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

LPD supplemented with ketoanalogues resulted in a significantly smaller decline in eGFR as measured by Cystatin C compared to LPD alone.

• The decrease in eGFRCysC from baseline was -4.29 ± 0.96 mL/min in the LPD + KA group versus -8.54 ± 2.19 mL/min in the LPD group.
• The difference was statistically significant using a linear mixed-effects model (p = 0.012).
• Follow-up was 1 year with bimonthly evaluations.
• Patients were in CKD stages 3b-4 with type 2 diabetes mellitus (n = 149).

eGFR measured by serum creatinine (eGFRCr) did not differ significantly between the LPD + KA and LPD groups.

• Despite the significant difference seen with Cystatin C-based eGFR, creatinine-based eGFR showed no statistically significant differences between groups.
• The authors attributed this discrepancy to possible changes in creatinine metabolism associated with ketoanalogue use.
• This divergence between the two eGFR measures was noted as a key limitation requiring further investigation.

Actual protein intake as measured by protein nitrogen appearance was low and similar in both groups, with a small but statistically significant difference.

• Protein nitrogen appearance was 0.556 ± 0.119 g/kg/day in the LPD + KA group and 0.576 ± 0.134 g/kg/day in the LPD group (p = 0.002).
• Both groups were prescribed a protein intake of 0.6 g/kg/day.
• The authors noted the benefit of ketoanalogues occurred 'even without differences in protein intake,' suggesting a mechanism beyond protein restriction alone.

There were no significant differences between LPD + KA and LPD groups in nutritional status, metabolic control, adverse events, hospitalizations, or hospital days.

• Secondary outcomes evaluated included dialysis requirement, deterioration in nutritional status, hospitalization, morbidity, and mortality.
• No significant differences were found in any of these secondary outcomes.
• The authors concluded that LPD + KA 'may be considered useful and safe' in T2DM patients with CKD stages 3b-4.

Very-low-protein diets supplemented with ketoanalogues (sVLPD) are not currently recommended for patients with type 2 diabetes mellitus, and evidence for LPD + KA in this population was previously scarce or inconclusive.

• The trial was designed to address this evidence gap specifically in T2DM patients in CKD stages 3b-4.
• Prior evidence supported sVLPD for delaying dialysis initiation in non-diabetic CKD patients.
• This multicenter randomized controlled trial (n = 149) was conducted by the Mexican Nephrology Collaborative Study Group.

The authors identified key limitations including sample size, follow-up duration, and changes in creatinine metabolism that warrant confirmation with a more robust study design.

• The authors stated '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.'
• The divergence between eGFRCysC and eGFRCr outcomes was highlighted as a methodological concern.
• The study followed patients for 1 year, which the authors considered potentially insufficient.