Chronic Renal InsufficiencyENARINCT01362569
Endotoxin, Neutrophil Function and Albumin in Renal Insufficiency
An observational study of Chronic Renal Insufficiency and Acute Renal Failure, run by Vanessa Stadlbauer-Koellner, MD at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Renal Insufficiency, Acute Renal Failure
- How many people
- 239 participants
- Where
- 1 siteAustria
- Study dates
- Jul 2011to Dec 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 1. 50 predialytic patients (a) 25 patients with an eGFR between 30 and 45 (KDIGO 3B) and (b) 25 patients with an eGFR between 15 and 30 (KDIGO 4) 2. 50 patients undergoing hemodialysis or hemodiafiltration for ESRD (a) 25 patients under therapy with sevelamer and (b) 25 patients without sevelamer 3. (a) 25 patients undergoing peritoneal dialysis for ESRD without signs of infection and (b) 25 patients undergoing peritoneal dialysis for ESRD with peritonitis 4. 25 patients with acute renal failure 5. 45 patients after kidney transplantation (a) 15 patients with an eGFR > 45, (b) 15 patients with an eGFR between 30 and 45 and (c) 15 patients with an eGFR < 30 6. 25 age and sex-matched healthy controls
Who may be able to join
- Age between 18-80 years, informed consent Groups 1a, 1b, 2a, 2b, 3a, 3b Patients with chronic kidney disease as defined previously [65] either
- 1a) with an eGFR between 30 and 45 (KDIGO 3B)
- b) with an eGFR between 15 and 30 (KDIGO 4)
- a) undergoing hemodialysis for ESRD
- 2b) undergoing hemodiafiltration for ESRD
- 3a) undergoing peritoneal dialysis for ESRD without signs of infection
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- 3b) undergoing peritoneal dialysis for ESRD with peritonitis ≥2 out of the 4 criteria (>100 leucocytes/50%neutrophils, cloudy peritoneal dialysate, typical clinical presentation with fever and abdominal pain, positive culture from the peritoneal dialysate)
- Group 4 Patients with acute kidney injury (AKIN 3 [66] defined as an increase in serum creatinine to 300% (3-fold) from baseline or serum creatinine 4.0 mg/dl with an acute rise of at least 0.5mg/dl or urine output of < 0.3ml/kg/h 24h or anuria 12h) Initiation of acute renal replacement therapy
- Group 5 Stable patients after kidney transplantation with either an eGFR > 45, between 30 and 45 or < 30
- Group 6: Healthy controls
Who cannot join
- Malignancy, pregnancy,chronic inflammatory bowel disease, celiac disease, active alcohol abuse, any severe organ dysfunction unrelated to renal dysfunction Groups 1a, 1b, 2a, 2b, 3 Organ transplantation Clinical evidence of active infection (except for group 3b) Treatment with antibiotics within the last 2 weeks (except for group 3b)
- Group 4 Preexisting ESRD
- Group 5 Clinical evidence of active infection Treatment with antibiotics within the last 2 weeks
- Group 6:
- Any evidence of acute or chronic disease
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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
Read the detailed description
Laboratory methods Endotoxin will be detected by an adapted limulus amoebocyte lysate assay. LBP and sCD14 will be determined by means of ELISA. HPLC will be used to determine nitrate, nitrite, albumin fractions, albumin binding capacity, iNOS expression and energy status of neutrophils. For investigation of oxidation driven by leukocyte derived myeloperoxidase, mass spectrometry analysis will be used. Carbonyl contents of proteins will be detected by ELISA. Neutrophil function and TLR2, 4 and 9 expression will be studied by flow cytometrical analysis. For cell culture tests, freshly isolated neutrophils or differentiated HL60 cells will be used and incubated with albumin and/or endotoxin. Stool samples will be used for 16srDNA sequencing of the gut microbiome.
- Conditions
- Chronic Renal Insufficiency, Acute Renal Failure
- Keywords
- endotoxin, neutrophil function, albumin function
- Medical subject headings
- Renal Insufficiency, Chronic, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| predialytic renal insufficiency | Patents without renal replacement therapy | |
| hemodialysis/hemofiltration patients | 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 | |
| healthy controls | control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endotoxin levels (EU/ml and qualitative positive/negative)
Percentage of patients with measurable endotoxin serum levels in each group.
Measured: Day 0
Secondary outcomes (2)
albumin oxidation (%), albumin binding capacity (ratio), neutrophil function (%),
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
Measured: Day 0
microbiome composition
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
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2011 (estimated)
- Study startJul 2011
- Primary completionJan 2014
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Renal InsufficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 239 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanessa Stadlbauer-Koellner, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Austrian Science Fund (FWF)
- Responsible party
- Sponsor-investigator, Vanessa Stadlbauer-Koellner, MD, Medical University of Graz
- Investigators
- Vanessa Stadlbauer, MD, Principal investigator, Medical Univeristy of Graz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01362569
- Sponsor's protocol ID
- P23532
- Acronym
- ENARI
- Status last verified
- Oct 2017
- First submitted
- 23 May 2011
- Last updated
- 11 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endotoxin, Neutrophil Function and Albumin in Renal Insufficiency
- ClinicalTrials.gov ID
- NCT01362569
- Acronym / sponsor ID
- ENARI / P23532
- Conditions
- Chronic Renal Insufficiency, Acute Renal Failure
- Keywords
- endotoxin, neutrophil function, albumin function
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 239 participants (actual)
- Lead sponsor
- Vanessa Stadlbauer-Koellner, MDUniversity, hospital or other
- Collaborators
- Austrian Science Fund (FWF)
- Study start
- Jul 2011
- Primary completion
- Jan 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 30 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Laboratory methods Endotoxin will be detected by an adapted limulus amoebocyte lysate assay. LBP and sCD14 will be determined by means of ELISA. HPLC will be used to determine nitrate, nitrite, albumin fractions, albumin binding capacity, iNOS expression and energy status of neutrophils. For investigation of oxidation driven by leukocyte derived myeloperoxidase, mass spectrometry analysis will be used. Carbonyl contents of proteins will be detected by ELISA. Neutrophil function and TLR2, 4 and 9 expression will be studied by flow cytometrical analysis. For cell culture tests, freshly isolated neutrophils or differentiated HL60 cells will be used and incubated with albumin and/or endotoxin. Stool samples will be used for 16srDNA sequencing of the gut microbiome.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| predialytic renal insufficiency | – | –Patents without renal replacement therapy |
| hemodialysis/hemofiltration patients | – | –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 |
| healthy controls | – | –control group |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 1. 50 predialytic patients (a) 25 patients with an eGFR between 30 and 45 (KDIGO 3B) and (b) 25 patients with an eGFR between 15 and 30 (KDIGO 4) 2. 50 patients undergoing hemodialysis or hemodiafiltration for ESRD (a) 25 patients under therapy with sevelamer and (b) 25 patients without sevelamer 3. (a) 25 patients undergoing peritoneal dialysis for ESRD without signs of infection and (b) 25 patients undergoing peritoneal dialysis for ESRD with peritonitis 4. 25 patients with acute renal failure 5. 45 patients after kidney transplantation (a) 15 patients with an eGFR > 45, (b) 15 patients with an eGFR between 30 and 45 and (c) 15 patients with an eGFR < 30 6. 25 age and sex-matched healthy controls
Key inclusion criteria (10 listed)
- Age between 18-80 years, informed consent Groups 1a, 1b, 2a, 2b, 3a, 3b Patients with chronic kidney disease as defined previously [65] either
- 1a) with an eGFR between 30 and 45 (KDIGO 3B)
- b) with an eGFR between 15 and 30 (KDIGO 4)
- a) undergoing hemodialysis for ESRD
- 2b) undergoing hemodiafiltration for ESRD
Key exclusion criteria (5 listed)
- Malignancy, pregnancy,chronic inflammatory bowel disease, celiac disease, active alcohol abuse, any severe organ dysfunction unrelated to renal dysfunction Groups 1a, 1b, 2a, 2b, 3 Organ transplantation Clinical evidence of active infection (except for group 3b) Treatment with antibiotics within the last 2 weeks (except for group 3b)
- Group 4 Preexisting ESRD
- Group 5 Clinical evidence of active infection Treatment with antibiotics within the last 2 weeks
- Any evidence of acute or chronic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Endotoxin levels (EU/ml and qualitative positive/negative)
Time frame: Day 0
Percentage of patients with measurable endotoxin serum levels in each group.
2 secondary outcomes
albumin oxidation (%), albumin binding capacity (ratio), neutrophil function (%),
Time frame: Day 0
microbiome composition
Time frame: Day 0
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vanessa Stadlbauer, MD principal investigator
Medical Univeristy of Graz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Renal Insufficiency and Acute Renal Failure, run by Vanessa Stadlbauer-Koellner, MD at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endotoxin levels (EU/ml and qualitative positive/negative) (time frame: Day 0). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2017.