FGF19 and Chronic Kidney Disease

Hospices Civils de Lyon170 enrolled

Overview

Sarcopenia in chronic kidney disease (CKD) affects 50% of dialysis patients and 20% of patients with non-dialyzed CKD and reduce quality of life and survival. The pathophysiology of uremic sarcopenia is multifactorial (accumulation of toxins, metabolic disturbances, etc.) and poorly characterized. These pejorative factors are associated with malnutrition and a sedentary lifestyle. Currently, there are no strategies to combat sarcopenia with the exception of physical activity, which is only possible for a limited number of patients due to their comorbidities. Developing new pharmacological strategies to combat sarcopenia is necessary. FGF19 is a growth factor produced in the ileum involved in metabolic homeostasis. In the laboratory, a new function of FGF19 has been discovered. FGF19 acts as a hormonal factor stimulating muscle mass and strength. Preliminary studies had shown a decrease in the concentration and secretion of FGF19 in response to a meal in haemodialysis patients. However, the link between FGF19, muscle mass and CKD has never been demonstrated. The aim of this study is to assess the relationship between the concentration and secretion of FGF19 and muscle function in a large population of patients with CKD of different stages. Given the hormonal communication between the bone and the muscle, the investigators will also recover the bone histological parameters from a bone biopsy if dialysis patients are to benefit from this as part of their follow-up. The investigators hypothesize that a decrease in FGF19 concentration and secretion in CKD is associated with a decrease in muscle mass and strength.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

170

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: -For the patient population: * estimated GFR \<60 ml / min / 1.73m2 according to the CKD-EPI formula OR patients dialyzed for more than 3 months * No history of kidney transplant * BMI between 18 and 30 kg / m² * For women of childbearing age, at least one method of contraception recognized as effective * Willing and able to give informed consent For control group: * Potential living kidney donor * Willing and able to give informed consent For all of the study participants: o Non diabetic (fasting blood glucose \<1.26 g / L, or absence of insulin or oral antidiabetic treatment) Exclusion Criteria: * For the patient population: * Subjects with a history of colectomy, gut resection or cholecystectomy * Having received antibiotics, prebiotics, probiotics in the last 3 months. * Taking a high dose laxative treatment (\> 2 doses per day) in the last 3 months * Hemoglobin \<7 g / dl or \<9 g / L in case of previous cardiovascular disease * For control group: * DFGe ≤ 80 ml / min / 1.73m2 according to CKD-EPI * High blood pressure (PA≥140 / 90 mmHg) or taking antihypertensive treatment * Presence of proteinuria (\> 0.15 g / 24h) or micro-albuminuria (\> 3 mg / mg creatinuria) or hematuria (\> 20 GR / mm3) * For all of the study participants: * Hemoglobin \<7 g / dl or \<9 g / L in case of previous cardiovascular disease * Active inflammatory, infectious, cardiovascular or neoplastic disease * Period of exclusion from a previous study or already participating in a clinical research protocol having an impact on the study judgment criteria * Exposure to ionizing radiation (medical radiological examinations or occupational exposure with exposure greater than 20 mSv) in the 6 months preceding inclusion * No affiliation to social security * Patient under guardianship or safeguarding justice * Pregnant patient (a pregnancy test will be carried out for women of reproductive age o For the patients and control group will accept muscles biopsies * Presence of a precarious venous capital that does not allow the placement of a venous catheter - Thrombocytopenia * History of arrhythmias or cardiac conduction disorders * Taking anticoagulant and / or antiplatelet agent * Pulse \<50 bpm * Allergy to local anesthetics and / or plaster

Outcomes

Primary Outcomes

Correlation between the fasting plasma concentration of FGF19 and the muscle mass

Study the correlation between the fasting plasma concentration of FGF19 and the muscle mass in % of body weight, measured by DEXA scanner (Dual-X-Ray-Absorptiometry) in non-dialyzed MRC patients with a measured glomerular filtration rate (mDFG) \<60 ml / min /1.73m², hemodialysis patients and healthy voluntary being assessed for a kidney donation or a nephrological check-up with no renal pathology..