Removal of Ligand-bound Iron During Intravenous (IV) Iron Administration in Hemodialysis (HD)

Study Overview
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Brief Summary
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The study's hypothesis is that HD with large pore dialyzers remove to the dialysate iron which is bound to potentially dialyzable ligands, after it's release from intravenous iron compound administered during hemodialysis.

Detailed Description
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Most hemodialysis(HD) patients receive during HD intravenous iron compounds, which are composed of an iron core and a sugar polymer shell. A small percentage of iron from the iron compound is released to the plasma, and may be associated with increased oxidative stress and protein oxidation. The study's hypothesis is that HD with large pore dialyzers may remove to the dialysate iron which is bound to potentially dialyzable ligands, after it's release from intravenous iron compound administered during hemodialysis. Ligand-bound iron removal is also hypothesized to be affected by dialysate calcium and bicarbonate concentrations, which may affect iron-ligand binding. Study Specific aims are: To evaluate Iron removal assessing dialysate iron levels. Effect of iron removal and it's associated experimental conditions on patient status, assessing plasma AOPP levels and inflammation related parameters Study include 3 parts Comparing large to small pore dialyzers (To achieve baseline uniform conditions, patients will be on uniform dialysate bicarbonate and calcium concentrations of 33 mEq/L and 3 mEq/L,respectively, using large pore dialyzers during this part, besides the 2 HD sessions evaluating low pore dialyzers) and after few week break Using large pore dialyzers to compare Low to high dialysate bicarbonate concentration (using uniform dialysate calcium concentrations of 3 mEq/L) and after few week break Low to high dialysate calcium concentrations concentration (using uniform dialysate bicarbonate of 33 mEq/L) In each part, patients will be first evaluated in HD without IV iron administration, which will serve as a control for evaluation after a week in HD with IV iron administration. In each part, patients will be randomized to start either with one of the 2 experimental conditions, and after 1 week without evaluation will cross-over to the other experimental condition. Patients may participate in 1,2 or the 3 parts of study depending on their will and condition.

Official Title
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Removal of Ligand-bound Iron During Intravenous Iron Administration in Hemodialysis by Large Pore Dialyzers

Conditions
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Hemodialysis Patients

Intervention / Treatment
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* Device: large pore (FX80) compared to small pore dialyzer (F8HPS)
* Other: Dialysate bicarbonate of 33 mEq/L compared to 40 mEq/L
* Other: Dialysate calcium of 3 mEq/L compared to 2.5 mEq/L


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hemodialysis patients Exclusion Criteria: Acute disease (infection, thrombosis, ischemia, bleeding) Hepatitis B, Hepatitis C or HIV Intravenous iron administration or packed red cell transfusion in the last 3 weeks prior to the study Refusal to comply with limitations in fat containing food during HD with plasma sampling for AOPP evaluation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 88 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>large pore dialyzers (FX80, Fresenius, Germany) | Device: large pore (FX80) compared to small pore dialyzer (F8HPS)<br>* Effect of pore size<br>|
| Experimental: 2<br>small pore dialyzers ( F8HPS, Fresenius, Germany) | Device: large pore (FX80) compared to small pore dialyzer (F8HPS)<br>* Effect of pore size<br>|
| Experimental: A<br>dialysate bicarbonate concentration of 33 mEq/l | Other: Dialysate bicarbonate of 33 mEq/L compared to 40 mEq/L<br>* Effect of dialysate bicarbonate concentration<br>|
| Experimental: B<br>dialysate bicarbonate concentration of 40 mEq/l | Other: Dialysate bicarbonate of 33 mEq/L compared to 40 mEq/L<br>* Effect of dialysate bicarbonate concentration<br>|
| Experimental: I<br>dialysate calcium concentration of 3 mEq/L | Other: Dialysate calcium of 3 mEq/L compared to 2.5 mEq/L<br>* Effect of dialysate calcium concentration<br>|
| Experimental: II<br>dialysate calcium concentration of 2.5 mEq/L | Other: Dialysate calcium of 3 mEq/L compared to 2.5 mEq/L<br>* Effect of dialysate calcium concentration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Dialysate Iron levels 2. Plasma levels of advanced oxidation protein products(AOPP) |  | Before HD, after 1 hour of HD with or without IV iron and at end of HD | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemodialysis, iron, inflammation, atomic absorption, dialysate, advanced oxidation protein products, large pore dialysate, bicarbonate, calcium, citrate, ligand