Low-Protein Diet Supplemented with Ketoanalogues and Progression of Chronic Kidney Disease in Diabetic Patients: A Multicenter Randomized Controlled Trial

Background/Objectives: Low-protein diets (LPD) and very-low-protein diets supplemented with Ketoanalogues (sVLPD) delay initiation of dialysis in non-diabetic patients with chronic kidney disease (CKD). sVLPD is not recommended in patients with type 2 diabetes mellitus (T2DM), and information about LPD supplemented with Ketoanalogues (LPD + KA) is scarce or inconclusive. The objective of this study is to provide further evidence on the benefits and safety of LPD supplemented with KA (LPD + KA) compared with LPD alone in reducing CKD progression in patients with T2DM. Methods: T2DM patients in stages 3b-4 of CKD (n = 149) were included in a multicenter, randomized, controlled trial and received LPD + KA or LPD, 1 year follow-up. Evaluations were carried out bimonthly. In both groups, protein intake was 0.6 g/kg/day, and the LPD + KA group received KA at the recommended dose. The primary outcome was a decline in eGFR, calculated with Creatinine and with Cystatin C. Secondary outcomes were dialysis requirement, deterioration in nutritional status, hospitalization, morbidity, and mortality. Results: During follow-up, protein nitrogen appearance was 0.556 ± 0.119 and 0.576 ± 0.134 g/kg/day in LPD + KA and LPD, respectively (p = 0.002). The decrease in eGFRCysC from the baseline was −4.29 ± 0.96 mL/min in LPD + KA and −8.54 ± 2.19 mL/min in LPD (using linear mixed-effects model, p = 0.012). eGFRCr did not show differences. There were no differences in nutrition status, metabolic control, adverse events, hospitalizations, or hospital days. Conclusions: Ketoanalogues slow the decline in eGFRCyC but not eGFRCr in T2DM patients, even without differences in protein intake. LPD + KA may be considered useful and safe; however, due to limitations in sample size and follow-up, as well as observed changes in Cr metabolism, the results warrant confirmation with a more robust design and a longer follow-up period.