Major Activation Of NCC in Graft Urinary Exosomes (MANGUE)

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Other: exosomes analysis

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 67

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33000
    • Hopital Pellegrin - Service Néphrologie, transplantation, dialyse et aphérèse
• Réunion
  • Saint-Denis, Réunion, 97400
    • Hopital Felix Guyon - Service d'Explorations Fonctionnelles Rénales

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Kidney transplant group is a population of transplant subjects treated with anticalcineurin since 3 months.

Control group is a population of subjects admitted to day hospitalization for renal function tests or in conventional hospitalization, but without kidney transplant.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control group; 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; Perform exosomes analysis in urine sample obtain from usual urine testing in both kidney transplant and control group.
Kidney transplants group; 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; Perform exosomes analysis in urine sample obtain from usual urine testing in both kidney transplant and control group.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 21, 2018
• Primary Completion (ACTUAL): August 31, 2018
• Study Completion (ACTUAL): August 31, 2018

Study Registration Dates

• First Submitted: April 11, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (ACTUAL): April 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 12, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: hypertension; kidney transplant; acidosis; Calcineurin inhibitors; Gordon syndrome
• Other Study ID Numbers: CHUBX 2018/08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No