INTRODUCTION: The supplementation with Ketoanalogues in patients on very low-protein diets has shown a favorable effect on the evolution of renal function. The aim of the present study was to evaluate the progression of renal function in advanced chronic kidney disease patients on a low-protein diet (<0.8 g/kg/d) with or without additional Ketoanalogues. METHODS: The primary criterion is the evolution of the renal function at 6, 12, and 24 months for the two groups. The secondary criteria comprise the evolution of the body weight, mean blood pressure, 24-h proteinuria, salt and protein consumption, energy consumption, hemoglobin levels, serum albumin, prealbumin, C-reactive protein, liver function tests, serum electrolyte and phosphate levels, parathormone as well as calcium levels at the same time periods. RESULTS: There was a significant nephroprotective effect of the Ketoanalogues after 12 and 24 months with no differences in the protein consumption between the two groups. Mean blood pressure, hemoglobin levels, 24-hour proteinuria, serum electrolyte, liver function tests, salt and protein consumption, and serum albumin and prealbumin did not present any significant differences. Serum bicarbonate and calcium levels were higher while serum phosphate and parathormone levels were lower in the Ketoanalogue group at all follow-up time points. During the 24-month follow-up period, 4 patients from the Ketoanalogue group and 8 patients from the control group quit the study. CONCLUSION: A low-protein diet supplemented with Ketoanalogues exerts significant nephroprotective effects and better bone mineral metabolism parameters compared to a low-protein diet only.