Dialysis Membrane Reaction Clinical Trial
— DIALOMICOfficial title:
Characterization of Proteins and Forms of Albumin Removal Capacities of the Theranova Membrane by Innovating Proteomic Investigations
Hemodialysis is the major technique of renal suppleance and membrane improvements allow an
efficient depuration. During the past fifty years, improving the architecture of the
membranes increased constantly the clearance of uremic toxins. Online-hemodiafiltration
allowed a potential interest for decreasing morbi-mortality, but this technique is not
available in all hemodialysis centers yet. Theranova membrane, by its innovating
architecture, could be a valuable option for the enhancement of toxin removal in patients
who are not eligible for online-hemodiafiltration techniques. Interestingly, many works
pointed adsorptive capacities of dialysis membranes and these observations suggest that
adsorption cannot be considered as an epiphenomenon. However, there is a lack of knowledge
about the extent of its benefits in hemodialysis. The efficiency of a session of
hemodialysis is routinely based on the clearance of only few generic toxins (urea,
ß2-microglobulin, myoglobin). The eKT/V formula permitted to link a good depuration of urea
with a better survival. EuTox described in a recent review, a large panel of middle
molecules considered as uremic toxins. As there are many involved toxins, modern evaluation
of hemodialysis efficiency can't be still based on the only description of ß2-microglobulin
and urea removals. Inflammation status is routinely measured with blood levels of CRP.
However, its accumulation is not leading to a toxicity. Many others inflammatory markers
have been linked with morbidity and atherosclerosis, the main cause of mortality in ESRD
patients. Obviously, removal of inflammatory markers by different dialyzers needs to be
assess concomitantly but single conventional dosages are time-consuming.
A minimal albumin loss is considered as another important factor for a safe hemodialysis.
Due to its multiple biological functions, albumin may be one of the most important protein
for the maintenance of body homeostasis. Recent works were interested in the potential
toxicity of some isoforms of the albumin and especially in chronic kidney disease. Modified
forms of albumin have been linked with toxic properties and the removal of modified forms
could be beneficial. Furthermore, albumin oxidation can lead to an under-estimation of
albumin levels with the routinely used assay. A modern evaluation of the capacities of
depuration of dialyzers clearly needs to integrate the evaluation of the clearance and
generation of modified forms of albumin and proteins.
Proteomic techniques allow an interesting non-selective integrative approach. This
exhaustive view would be particularly adequate for building a snapshot of blood uremic
toxins, permeative and adsorptive capacities of each membrane. Due to a high sensitiveness,
proteomic techniques can improve dramatically the characterization of the depuration
capacities of different hemodialysis membranes considering a large range of uremic toxins
especially with middle molecular weight, a large panel of inflammatory markers and modified
forms of albumin. Furthermore, proteomic approach can help to build a quasi-exhaustive
description of all the proteins removed by a membrane.
This project aims to compare the removal capacities of each membrane on a large range of
proteins and forms of albumin (native and modified) with a highly-sensitive LC-MS/MS
proteomic approach. We will also build the complete proteome of depuration of each tested
membrane.
| Status | Not yet recruiting |
| Enrollment | 20 |
| Est. completion date | April 2018 |
| Est. primary completion date | April 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Age = 18 years old - Patient on hemodialysis for at least 1 year - Patient with a functional vascular access permitting at least 300 mL/min of blood flow. Exclusion Criteria: - Running infection or other active disease (scheduled surgery, cancer, hospitalisation), - Catheter as vascular access, - Recirculation of vascular access over 10%. |
| Country | Name | City | State |
|---|---|---|---|
| France | Service de Néphrologie -Hypertension - Hémodialyse, Hôpital Edouard Herriot | Lyon |
| Lead Sponsor | Collaborator |
|---|---|
| Hospices Civils de Lyon |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Comparison of Theranova and FX1000 in high-flux hemodialysis on whole proteome of depuration (qualitative and semi-quantitative description of all the proteins depurated by absorption and convection) | Semi-quantitative analysis is based on the adondance relative of the protein detected on the spectra from the mass spectrometry assay. Quantity will be extrapoled from the level of B2-microglobulin which will be previously assayed in the original samples. | Proteome is evaluated after an 8-weeks session of use of each membrane | |
| Secondary | Comparison of Theranova, FX1000 in high-flux hemodialysis and FX1000 in online-hemodiafiltration on differential depuration capacities among albumin isoforms, albumin loss in the dialysate and adsorbed onto the membranes | Mass excess will be assayed from each amino acid of albumin peptide. This mass excess will be linked with a specific adduct and percentage of presence of each adduct will be calculated. | Isoforms of albumin are evaluated at week 1 and week 8 of use of each membrane and before and after a hemodialysis session during week 1 | |
| Secondary | Comparison of Theranova and FX1000 in high-flux hemodialysis on quantitative removal of protein-bounded toxins and quantitative distribution of inflammatory markers removed by dialysis. | Protein-bounded toxins: indoxyl sulfate, p-cresyl sulfate, indole-3 acetic acid — liquid chromatography Inflammatory markers : ET-1, RANTES, MIP-1alpha, MIP-1ß, Eotaxin, MCP-1, Fractalkin, IL-1, IL-2, IL-6, IL-8, IL-10, IL-18, TNF-alpha, C5a, C3a, Factor D, sICAM-1, sVCAM-1, sE-selectin, PAI-1, sFlt-1 — Luminex assay | Evaluation after a 8-weeks session of use of each membrane | |
| Secondary | Comparison of eKT/V of urea and ß2-microglobulin, removal rates and amount in the dialysate of ß2-microglobulin and myoglobin. | Evaluation after a 8-weeks session of use of each membrane | ||
| Secondary | Comparison of serum albumin level after 8 weeks of hemodialysis with (Theranova in hemodialysis, FX1000 in online-hemodiafiltration, FX1000 in hemodialysis) | Evaluation after a 8-weeks session of use of each membrane |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Not yet recruiting |
NCT06281028 -
SOLACEA-H in Heparin-sparing Haemodialysis
|
N/A |