Supplemented Very Low Protein Diet and the Progression of Chronic Kidney Disease (KETOPROG)

Effect of Very Low Protein Diet Supplemented With Ketoanalogues of the Essential Amino Acids on the Progression of Chronic Kidney Disease

This is a prospective single center randomized controlled trial with a total duration of 18 months aiming to evaluate the effectiveness and the safety of a very low protein diet supplemented with ketoanalogues of essential aminoacids in reducing the progression of chronic kidney disease (CKD) in patients with advanced CKD.

All eligible patients who will give informed consent will be screened. Those meeting the selection criteria will be enrolled and will enter a 3-month run-in phase during which a conventional LPD will be prescribed in all patients. At the end of this phase, the subjects still fulfilling all the selection criteria will be randomized in a 1:1 ratio to receive the KD or to continue the conventional LPD for a total duration of 15 months. Nineteen blood and urine samplings are scheduled for each patient, to be drawn monthly. The laboratory reports include the nitrogen compounds, calcium-phosphorus metabolism parameters, acid-base balance, biochemical nutritional markers, serum C-reactive protein, hemoglobin, blood cell count, and biochemical safety parameters (sodium, potassium, liver enzymes, and bilirubin). The anthropometric measurements and subjective global assessment will be evaluated at enrolment, at randomization, and every 3 months thereafter. The compliance with the prescribed diet (protein and energy intake) will be assessed monthly during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and every 3 months thereafter. The blood pressure levels, drugs required for the therapy of hypertension, acidosis and mineral metabolism disorders, and occurrence of adverse events will be recorded monthly.

Patients in the intervention arm (KD group) will receive a vegetarian very low protein diet (0.3 g proteins/kg ideal body weight per day) supplemented with ketoanalogues of essential amino acids (Ketosteril®, Fresenius Kabi, Bad Homburg, Germany), 1 capsule for every 5 kg of ideal dry body weight per day.

The patients in the control arm (LPD group) will continue their conventional low protein diet, with 0.6 g/kg per day (including high biological value proteins). The total recommended energy intake is of 30 kcal/kg of ideal dry body weight per day in both arms.

Need for renal replacement therapy or an at least 50% reduction in the estimated glomerular filtration rate compared to randomization

Inclusion Criteria: adult non-diabetic patients stage 4-5 CKD not on dialysis (estimated glomerular filtration by Modification of Diet in Renal Disease formula < 30 mL/min per year stable renal function at least 12 weeks before enrollment well-controlled arterial blood pressure proteinuria less than 1 g/g urinary creatinine good nutritional status declared and anticipated good compliance with the prescribed diet Exclusion Criteria: poorly controlled arterial blood pressure (≥145/85 mm Hg) relevant comorbid conditions (diabetes mellitus, heart failure, active hepatic disease, digestive diseases with malabsorption, inflammation/anti-inflammatory therapy) uremic complications (pericarditis, polyneuropathy) feeding inability (anorexia, nausea)

Mircescu G, Garneata L, Stancu SH, Capusa C. Effects of a supplemented hypoproteic diet in chronic kidney disease. J Ren Nutr. 2007 May;17(3):179-88. doi: 10.1053/j.jrn.2006.12.012.

Hahn D, Hodson EM, Fouque D. Low protein diets for non-diabetic adults with chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 29;10(10):CD001892. doi: 10.1002/14651858.CD001892.pub5.