Impact of Low Protein Diet Supplemented With Ketoanalogues Supplementation on Uremic Toxins Production

Impact of Low Protein Diet Supplemented With Ketoanalogues on Uremic Toxins Production and Glucose Metabolism in Chronic Kidney Disease

Chronic kidney disease (CKD) is associated with accumulation of uremic toxins like p-cresyl sulfate and indoxyl sulfate that are associated of cardiovascular complication and perturbation of glucose metabolism. These toxins are produced by fermentation of protein by intestinal microbiota but the role of low protein diet and ketoanalogue supplementation on uremic toxins production and microbiota composition are unknown. Low protein diet supplemented with ketoanalogues is recommended inCKD patients to prevent progression of renal disease. The aim of this study is to determine the impact of uremic toxins concentration, microbiota composition and gut hormone involved in carbohydrate metabolism ( GLP-1, FGF19, bile acids) with low protein diet supplemented with ketoanalogues.

Inclusion Criteria:

• CKD stage 4-5 with estimated glomerular filtration rate < 30 ml/min/1,73m2
• No dialysis
• No history of kidney transplantation
• Non-diabetic (fasting glucose <1.26 g / L, or no insulin or oral antidiabetic therapy)
• BMI between 18 and 30 kg / m2
• Patient followed in the nephrology department of Professor FOUQUE at the Lyon Sud hospital
• For women of childbearing age, at least one method of contraception recognized as effective
• Patient who gave consent to open participation and signed the consent to participate in the study

Exclusion Criteria:

• Patient with progressive inflammatory, infectious, cardiovascular or neoplastic disease
• Patient refusing a dietary follow-up
• Patient having a planned transplant or dialysis project in the next 6 months.
• Patient having a colectomy, resection of the small intestine or cholecystectomy
• Patient who has received antibiotics, prebiotics, probiotics in the last 3 months.
• Patient treated with more than 2 g of calcium per day
• Patient using laxatives (more than 2 per day)
• Patient having:
• Uncontrolled metabolic acidosis (bicarbonatemia <18 mM)
• Hyperparathyroidism (PTH greater than 5 times the upper limit of normal)
• Hypercalcemia (Calcium> 2.55 mmol / L) or hypophosphoremia <0.70 mmol / L
• Anemia (hemoglobinemia <80g / L)
• Undernutrition criteria: albumin <38 g / L or prealbumin <0.3 g / L
• Known hypersensitivity to any of the substances or excipients of Ketosteril
• Subject in exclusion period of a previous study
• Patient not affiliated to social security
• Patient under guardianship or in the interests of justice
• Patient who is pregnant, breastfeeding or likely to become pregnant during the study