Endotoxin, Neutrophil Function and Albumin in Renal Insufficiency (ENARI)
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|ClinicalTrials.gov Identifier: NCT01362569|
Recruitment Status : Completed
First Posted : May 30, 2011
Last Update Posted : October 11, 2017
Chronic kidney disease is widespread in the western world with bacterial infection and sepsis as common complication. It has been shown that innate immune defence, represented by dysfunction of neutrophil granulocytes, is impaired in chronic kidney disease. Another impact of chronic kidney disease on innate immunity is the chronic activation of neutrophils leading to high levels of inflammatory cytokines, thus contributing to protein oxidation. Oxidation of human serum albumin (HSA), the major plasma protein, occurs in chronic kidney disease and leads to further activation of neutrophils. Another important impact of HSA oxidation is the decrease of its binding capacity leading to impaired detoxification ability of albumin. This includes reduced clearance of endotoxin, a major component of the gram negative bacterial cell wall. Circulating endotoxin is recognized by complex formation with lipopolysaccharide binding protein (LBP) followed by binding to CD14 and toll-like receptor (TLR) 4. High systemic endotoxin levels occur in chronic kidney disease and may be the result of decreased clearance ability of HSA and increased gut permeability in combination with intestinal bacterial overgrowth. High systemic endotoxin is associated with worse outcome in several diseases and could be used as predictor for mortality in chronic kidney disease patients.
Endotoxemia in renal insufficiency leads to impaired neutrophil function and to increased albumin oxidation. Oxidized albumin is not able to bind endotoxin adequately any more, which leads to a further increase in oxidative stress and neutrophil dysfunction, resulting in a vicious cycle.
195 patients with renal dysfunction will be enrolled and divided into 5 groups. Additionally, samples of 25 age and sex-matched healthy controls will be collected.
This concept will change the understanding of several aspects of chronic kidney disease and will potentially help to stratify patients into different groups at risk according to their endotoxin status, and their immune and albumin dysfunction. The results of this study will have important implications into the development of novel therapeutic strategies
|Condition or disease|
|Chronic Renal Insufficiency Acute Renal Failure|
|Study Type :||Observational|
|Actual Enrollment :||239 participants|
|Official Title:||Endotoxin, Neutrophil Function and Albumin in Renal Insufficiency|
|Study Start Date :||July 2011|
|Actual Primary Completion Date :||January 2014|
|Actual Study Completion Date :||December 2015|
predialytic renal insufficiency
Patents without renal replacement therapy
patients undergoing regular hemodialysis/hemofiltration
peritoneal dialysis patients
patients undergoing peritoneal dialysis
acute renal failure
patients with acute renal failure
post renal transplantation
patients after renal transplantation
- Endotoxin levels (EU/ml and qualitative positive/negative) [ Time Frame: Day 0 ]Percentage of patients with measurable endotoxin serum levels in each group.
- albumin oxidation (%), albumin binding capacity (ratio), neutrophil function (%), [ Time Frame: Day 0 ]
We want to investigate the following in patients with different stages of chronic renal insufficiency.
Albumin oxidation and function in correlation with the endotoxin status Endotoxin binding to albumin Neutrophil function, energy status and NO metabolism in correlation with the endotoxin status
- microbiome composition [ Time Frame: Day 0 ]In a subgroup of patients undergoing hemodialysis or peritoneal dialysis we will assess the composition of the gut micro biome in stool samples by 16s rDNA sequencing
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01362569
|Department of Internal Medicine|
|Graz, Austria, 8036|
|Principal Investigator:||Vanessa Stadlbauer, MD||Medical Univeristy of Graz|