimer complexes, the measurement of activation of the complement system by determining the C5a fragment, the measurement of platelet activation and leukocytes by determining platelet factor 4 and myeloperoxidase.
Confirmation of our hypotheses will allow clinical introduction of the dialysis regime which to the largest extent known reduces residual uremic syndrome and will potentially represent the treatment of choice for patients with uremic serositis (e.g. pericarditis), uremic cachexia, recurrent cardiovascular events on dialysis, recurrent infections and chronically elevated inflammatory mediators in the uremia. An analysis of regional citrate anticoagulation will allow the use of a medium cut-off membrane in patients with a bleeding tendency.
Significance for science
Confirmation of our hypotheses will allow clinical introduction of the dialysis regime which to the largest extent known reduces residual uremic syndrome and will potentially represent the treatment of choice for patients with uremic serositis (e.g. pericarditis), uremic cachexia, recurrent cardiovascular events on dialysis, recurrent infections and chronically elevated inflammatory mediators in the uremia. An analysis of regional citrate anticoagulation will allow the use of a medium cut-off membrane in patients with a bleeding tendency.
These findings will have immediate impact on current clinical practice.
Significance for the country
The lessons learned from the implementation of the project will enable us to establish a new strategy of hemodialysis treatment, which will potentially represent the most effective dialysis treatment of residual uraemic syndrome. With this, the main tertiary hospital in Slovenia can be further established as a reference nephrological center in the region and also potentially of increased relevance to domestic and foreign self-paying clients of health services.
