Contribution of Renal Function to Endothelial Dysfunction in Living Kidney Donors and Transplant Recipients
- Conditions
- Endothelial DysfunctionDisorder Related to Renal TransplantationChronic Kidney Disease
- Interventions
- Other: Endothelial dysfunction
- Registration Number
- NCT02515643
- Brief 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 transplant recipients.
Secondary objectives
To evaluate in both cohorts of patients before and after nephrectomy/transplantation the evolution of the following parameters:
1. Renal function (iohexolGFR, proteinuria/microalbuminuria).
2. Blood pressure (24 h ambulatory blood pressure measurement)
3. 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Endothelial dysfunction in Cohort 1 Endothelial dysfunction Assessment 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 Endothelial dysfunction Assessment of endothelial dysfunction in renal transplant recipients from cohort 1
- Primary Outcome Measures
Name Time Method Percentual change of sVCAM 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.
- Secondary Outcome Measures
Name Time Method Microalbuminuria 1 year Microalbuminuria (mg/g creatinine) will be determined before donation and at 1 year in donors and at 1 year in transplant recipients.
Percentual change of PTX3 1 year Biomarker of endothelial dysfunction: PTX3 (pentraxin). Determination of serum levels by ELISA. Percentual change between baseline baseline and 1 year levels.
Glomerular filtration rate 1 year 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.
Percentual change of E-selectin 1 year Biomarker of endothelial dysfunction: Soluble E-selectin. Determination of serum levels by Luminex.Percentual change between baseline baseline and 1 year levels.
Percentual change of sTWEAK 1 year 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.
Pulse wave velocity. 1 year Carotid-femoral pulse wave velocity (m/s) will be measured by pulse tonometry (Sphingmocor Atcor, EM3, Australia).
Number of carotid plaques and carotid intima-media thickness 1 year 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),
Percentual change of sICAM 1 year Biomarker of endothelial dysfunction: Soluble ICAM (intercellular adhesion molecule). Determination of serum levels by Luminex. Percentual change between baseline baseline and 1 year levels.
Percentual change of sTNFR1 and sTNFR2 1 year 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.
Blood pressure (24 h ambulatory blood pressure measurement) 1 year Ambulatory blood pressure monitoring (mm Hg) with overnight-automated ABPM monitor (Spacelab 90207; Spacelabs Healthcare,USA) with appropriate cuff sizes for each patient.
Percentual change of PECAM 1 year 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.
Percentual change of vWF 1 year Biomarker of endothelial dysfunction: vWF (von Willebrand factor). Determination of serum levels by Luminex. Percentual change between baseline baseline and 1 year levels.
Percentual change of hs-CRP 1 year 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.
Percentual change of IL-6 1 year 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.
Trial Locations
- Locations (4)
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitario Canarias
🇪🇸Santa Cruz de Tenerife, Islas Canarias, Spain
Vall d'Hebron Research Institute
🇪🇸Barcelona, Spain
Hospital Regional Universitario Carlos Haya
🇪🇸Malaga, Spain