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Recommendations Summary

CKD: Macronutrients: Dialysate (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: Dialysate Protein-Energy Supplementation

    In adults with CKD 5D on PD with protein-energy wasting, we suggest not substituting conventional dextrose dialysate with amino acid dialysate as a general strategy to improve nutritional status, although it is reasonable to consider a trial of amino acid dialysate to improve and maintain nutritional status if nutritional requirements cannot be met with existing oral and enteral intake (OPINION). 

    Rating: Consensus
    Conditional

    • Risks/Harms of Implementing This Recommendation

      Mild acidosis may occur in some patients,  although it is readily treatable. In diabetic patients on peritoneal dialysis (PD) with uncontrolled hyperglycemia, substituting amino acid for glucose in PD solutions may serve as an immediate strategy for glycemic control.

    • Conditions of Application

      The recommendation statement is based on two randomized-controlled and one non-randomized crossover trials. The included studies only assessed intermediate nutrition-related outcome measures, including dietary intake (total energy and protein intakes, and oral energy intake); laboratory markers of nutritional status (albumin, pre-albumin, transferrin, and total protein levels); and anthropometry (MAMC, triceps skinfold and fat mass). The effects of substituting amino acid dialysate for conventional dextrose dialysate on patient survival, hospitalization, other clinical outcomes and quality of life have not been evaluated. The long-term effect of IPAA therapy remains unclear. 

      IPAA supplementation decreased bicarbonate levels,  and mild acidosis may occur in some patients,  although it is readily treatable. In diabetic patients on PD with uncontrolled hyperglycemia, substituting amino acid for glucose in PD solutions may serve as an immediate strategy for glycemic control.

    • Potential Costs Associated with Application

      The cost of dialysate protein-energy supplementation should be considered before recommending to a patient.

    • Recommendation Narrative

      Protein-energy wasting is common among patients on maintenance PD, and is associated with increased morbidity and mortality (Park et al 2006).  Inflammation, acidosis, insulin resistance, insufficient dietary intakes of protein and energy as a result of anorexia, and peritoneal losses of proteins and amino acids contribute to protein-energy wasting (Tjiong et al 2008).  Intraperitoneal amino acids (IPAA) supplementation was introduced to compensate for low protein intake and protein losses.  Substituting amino acids for glucose in PD solutions should increase the amino acid intake and decrease the net amino acid losses of the patient, thereby increasing the net intake of protein precursors (Kopple et al 1995).  IPAA supplementation may also reduce the infused carbohydrate load, thereby reducing the risk of hyperglycemia and the tendency to hypertriglyceridemia (Kopple et al 1995). 

      Detailed Justification
      This evidence review included three studies that examined the effect of IPAA supplementation on nutritional status in malnourished PD patients, including two RCTs (Jones et al 1998, Li et al 2003) and one non-randomized crossover trial (Misra et al 1997).  In the two RCTs (Jones et al 1998, Li et al 2003),  results were compared between those receiving traditional 1.5% dextrose dialysate vs those who replaced one to two daily exchanges of 1.5% dextrose dialysate with 1.1% amino acid dialysate.  Study durations ranged from 3 months (Jones et al 1998) to 3 years (Li et al 2003).  In the non-randomized crossover trial, Misra, et al. utilized the same study design in which the participants were assigned to each exposure (amino acid dialysate for one exchange/day or dextrose dialysate only) for 6 months (Misra et al 1997). In all of these studies, PD patients demonstrated some level of malnutrition.  In Misra, et al,  the majority of patients were presented with hypoalbuminemia; in Li, et al,  all patients were malnourished; and in Jones, et al,  participants were mildly to moderately malnourished.

      Anthropometric Measurements and Laboratory Measures of Nutritional Status
      Two RCTs examined the effect of IPAA therapy on anthropometric measurements in malnourished PD patients (Jones et al 1998, Li et al 2003). MAMC, triceps skinfold measurements and FM were maintained at 3 months and 3 years in both IPAA and dextrose dialysate groups. The results from these studies indicated that substituting amino acid dialysate for dextrose dialysate had no effect on anthropometric measurements. 

      Two RCTs (Jones et al 1998, Li et al 2003) and one non-randomized crossover trial (Misra et al 1997) examined the effect IPAA supplementation on albumin, pre-albumin, and transferrin levels in malnourished PD patients.  One randomized-controlled trial evaluated the effect of IPAA supplementation on total protein level (Jones et al 1998).  The findings from these studies concluded that substituting amino acid dialysate for dextrose dialysate in malnourished PD patients did not affect albumin, pre-albumin, transferrin, and total protein levels compared to those receiving dextrose dialysate only.

      Electrolyte Levels (Phosphorus/Phosphate, Bicarbonate, and Potassium Levels)
      One RCT (Jones et al 1998) and one non-randomized crossover trial (Misra et al 1997) examined the effect of IPAA supplementation on electrolyte levels in malnourished PD patients.  The findings from these studies suggested that substituting amino acid dialysate for dextrose dialysate in malnourished PD patients decreased their phosphate and bicarbonate levels, but the effect on potassium levels was unclear.   

      Jones, et al. showed that serum potassium and phosphate levels decreased significantly in IPAA group and levels were different between groups at 3 months (p<0.05 for each measure) (Jones et al 1998).  In contrast, Misra, et al. showed no within-group changes in potassium, phosphate or bicarbonate levels in either IPAA or dextrose dialysate groups (Misra et al 1997).  However, when averaged across time, patients receiving IPAA therapy had lower mean phosphate (p=0.018) and bicarbonate levels (p=0.002).  In secondary analysis, the IPAA groups in Jones, et al. and Misra, et al. demonstrated a mean difference (95% CI) of -0.50 (-0.87, -0.13) mEq/L in potassium and -1.10 (-1.43, -0.77) mmol/L in bicarbonate levels respectively when compared to the dextrose dialysate group.  In pooled analysis, there was a mean difference (95% CI) of -0.55 (-0.70, -0.41) mg/dL in phosphate levels in the IPAA group compared to the dextrose dialysate group.

      Dietary Intake (Protein and Energy Intake)
      One randomized-controlled trial examined the effect of IPAA supplementation on total and oral protein and energy intakes in malnourished PD patients (Li et al 2003).  Compared to baseline intake levels, total protein intake increased in the IPAA group beginning at 6 months and continuing until 3 years (p=0.002 for each measure), but there was no significant difference between IPAA and dextrose dialysate groups.  Compared to baseline intake, total energy intake increased in the IPAA group at 6 months (p<0.001) and 3 years (p=0.002), but it decreased in the dextrose dialysate group (p<0.001), though there were no significant differences between groups.  Similar results were observed for oral and peritoneal energy intake only.  nPNA (nPCR) increased in the IPAA group at 3 years, but decreased in the dextrose dialysate group, and values were significantly different between groups at 3 years (p<0.001). 

    • Recommendation Strength Rationale

      The evidence supporting this recommendation statement is based on Grade III/Grade C level of evidence.

    • Minority Opinions

      Consensus reached.