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Endotoxin, Neutrophil Function and Albumin in Renal Insufficiency

NCT01362569 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 239

Last updated 2017-10-11

No results posted yet for this study

Summary

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

Conditions

  • Chronic Renal Insufficiency
  • Acute Renal Failure

Sponsors & Collaborators

  • Austrian Science Fund (FWF)

    collaborator OTHER

  • Vanessa Stadlbauer-Koellner, MD

    lead OTHER

Principal Investigators

  • Vanessa Stadlbauer, MD · Medical Univeristy of Graz

Eligibility

Min Age
18 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2011-07-31
Primary Completion
2014-01-31
Completion
2015-12-31

Countries

  • Austria

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01362569 on ClinicalTrials.gov