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Recommendations Summary

CKD: Macronutrients: Protein Type (2020)

Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.

  • Recommendation(s)

    CKD: Macronutrients: Protein Type

    In adults with CKD 1-5D, there is insufficient evidence to recommend a particular protein type (plant vs animal) in terms of the effects on nutritional status, calcium or phosphorus levels, or the blood lipid profile (1B).

    Rating: Strong

    CKD: Macronutrients: Protein Type, Post-Transplant

    In adults with CKD posttransplantation, there is insufficient evidence to recommend a particular protein type (plant vs animal) in terms of the effects on nutritional status, calcium or phosphorus levels, or the blood lipid profile (OPINION).

    Rating: Consensus

    • Risks/Harms of Implementing This Recommendation

      There are no obvious risks or harms associated with this recommendation. Compliance to diets should be monitored frequently during the first year of dietary intervention by dietary interviews (3 is optimal) and urine collection for urea output measures. Then yearly follow-up may be recommended until start of maintenance dialysis

    • Conditions of Application

      So far, vegetarian protein diet (VPD) have not specifically been studied to test metabolic hypotheses in CKD. Particularly, the fact that phosphorus may be less absorbed during a VPD diet may benefit calcium and phosphate metabolism. This becomes more important since currently processed food contains much added inorganic phosphorus as compared with VPD. The fat content of VPD possesses a healthier profile and may benefit patients in long-term studies. Finally, toxic middle molecules such as P-cresyl sulfate, indoxyl-sulfate and trimethylamine oxide (TMAO), almost exclusively produced from animal source protein, have been reduced by VPD and this hypothesis should be tested in long-term clinical trials in CKD patients. As demonstrated in other subtopics of this guidelines, VPD has shown reduction in acid load, increase in dietary fiber intake, reduction of phosphorus, and body weight. There is increasing interest in the role of VPD in CKD due to the benefits of this dietary pattern on cardiovascular disease risk factors in the general population. However, current evidence from RCTs specifically comparing benefits of VPD vs APD in CKD patients is limited.

      Implementation Considerations

      • Work with you CKD patients to help them meet their individualized dietary protein intake needs.
      • Based on CKD patients preference for animal or plant based protein ensure that they meet their dietary protein needs and that their diets provide adequate essential amino acids.

    • Potential Costs Associated with Application

      Although costs of MNT sessions and reimbursements vary, MNT sessions are essential for improving outcomes.

    • Recommendation Narrative

      Vegetable protein diets (VPD) may have beneficial effects on health.  A recent population-based study suggested soy or soy isoflavones intake significantly reduced the risk of postmenopausal breast cancer (Wada et al 2013). Oxidative stress significantly decreased in postmenopausal women when treated with VPD (soy isoflavones) and in vitro experiments have shown that VPD protects against inflammation in vascular endothelial cells (Jing et al 2016).These findings lead to the development of preventive strategies for human health and disease. For example, the US Food and Drug Administration suggested that the intake of 25 g soy protein daily may prevent the risk of coronary heart disease because of reduced serum lipids and lipoproteins.

      In patients with chronic kidney disease (CKD), VPD may have positive biological actions and possibly clinical benefits through a variety of mechanisms. In vitro studies showed that VPD reduce the expression of renin-angiotensin (Frigolet et al 2012). Studies in rodents demonstrated that VPD retard the development and progression of CKD, vs animal protein diets (APD) (Iwasaki et al 1988), presumably through favorable effects on glomerular filtration rate (GFR). In addition, in pre-dialysis CKD patients, Moe et al. reported that a vegetarian diet, although it may contain eggs and dairy products, was associated with a significant reduction in serum phosphate and FGF-23 levels and a decrease in 24-hour urinary phosphorus excretion, despite equivalent energy, protein and phosphorus intake, compared with a meat diet (Moe et al 2011). As a result, it was thought that VPD may be used in helping to reduce phosphorus load and CKD progression in this group of patients.

      Detailed Justification
      Three randomized controlled trials (HD & PD) and two randomized crossover (Stage 3-4 CKD) trials compared the impact of vegetable-based protein (VPD) vs animal -ased (APD) protein intake on biomarkers and health outcomes in patients with CKD.

      Protein type did not affect nutritional status as measured by serum albumin. In Soroka et al. serum albumin significantly increased after both VPD and APD, compared to the pre-study diet, but there was no significant difference on serum albumin between VPD and APD (Soroka et al 1998). Fanti et al. found no significant difference between VPD and APD on albumin levels.Tabibi et al., found a significant (p<0.05) increase in serum albumin levels within both groups, but no significant difference found between groups.Finally, Chen et al. found no significant differences in albumin between groups. However, the power to discriminate might have been insufficient due to the small number of patients enrolled.  In pooled analysis of four studies, there was no effect of protein type on albumin levels.

      Protein Catabolic Rate (PCR)
      VPD may be associated with a decrease in PCR after 6 months, but evidence was limited. In Saroka et al., PCR was significantly (p<0.05) lower after 6 month of VPD compared to the pre-study diet, but there were no changes in the APD diet. In a secondary analysis, there was a mean difference (95% CI) of -0.10 (-0.17, -0.03) g/kg/d in PCR values in the VPD vs the APD. This might have been the consequence of a slightly reduced absorption of protein from vegetal source (estimated to be 90% of animal protein).

      Pre-Albumin Levels
      VPD did not affect serum pre-albumin levels compared to a control group, but evidence was limited. Fanti et al. found no significant difference between VPD and APD on serum albumin or pre-albumin levels after receiving soy protein for 8 weeks, compared to the control group.

      Inflammatory Markers (CRP, IL-6, TNF-α)
      Protein type did not affect inflammatory markers. Fanti et al. compared the impact of a soy protein vs a milk protein supplement on inflammation.  No significant differences were found within or between groups for CRP, IL-6 or TNF-α levels. 

      Calcium and Phosphorus Levels
      There was no effect of protein type on plasma/serum or urinary calcium levels. VPD for 7 days to 6 months did not affect plasma/serum phosphate levels, but did decrease 24-hour urinary phosphate levels by a mean difference of -126.6 (-200.4, -52.7) mg. Soroka et al. found no significant difference between VPD, APD, or pre-study diet on urinary sodium, potassium or calcium; or serum calcium or phosphate. Urinary phosphate was significantly lower after the VPD vs the APD and pre-study diet.  In a small randomized crossover trial, Moe et al. demonstrated that plasma phosphate levels were significantly higher in the APD vs the VPD group at day 7 (p=0.02), but there was no difference in urinary phosphorus excretion. There were no differences in plasma calcium or urinary calcium excretion levels between groups.  In pooled analysis of these 2 studies, there was no effect of VPD, compared to APD, on serum/plasma phosphate. However, VPD did decrease 24-hour urinary phosphate levels by a mean difference (95% CI) of -126.6 (-200.4, -52.7) mg.

      Total, LDL and HDL Cholesterol, Triglyceride Levels
      Protein type did not affect lipid profile in MHD, PD or Stage 4 CKD patients. Three studies examined the effect of VPD vs APD on blood lipid panel. Chen et al. compared the impact of a soy protein vs a milk protein supplement on plasma lipids during 12 weeks in MHD patients with and without hyperlipidemia.  In patients without hyperlipidemia, no significant differences were found in total cholesterol, LDL-C, HDL-C and triglycerides levels within or between groups. In hyperlipidemic patients however, soy protein lead to a significant decrease in total cholesterol, LDL cholesterol and triglyceride levels, compared to milk protein, whereas HDL significantly increased. Tabibi et al. compared the impact of a soy protein supplement vs control in PD patients and found no significant impact on total cholesterol, LDL-C, HDL-C and triglycerides levels in the intervention group. Soroka et al found no significant differences after VPD, APD or pre-study diet on total cholesterol, LDL-C and triglycerides TG, in stage 4 CKD patients. HDL-C level was significantly lower after VPD compared to the pre-study diet. In pooled analysis of 3 studies, there was no mean difference in total, LDL or HDL-C levels or triglyceride levels between groups.

    • Recommendation Strength Rationale

      The evidence supporting the recommendation on protein type is based on Grade II /Grade B evidence for CKD 1-5D. The evidence supporting for PD is based on Consensus/expert opinion.

    • Minority Opinions

      Consensus reached.