End-Stage Renal Disease (ESRD)
Conditions
Keywords
End-Stage Renal Disease (ESRD), chronic Inflammation, EPO Resistance, ESA Resistance, high cut-off dialysis, hemodialysis
Brief summary
Chronic inflammation in dialysis patients is linked to cardiovascular mortality and clinical signs and symptoms, like the impaired response to erythropoiesis-stimulating agents (ESAs). This study aims to demonstrate that high cut-off hemodialysis is effective in reducing chronic inflammation and thereby improving response to ESAs.
Detailed description
Chronic inflammation in hemodialysis patients (micro-inflammation) is caused by multiple inflammatory stimuli and becomes apparent by elevated levels of biochemical markers such as CRP, IL-6, cellular activation markers etc. Chronic inflammation is linked to clinical signs and symptoms and cardiovascular mortality in dialysis patients. Inflamed dialysis patients show impaired response to erythropoiesis-stimulating agents (ESA) related to reduced iron utilization (functional iron deficiency) and elevated CRP levels are associated with a greater need for ESA to meet hemoglobin targets. If absolute iron deficiency can been excluded, EPO resistance is likely related to 'inflammatory block'. The high molecular permeability of the Theralite high cut-off membrane allows for significant clearance of cytokines and other pro-inflammatory solutes by hemodialysis as shown in previous trials with high cut-off dialyzers. The study therefore aims to demonstrate that Theralite dialysis is effective in reducing chronic inflammation in ESRD patients, thereby improving EPO responsiveness. If this can be demonstrated, application of Theralite hemodialysis may reduce morbidity and mortality in the long term in ESRD patients.
Interventions
DEVICETheralite (high cut-off hemodialysis)
Hemodialysis with Theralite dialyzer alternating with standard high-flux dialyzer
Sponsors
Gambro Dialysatoren GmbH
Baxter Healthcare Corporation
Vantive Health LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ESRD treated with chronic HD for at least 3 months * Treatment with high-flux dialyzers for at least 3 months * Age ≥18 years * Receiving ESA to treat anemia for at least 3 months * Impaired ESA responsiveness as indicated by EPO resistance index \> median of patients in study center * Transferrin saturation (TSAT) ≥20% (last routine value prior to randomization) * Serum ferritin ≥100 ng/ml (last routine value prior to randomization)
Exclusion criteria
* Acute infection ≤4 weeks prior to randomization * HIV or hepatitis infection * Catheter * Chronic liver disease * Active cancer * Known blood dyscrasia (paraprotein abnormalities) * Known bleeding disorders * Bleeding episode ≤12 weeks prior to randomization * Blood/red cell transfusion ≤12 weeks prior to randomization * Hypoalbuminemia defined as serum albumin concentration below 35 g/L (last routine value prior to randomization) * Participation in another clinical interventional investigation * Pregnancy * Inability to give informed consent * Planned transplantation within study period +3 months * Planned interventions requiring hospitalization \>1 week
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Erythropoietin (EPO) resistance index | 12 weeks after randomization | Weekly EPO dose in international units (IU) per kg body weight divided by hemoglobin value in g/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| high sensitivity C-reactive protein (CRP), hepcidin, Free Light Chains (FLC), Interleukin (IL)-6, Interleukin (IL)-10 | baseline, 4, 8 and 12 weeks | Change in pre-dialysis concentration over study period |
| Urea, Hepcidin, Free Light Chains, IL-6, IL-10 | baseline, week 1 | Pre- and post-dialysis concentration of urea, hepcidin |
| Albumin | baseline, weeks 2,4,6,8,10,12,14,16,18,20,22,24 | Pre-dialysis albumin concentration during study period and follow-up |
Countries
Italy
Outcome results
None listed