Major Activation Of NCC in Graft Urinary Exosomes

Study Overview
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Brief Summary
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Hypertension is common disorder after renal transplantation and is associated with mortality. Calcineurin Inhibitor (CNI), by activating NCC cotransporter, may be a major determinant of hypertension, included in a Gordon like syndrome. However, prevalence of NCC activation by CNI is unknown. Our objective is to determine the prevalence of NCC activation three months after transplantation in patient treated by CNI.

Detailed Description
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Hypertension is common disorder after renal transplantation and is associated with mortality. Calcineurin Inhibitor (CNI), by activating NCC cotransporter, may be a major determinant of hypertension, included in a Gordon like syndrome. Gordon syndrome is a rare genetic disorder where NCC cotransporter is overactivated and cause hypertension, metabolic acidosis and tendency to hyperkaliemia. Few studies evaluated NCC expression by exosomes techniques in human kidney transplant, and mostly compared NCC expression in specific subpopulation (for example with or without hypertension). Thus, prevalence of NCC activation by CNI is unknown. To determine it, we will include prospective patients in Bordeaux and la Réunion who undergo urine and blood tests three months after transplantation, and a control group with no transplantation and no use of CNI. First, we will compare kidney recipients and control and use immunoblot to quantify NCC expression in urinary exosomes to identify the population of transplanted with a high activation. Then, we will analyze the relationship between NCC activation and clinicobiological features of Gordon's syndrome.

Official Title
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Evaluation of the Prevalence of an Hyperactivation of NCC Cotransporter Three Months After Kidney Transplantation in Recipients Treated by Calcineurin Inhibitors

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Other: exosomes analysis


Participation Criteria
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Eligibility Criteria
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For kidney transplant group : inclusion criteria: Age≥18years Recipients three months after kidney transplantation using calcineurin inhibitors Glomerular Filtration Rate>15ml.mn.m2 CKD-EPI Renal ultrasound underwent before inclusion No opposition at participating at the research exclusion criteria: Use of diuretic thiazides or aldosterone receptor antagonists in the month preceding inclusion Graft artery stenosis with indication of interventional radiology or surgery For control group : Inclusion criteria No previous transplantation Age≥18years No hypertension No metabolic disorders (dysnatremia, dyskaliemia, acidosis or alkalosis) No opposition at participating at the research Exclusion criteria: Use of diuretic thiazides or aldosterone receptor antagonists in the month preceding inclusion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control group<br>Control group is a population of subjects admitted to day hospitalization for renal function tests or in conventional hospitalization, but without kidney transplant. Exosome analysis will be perform in urine sample. | Other: exosomes analysis<br>* Perform exosomes analysis in urine sample obtain from usual urine testing in both kidney transplant and control group.<br>|
| Kidney transplants group<br>Kidney transplants group is a kidney transplant subjects population 3 months ago. Exosome analysis will be perform in urine sample collected at 3 months. | Other: exosomes analysis<br>* Perform exosomes analysis in urine sample obtain from usual urine testing in both kidney transplant and control group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NCC cotransporter expression | Dosage of NCC cotransporter expression in urinary exosomes samples in both groups. | Inclusion day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phosphorylated NCC cotransporter expression | Dosage of phosphorylated NCC cotransporter expression in urinary exosomes samples in both groups. | Inclusion day | 
| pendrine expression in kidney transplant group | Dosage of pendrine expression in urinary exosomes samples in kidney transplant group. | Inclusion day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcineurin inhibitors, hypertension, kidney transplant, acidosis, Gordon syndrome