Restriction of Proteins in the Diet and Supplementation With Ketoanalogues to Prevent Disease Progression in Patients With Stage 4 Chronic Kidney Disease

Design. A multicenter, controlled, randomized, open label clinical trial was performed in patients with T2DM in CKD stage 3b-4 (GFR <44 to >15 mL/min/1.73 m2) treated in hospitals of the Mexican Social Security Institute. The follow-up period was at least 1 year from the inclusion of the last patient. The study was conducted in accordance with the provisions of the Declarations of Helsinki and Tokyo with the amendments in Venice (1983). The protocol was approved by the National Research and Ethics Committee and by the Research Committees of all participating hospitals and was registered in National Clinical Trials (NCT03818568).

Patients. Inclusion criteria: Adult patients with T2DM (>18 years) of either sex, with stage 3b-4 of CKD. All patients gave their signed informed consent at the time of recruitment. Exclusion criteria: Previous treatment with KA, kidney transplantation, cancer, HIV-AIDS, or seropositive for hepatitis B or C, patients receiving immunosuppressors, with hypercalcemia, intolerance to KA or disorders of amino acid metabolism. Patients who lost social security during the study, changed address or treating physician were also excluded.

Sample size. Sample size calculation was made on the basis of two independent groups with unequal variances, α=0.05, β=0.20, and assuming a difference of 4.0 mL/min/yr between groups in reduction of eGFR, lower in LPD+KA. Calculation was made with sample size software. A minimum of 51 per group was obtained.

Intervention. Diet design. Energy: 35 kcals/kg of ideal body weight in patients with normal BMI; 30 kcals/kg of ideal body weight in overweight patients (BMI>25 kg/m2) and 40 kcals/kg of ideal weight in underweight patients (BMI<25 kg/m2). Lipids accounted for 35% of the total energy intake (2/3 from polyunsaturated fatty acids). Carbohydrate intake was set at 55-60% of the total energy intake, with >70% of complex carbohydrates. The fiber content was 20-25 g per day. The dietary recommendation for sodium chloride was ~5 g daily and potassium 50-60 mEq/day. Phosphate intake was set at 800-1000 mg per day.

Both groups were prescribed with PrI of 0.6 g/kg/day, preferably plant-based. Patients in LPD+KA group received KA (Ketosteril® (Fresenius Kabi, Deutschland GMBH, BadHomburg, Germany) according to the manufacturer's recommendations (1 tablet/5 kg of body weight divided into 3 doses). All other treatments were provided according to institutional guidelines and prescribed by and according to the criteria of the treating physicians.