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.