Contribution of Renal Function to Endothelial Dysfunction in Living Kidney Donors and Transplant Recipients

Overview

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.

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.