Ketoanalogue-Supplemented Vegetarian Very Low-Protein Diet and CKD Progression

Abstract

Dietary protein restriction may improve determinants of CKD progression. However, the extent of improvement and effect of ketoanalogue supplementation are unclear. We conducted a prospective, randomized, controlled trial of safety and efficacy of ketoanalogue-supplemented vegetarian very low-protein diet (KD) compared with conventional low-protein diet (LPD). Primary end point was RRT initiation or >50% reduction in initial eGFR. Nondiabetic adults with stable eGFR<30 ml/min per 1.73 m(2), proteinuria <1 g/g urinary creatinine, good nutritional status, and good diet compliance entered a run-in phase on LPD. After 3 months, compliant patients were randomized to KD (0.3 g/kg vegetable proteins and 1 cps/5 kg ketoanalogues per day) or continue LPD (0.6 g/kg per day) for 15 months. Only 14% of screened patients patients were randomized, with no differences between groups. Adjusted numbers needed to treat (NNTs; 95% confidence interval) to avoid composite primary end point in intention to treat and per-protocol analyses in one patient were 4.4 (4.2 to 5.1) and 4.0 (3.9 to 4.4), respectively, for patients with eGFR<30 ml/min per 1.73 m(2) Adjusted NNT (95% confidence interval) to avoid dialysis was 22.4 (21.5 to 25.1) for patients with eGFR<30 ml/min per 1.73 m(2) but decreased to 2.7 (2.6 to 3.1) for patients with eGFR<20 ml/min per 1.73 m(2) in intention to treat analysis. Correction of metabolic abnormalities occurred only with KD. Compliance to diet was good, with no changes in nutritional parameters and no adverse reactions. Thus, this KD seems nutritionally safe and could defer dialysis initiation in some patients with CKD.

Keywords: nutrition; phosphate binders; progression of chronic renal failure; renal function decline.

Figure 1.

Study phases and patients’ flowchart. The enrolled patients entered a run-in phase; the compliant ones were randomized for the intervention.

Figure 2.

Adjusted event–free survival rates of patients assigned to the KD or the LPD. The probability to reach the end-point was even lower in KD group when adjusted for the other significant predictors of outcome in a Cox proportional hazard model.

Figure 3.

Median eGFR throughout the study. There were no significant differences in eGFR between LPD and KD groups at any moment.

Figure 4.

Median changes in eGFR (95% CI) between study moments (Δ implies statistically significant difference between the two groups). EOS, end of study. (A) In the first 3 months after randomization, eGFR significantly increased in KD arm and decreased in LPD. (B) The decrease in eGFR was lower in KD when considering the interval between 3 months after randomization and the end of study.

Figure 5.

Serum bicarbonate (milliequivalents per liter) during the study. Serum bicarbonate was lower at baseline in KD, but increased significantly in this arm.

Figure 6.

(A) Serum calcium (milligrams per deciliter) and (B) serum phosphates (milligrams per deciliter) during the study. Serum calcium increased and serum phosphates decreased only in KD arm; opposite variations were seen in the LPD group.

Figure 7.

Protein intake (median and 95% CI) during the study. The achieved protein intake was very close to prescription and stable throughout the study.