Disorder Related to Renal TransplantationCONFUCIUSNCT02515643
Contribution of Renal Function to Endothelial Dysfunction in Living Kidney Donors and Transplant Recipients
An observational study of Disorder Related to Renal Transplantation and Chronic Kidney Disease, run by Hospital Universitari Vall d'Hebron Research Institute at 4 sites in Spain.
Trial summary
Endothelial dysfunction one-year after transplantation mainly depends on transplant-associated factors and only marginally on reduced renal function. OBJETIVES Primary objective Estimate the contribution of renal dysfunction to endothelial dysfunction in two cohorts of patients, living kidney donors and their… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Disorder Related to Renal Transplantation, Chronic Kidney Disease, Endothelial Dysfunction
- What is being tested?
- Endothelial dysfunction
- How many people
- 120 participants
- Where
- 4 sitesSpain
- Study dates
- Jul 2015to Dec 2017
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Cohort 1 Healthy subjects who will undergo a nephrectomy as part of the living donor program at each participating center. Cohort 2 Renal transplant recipients from cohort 1
Who may be able to join
- No history of familiar nephropathies and/other diseases that may increase the risk for renal disease in the future.
- Donor age ≥ 18 years
- Isotopic GFR > 80 ml/min/1.73m2
- Microalbuminuria< 30 mg/g
- Normal urinary sediment
- Normal blood pressure defined as <120/90 mmHg and without other risk factors for cardiovascular disease, and with good/normal kidney function or well-controlled hypertension with one anti-hypertensive drug,
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- No previous history of diabetes including gestational diabetes and fasting glucose < 126 mg/dl and 2h serum glucose after 75 g oral glucose tolerance test < 200 mg/dl
- Signed informed consent
- Chronic kidney disease stage 5
- Negative complement dependent lymphocytotoxicity donor-recipient cross-match.
- Informed signed consent
Who cannot join
- History of cancer except non-melanoma cutaneous neoplasia
- History of vasculitis (e.g. lupus), sarcoidosis, gastrointestinal inflammatory diseases, autoimmune-disease
- History of major cardiovascular events
- History of deep vein thrombosis or pulmonary embolism.
- Active infection including hepatitis B, C and HIV infections.
- Anatomic vascular variants precluding laparoscopic nephrectomy
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- Renal stones except a solitary lithiasis< 1.5 cm once metabolic disorders are ruled out
- Major psychiatric disorders
- Active alcohol, tobacco or drug abuse
- Obesity defined as body mass index > 35 kg/m2.
- Pregnancy
- Glomerulonephritis with high recurrence rate after transplantation (focal segmental glomerulosclerosis and type II membranoproliferative glomerulonephritis)
- Severe aortoiliac atherosclerosis precluding transplantation
- Major psychiatric disorders
- Alcohol and drug abuse
- Active infection
- Patients requiring desensitization treatment before transplantation.
- Pregnancy
Trial locations and contacts
4 sites in 1 country.
Spain4 sites, 4 recruiting
- Recruiting
Hospital del Mar
Barcelona, Barcelona, 08003
Julio Pascual, MD, PhD, +34 932 48 31 62, 99176@parcdesalutmar.cat
Marta Crespo, MD,PhD
- Recruiting
Vall d'Hebron Research Institute
Barcelona, Barcelona, 08035
Francesc Moreso, MD, PhD, +34 93 274 60 79, fjmoreso@vhebron.net
Francesc Moreso, MD, PhD
- Recruiting
Hospital Regional Universitario Carlos Haya
Málaga, Malaga, 29010
Domingo Hernandez, MD, PhD, +34 951 29 11 74, domingohernandez@gmail.com
Mercedes Cabello
- Not yet recruiting
Hospital Universitario Canarias
Santa Cruz de Tenerife, Canary Islands, 38320
Armando Torres, MD, PhD, +34 922 31 93 38, atorres@gmail.com
Ana Gonzalez-Rinne, MD
About this study
Official title: Estimating the Contribution of Renal Function to Endothelial Dysfunction by a Two-cohort Study: Living Kidney Donors and Their Transplant Recipients
Endothelial dysfunction one-year after transplantation mainly depends on transplant-associated factors and only marginally on reduced renal function.
OBJETIVES Primary objective Estimate the contribution of renal dysfunction to endothelial dysfunction in two cohorts of patients, living kidney donors and their transplant recipients.
Read more
Secondary objectives
To evaluate in both cohorts of patients before and after nephrectomy/transplantation the evolution of the following parameters:
- Renal function (iohexolGFR, proteinuria/microalbuminuria).
- Blood pressure (24 h ambulatory blood pressure measurement)
- Surrogate variables of subclinical atherosclerosis (carotid ultrasound, ankle-brachial index, pulse wave velocity).
DESIGN Non-interventional, prospective, multicenter, longitudinal study of two cohorts: living kidney donors and their transplant recipients.
Read the detailed description
HYPOTHESIS
BACKGROUND: Chronic kidney disease (CKD) is associated with endothelial dysfunction, but the link between cardiovascular risk and CKD is difficult to establish because other conditions such as diabetes, hypertension and transplant-related factors are present in these patients. Living donors are healthy individuals that represent a near-ideal experimental model of CKD since they undergo a time-defined reduction of GFR after nephrectomy in the absence of other confounding factors present in patients with mild to moderate CKD.
HYPOTHESIS: Reduction of GFR after donation is associated with increased while renal transplantation is associated with reduced endothelial dysfunction markers.
AIM: To prospectively evaluate biomarkers of endothelial dysfunction and surrogate variables of subclinical atherosclerosis in a cohort of living kidney donors before and one year after donation and in their recipients before and one year after transplantation.
PATIENTS AND METHODS: In two cohorts of 60 living kidney donors (1 month before and 1 year after donation) and in their 60 renal transplant recipients (1 month before and 1 year after transplantation) the following variables will be recorded: iohexol glomerular filtration rate (GFR), proteinuria, microalbuminuria, insulinemia, oral glucose tolerance test, total and LDL/HDL cholesterol, number of carotid plaques and intima-media thickness, carotid-femoral pulse wave velocity, ankle-brachial index, 24-hours ambulatory monitoring of blood pressure. The following biomarkers of endothelial dysfunction and subclinical inflammation will be determined: SVCAM-1, PTX3, ICAM-1, von Willebrand factor, E-selectin, platelet/endothelial cell adhesion molecule (PECAM1), interleukin 6 (IL-6), soluble receptor of tumor necrosis factor (sTNFR1 and sTNFR2), high sensitive C reactive protein (hs-CRP) and soluble TNF-like weak inducer of apoptosis (sTWEAK).
EXPECTED RESULTS. In healthy subjects decrease of renal function after living donation will be associated with increased endothelial dysfunction markers. On the contrary, after transplantation a decrease of endothelial dysfunction markers will be observed. Despite at one year both cohorts of patients will have a similar GFR, the investigators expect that amelioration of endothelial dysfunction in transplants will be higher than worsening of endothelial dysfunction in their donors. Thus, the study of these two cohorts will allow estimating the contribution of renal dysfunction per se and transplant-associated comorbidities to endothelial dysfunction in chronic kidney disease.
- Conditions
- Disorder Related to Renal Transplantation, Chronic Kidney Disease, Endothelial Dysfunction
- Being tested
- Endothelial dysfunction
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endothelial dysfunctionOther
One month before surgery and one year after, the following procedures will be performed in donors and recipients:
- Blood samples will be obtained for the measurement of endothelial dysfunction and low grade inflammation markers.
- Atherosclerotic burden: carotid ultrasound to determine the number of plaques and intima-media thickness, carotid-femoral pulse wave velocity (m/s) will be performed by pulse tonometry.
- Ambulatory blood pressure monitoring with overnight-automated ABPM monitor
- Estimation of glomerular filtration rate by Iohexol method
| Study group | Role | What they receive |
|---|---|---|
| Endothelial dysfunction in Cohort 1 | Assessment of endothelial dysfunction in healthy subjects who will undergo a nephrectomy as part of the living donor program at each participating center. Receives: Other: Endothelial dysfunction | |
| Endothelial dysfunction in Cohort 2 | Assessment of endothelial dysfunction in renal transplant recipients from cohort 1 Receives: Other: Endothelial dysfunction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentual change of sVCAM
Biomarker of endothelial dysfunction: Soluble VCAM (vascular cell adhesion molecule). Determination of serum levels by Luminex. Percentual change between baseline and 1 year levels.
Measured: 1 year
Secondary outcomes (14)
Glomerular filtration rate
Renal function will be estimated before donation by iohexol clearance and expressed as mL/min/1.73 m2 in donors and at 1 year in donors and recipients.
Measured: 1 year
Microalbuminuria
Microalbuminuria (mg/g creatinine) will be determined before donation and at 1 year in donors and at 1 year in transplant recipients.
Measured: 1 year
Blood pressure (24 h ambulatory blood pressure measurement)
Ambulatory blood pressure monitoring (mm Hg) with overnight-automated ABPM monitor (Spacelab 90207; Spacelabs Healthcare,USA) with appropriate cuff sizes for each patient.
Measured: 1 year
Number of carotid plaques and carotid intima-media thickness
Atherosclerotic burden: carotid ultrasound to determine the number of plaques and intima-media thickness will be held in both carotid arteries with a high-frequency (8-12 MHz) linear transducer (ESAOTE, 7300, Florence, Italy),
Measured: 1 year
Pulse wave velocity.
Carotid-femoral pulse wave velocity (m/s) will be measured by pulse tonometry (Sphingmocor Atcor, EM3, Australia).
Measured: 1 year
Percentual change of sICAM
Biomarker of endothelial dysfunction: Soluble ICAM (intercellular adhesion molecule). Determination of serum levels by Luminex. Percentual change between baseline baseline and 1 year levels.
Measured: 1 year
Percentual change of PECAM
Biomarker of endothelial dysfunction: PECAM (platelet/endothelial cell adhesion molecule). Determination of serum levels by Luminex. Percentual change between baseline baseline and 1 year levels.
Measured: 1 year
Percentual change of vWF
Biomarker of endothelial dysfunction: vWF (von Willebrand factor). Determination of serum levels by Luminex. Percentual change between baseline baseline and 1 year levels.
Measured: 1 year
Percentual change of E-selectin
Biomarker of endothelial dysfunction: Soluble E-selectin. Determination of serum levels by Luminex.Percentual change between baseline baseline and 1 year levels.
Measured: 1 year
Percentual change of PTX3
Biomarker of endothelial dysfunction: PTX3 (pentraxin). Determination of serum levels by ELISA. Percentual change between baseline baseline and 1 year levels.
Measured: 1 year
Percentual change of hs-CRP
Biomarker of subclinical inflammation: hs-CRP (high sensitive C reactive protein). Determination of serum levels by nephelometry. Percentual change between baseline baseline and 1 year levels.
Measured: 1 year
Percentual change of IL-6
Biomarker of subclinical inflammation: IL-6 IL-6 (interleukin 6). Determination of serum levels by Luminex. Percentual change between baseline baseline and 1 year levels.
Measured: 1 year
Percentual change of sTNFR1 and sTNFR2
Biomarker of subclinical inflammation: sTNFR1 and sTNFR2 (soluble tumor necrosis factor receptor). Determination of serum levels by Luminex. Percentual change between baseline baseline and 1 year levels.
Measured: 1 year
Percentual change of sTWEAK
Biomarker of subclinical inflammation: sTWEAK (soluble TNF-like weak inducer of apoptosis). Determination of serum levels by ELISA. Percentual change between baseline baseline and 1 year levels.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2015 (estimated)
- Study startJul 2015
- Primary completionDec 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Disorder Related to Renal TransplantationStudies 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
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Teva Pharmaceutical Industries, Ltd.
- Responsible party
- Sponsor
- Investigators
- Francesc Moreso, MD, PhD, Principal investigator, Hospital Vall d'Hebron
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02515643
- Sponsor's protocol ID
- PR(AG)219/2014
- Acronym
- CONFUCIUS
- Status last verified
- Mar 2017
- First submitted
- 10 Jul 2015
- Last updated
- 28 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Estimating the Contribution of Renal Function to Endothelial Dysfunction by a Two-cohort Study: Living Kidney Donors and Their Transplant Recipients
- ClinicalTrials.gov ID
- NCT02515643
- Acronym / sponsor ID
- CONFUCIUS / PR(AG)219/2014
- Conditions
- Disorder Related to Renal Transplantation, Chronic Kidney Disease, Endothelial Dysfunction
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research InstituteUniversity, hospital or other
- Collaborators
- Teva Pharmaceutical Industries, Ltd.
- Study start
- Jul 2015
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 5 Aug 2015 (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.
Endothelial dysfunction one-year after transplantation mainly depends on transplant-associated factors and only marginally on reduced renal function.
OBJETIVES Primary objective Estimate the contribution of renal dysfunction to endothelial dysfunction in two cohorts of patients, living kidney donors and their transplant recipients.
Secondary objectives
To evaluate in both cohorts of patients before and after nephrectomy/transplantation the evolution of the following parameters:
- Renal function (iohexolGFR, proteinuria/microalbuminuria).
- Blood pressure (24 h ambulatory blood pressure measurement)
- Surrogate variables of subclinical atherosclerosis (carotid ultrasound, ankle-brachial index, pulse wave velocity).
DESIGN Non-interventional, prospective, multicenter, longitudinal study of two cohorts: living kidney donors and their transplant recipients.
Detailed description
HYPOTHESIS
BACKGROUND: Chronic kidney disease (CKD) is associated with endothelial dysfunction, but the link between cardiovascular risk and CKD is difficult to establish because other conditions such as diabetes, hypertension and transplant-related factors are present in these patients. Living donors are healthy individuals that represent a near-ideal experimental model of CKD since they undergo a time-defined reduction of GFR after nephrectomy in the absence of other confounding factors present in patients with mild to moderate CKD.
HYPOTHESIS: Reduction of GFR after donation is associated with increased while renal transplantation is associated with reduced endothelial dysfunction markers.
AIM: To prospectively evaluate biomarkers of endothelial dysfunction and surrogate variables of subclinical atherosclerosis in a cohort of living kidney donors before and one year after donation and in their recipients before and one year after transplantation.
PATIENTS AND METHODS: In two cohorts of 60 living kidney donors (1 month before and 1 year after donation) and in their 60 renal transplant recipients (1 month before and 1 year after transplantation) the following variables will be recorded: iohexol glomerular filtration rate (GFR), proteinuria, microalbuminuria, insulinemia, oral glucose tolerance test, total and LDL/HDL cholesterol, number of carotid plaques and intima-media thickness, carotid-femoral pulse wave velocity, ankle-brachial index, 24-hours ambulatory monitoring of blood pressure. The following biomarkers of endothelial dysfunction and subclinical inflammation will be determined: SVCAM-1, PTX3, ICAM-1, von Willebrand factor, E-selectin, platelet/endothelial cell adhesion molecule (PECAM1), interleukin 6 (IL-6), soluble receptor of tumor necrosis factor (sTNFR1 and sTNFR2), high sensitive C reactive protein (hs-CRP) and soluble TNF-like weak inducer of apoptosis (sTWEAK).
EXPECTED RESULTS. In healthy subjects decrease of renal function after living donation will be associated with increased endothelial dysfunction markers. On the contrary, after transplantation a decrease of endothelial dysfunction markers will be observed. Despite at one year both cohorts of patients will have a similar GFR, the investigators expect that amelioration of endothelial dysfunction in transplants will be higher than worsening of endothelial dysfunction in their donors. Thus, the study of these two cohorts will allow estimating the contribution of renal dysfunction per se and transplant-associated comorbidities to endothelial dysfunction in chronic kidney disease.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Endothelial dysfunction in Cohort 1 | – | Other: Endothelial dysfunctionAssessment of endothelial dysfunction in healthy subjects who will undergo a nephrectomy as part of the living donor program at each participating center. |
| Endothelial dysfunction in Cohort 2 | – | Other: Endothelial dysfunctionAssessment of endothelial dysfunction in renal transplant recipients from cohort 1 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Cohort 1 Healthy subjects who will undergo a nephrectomy as part of the living donor program at each participating center. Cohort 2 Renal transplant recipients from cohort 1
Key inclusion criteria (11 listed)
- No history of familiar nephropathies and/other diseases that may increase the risk for renal disease in the future.
- Donor age ≥ 18 years
- Isotopic GFR > 80 ml/min/1.73m2
- Microalbuminuria< 30 mg/g
- Normal urinary sediment
Key exclusion criteria (18 listed)
- History of cancer except non-melanoma cutaneous neoplasia
- History of vasculitis (e.g. lupus), sarcoidosis, gastrointestinal inflammatory diseases, autoimmune-disease
- History of major cardiovascular events
- History of deep vein thrombosis or pulmonary embolism.
- Active infection including hepatitis B, C and HIV infections.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endothelial dysfunctionOne month before surgery and one year after, the following procedures will be performed in donors and recipients: 1. Blood samples will be obtained for the measurement of endothelial dysfunction and low grade inflammation markers. 2. Atherosclerotic burden: carotid ultrasound to determine the number of plaques and intima-media thickness, carotid-femoral pulse wave velocity (m/s) will be performed by pulse tonometry. 3. Ambulatory blood pressure monitoring with overnight-automated ABPM monitor 4. Estimation of glomerular filtration rate by Iohexol method | Other | Endothelial dysfunction in Cohort 1, Endothelial dysfunction in Cohort 2 |
Primary outcome
Percentual change of sVCAM
Time frame: 1 year
Biomarker of endothelial dysfunction: Soluble VCAM (vascular cell adhesion molecule). Determination of serum levels by Luminex. Percentual change between baseline and 1 year levels.
14 secondary outcomes
Glomerular filtration rate
Time frame: 1 year
Microalbuminuria
Time frame: 1 year
Blood pressure (24 h ambulatory blood pressure measurement)
Time frame: 1 year
Number of carotid plaques and carotid intima-media thickness
Time frame: 1 year
Pulse wave velocity.
Time frame: 1 year
Percentual change of sICAM
Time frame: 1 year
Percentual change of PECAM
Time frame: 1 year
Percentual change of vWF
Time frame: 1 year
Percentual change of E-selectin
Time frame: 1 year
Percentual change of PTX3
Time frame: 1 year
Percentual change of hs-CRP
Time frame: 1 year
Percentual change of IL-6
Time frame: 1 year
Percentual change of sTNFR1 and sTNFR2
Time frame: 1 year
Percentual change of sTWEAK
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2017.
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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.
Francesc Moreso, MD, PhD principal investigator
Hospital Vall d'Hebron
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Disorder Related to Renal Transplantation and Chronic Kidney Disease, run by Hospital Universitari Vall d'Hebron Research Institute at 4 sites in Spain.
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 11 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 28 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Spain. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Francesc Moreso, MD, PhD (+34932746079, fjmoreso@vhebron.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentual change of sVCAM (time frame: 1 year). 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 28 Mar 2017.