Quick Links

Recommendations Summary

CKD: Macronutrients: Oral, Enteral and Intradialytic Parenteral Nutrition Supplementation (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: Oral Protein-Energy Supplementation for CKD 3-5D

    In adults with CKD 3-5D at risk of or with protein-energy wasting, we suggest a minimum of a 3-month trial of oral nutritional supplements to improve nutritional status if dietary counselling alone does not achieve sufficient energy and protein intake to meet nutritional requirements (2D).

    Rating: Weak
    Conditional

    CKD: Oral Protein-Energy Supplementation for Post-Transplant

    In adults with CKD posttransplantation at risk of or with protein-energy wasting, it is reasonable to consider a minimum of a 3-month trial of oral nutritional supplements to improve nutritional status if dietary counselling alone does not achieve sufficient energy and protein intake to meet nutritional requirements (OPINION).

    Rating: Consensus
    Conditional

    CKD: Enteral Nutrition Supplementation

    In adults with CKD 1-5D, with chronically inadequate intake and whose protein and energy requirements cannot be attained by dietary counselling and oral nutritional supplements, it is reasonable to consider a trial of enteral tube feeding (OPINION).

    Rating: Consensus
    Conditional

    CKD: Total Parenteral Nutrition (TPN) and Intradialytic Parenteral Nutrition (IDPN) Protein-Energy Supplementation

    In adults with CKD with protein-energy wasting, we suggest a trial of total parenteral nutrition (TPN) for CKD 1-5 patients and IDPN for CKD 5D on MHD patients, to improve and maintain nutritional status if nutritional requirements cannot be met with existing oral and enteral intake (2C).

    Rating: Weak
    Conditional

    • Risks/Harms of Implementing This Recommendation

      Energy-dense and low-electrolyte, renal-specific oral nutritional supplements (ONS) may be necessary to increase protein and energy intake and avoid fluid and electrolyte derangements. Gastrointestinal side effects can influence adherence to ONS and extended periods of monotonous supplementation can lead to flavor and taste fatigue as well as non-adherence to the prescribed ONS. Therefore, regular monitoring and evaluation during the supplementation period is crucial and adjustments to the ONS prescription may be necessary to improve adherence and optimize effectiveness.

    • Conditions of Application

      A complete nutritional assessment should be performed prior to considering ONS and should be repeated at regular intervals during the supplementation period.

      IDPN therapy does not alter patient’s eating behavior, nor does it encourage healthy eating habits. Patients on IDPN may suffer from time-limitation due to MHD frequency and duration. Because IDPN is usually given for 4 hours during dialysis thrice weekly, it may not provide sufficient calories and protein to meet long-term nutritional requirements.  TPN is usually administered on a daily basis. The potential of IDPN to meet target protein and energy requirements in MHD patients mainly depends on the actual difference between these targets and spontaneous dietary intakes via ONS or dietary counselling.  If the difference can be met by the IDPN regimen, the workgroup felt that IDPN should be considered in conjunction with ONS or dietary counselling.

      This evidence review suggested that that IDPN offers no further benefit over ONS. It was postulated that markers of nutritional status improved irrespective of the route of nutrient administration as long as dietary protein and energy targets are met (Cano et al 2007).  However, a direct comparison between IDPN and ONS was lacking, this would only imply that ONS is equally effective as IDPN when oral intake is possible. Since ONS was included in the intervention arm as well, the inferiority of IDPN over ONS cannot be confirmed.

      A recently published a RCT investigating the effect of IDPN therapy on pre-albumin and other biochemical and clinical nutritional markers in malnourished MHD patients (Marsen et al 2017),  demonstrated that IDPN therapy increased pre-albumin levels and was superior to nutritional counselling after 16 weeks.  This study was not included in this evidence review because the date of publication was beyond the cut-off time for study inclusion. In this study, patients randomized to the intervention group received standardized nutritional counselling plus IDPN three times weekly for 16 weeks. There were no within-group changes and between-group differences at week 16 in other clinical and biochemical nutritional markers (BMI, albumin, transferrin, PCR, phase angle alpha, and SGA).

      Implementation Considerations

      • ONS should be prescribed two to three times daily and patients should be advised to take ONS preferably 1 hour after meals rather than as a meal replacement in order to maximize benefit.
      • Monitored in-center provision of high-protein meals or ONS during MHD may be a useful strategy to increase total protein and energy intake. Many of the perceived negative effects of intradialytic feeding such as postprandial hypotension, aspiration risk, infection control and hygiene, as well as diabetes and phosphorus control can be avoided with careful monitoring
      • ONS prescription should take into account patient preference. The acceptability of ONS in terms of appearance, smell, taste, texture, and type of preparation (milkshake type, juice type, pudding type, protein/energy bar, or fortification powder) should be carefully considered.
      • Energy-dense and low-electrolyte, renal-specific ONS may be necessary to increase protein and energy intake and avoid fluid and electrolyte derangements.
      • Increased risk of infectious complications and the high cost of IDPN are the greatest barriers for regular use of IDPN.
      • MHD patients meeting all of the following three criteria may benefit from IDPN therapy1) evidence of protein-energy malnutrition and inadequate dietary protein and/or energy intake; 2) inability to administer or tolerate adequate oral nutrition, including food supplements or enteral feeding; and 3) protein and energy requirements can be met when IDPN is used in conjunction with oral intake or enteral feeding.
      • IDPN therapy should not be considered as a long-term approach of nutritional support.  It should be discontinued and ONS should be attempted as soon as improvements in nutritional status are observed and patients are capable of using oral or enteral route.
      • If IDPN therapy in conjunction with oral intake does not achieve the nutritional requirements of the patient, or the gastrointestinal tract is malfunctioned, then total parenteral nutrition (TPN) given on a daily basis should be considered.

      Monitoring and Evaluation
      Gastrointestinal side effects can influence adherence to ONS (Akpele et al 2004) and extended periods of monotonous supplementation can lead to flavor and taste fatigue as well as non-adherence to the prescribed ONS. Therefore, regular monitoring and evaluation during the supplementation period is crucial and adjustments to the ONS prescription may be necessary to improve adherence and optimize effectiveness. Nutritional status should be monitored regularly throughout the supplementation period in order to evaluate effectiveness of ONS.

      Ongoing monitoring and evaluation of nutritional status during IDPN therapy is necessary. Serum glucose should be closely monitored during and post MHD.  In the case of insulin requirement, the use of subcutaneous short-acting insulin analogs should be chosen to avoid post-dialytic hypoglycemia. The ultrafiltration rate should be adjusted to remove the extra fluid provided by IDPN.

    • Potential Costs Associated with Application

      The cost of nutrition supplements should be considered before recommending to a patient.

    • Recommendation Narrative

      Protein-energy wasting (PEW) is common among patients with CKD, especially those undergoing maintenance dialysis therapy,  and is associated with increased morbidity and mortality. The etiology of PEW in patients with CKD is complex and multifactorial, and includes reduced energy and protein intake resulting from anorexia and dietary restrictions, inflammation, hypercatabolism, protein losses during dialysis, metabolic acidosis, uremic toxicity, and the presence of comorbid conditions. As a result, patients with CKD may develop an imbalance between dietary intake and nutritional requirements. Indeed, many patients with CKD consume less protein and energy than their recommended intakes even when individualized dietary counselling is provided by a renal dietitian.

      When dietary counselling alone proves insufficient to bridge the gap between protein-energy intake and the target requirements in patients with CKD, provision of oral nutritional supplements (ONS) is often the next appropriate step to prevent and treat PEW. Therefore, it is important to establish the effectiveness of ONS on nutritional status, clinical outcomes and quality of life in patients with CKD.

      Although feeding through the gastrointestinal route should be the preferred choice of nutritional supplementation, feeding through the parenteral route (i.e. total parenteral nutrition), may be a safe and convenient approach for patients who cannot tolerate oral or enteral administration of nutrients (Ikizler et al 2013). In MHD patients, utilization of the hemodialysis access for TPN provides a significant advantage by eliminating the need for an additional permanent venous catheter placement. Since HD access is routinely utilized for the HD procedure. TPN can be conveniently administered during HD via the dialysis tubing. This type of TPN administration is called intradialytic parenteral nutrition (IDPN).

       Detailed Justification
      This evidence review included fifteen clinical trials, twelve of which were RCTs and three NRCTs. Most of the studies examined the effect of ONS in patients on maintenance hemodialysis (MHD). However, Moretti et al included patients on MHD and peritoneal dialysis (PD) with the results merged; Gonzalez-Espinoza et al and Teixido-Planas et al studied patients on PD only; and Wu et al studied patients with CKD, stages 3-4. No studies were performed in patients with CKD with kidney allografts. Most of the studies examined the effect of oral protein-energy or protein-based ONS using commercial products. However, Allman et al used a glucose-polymer ONS and Wu et al used a non-protein calorie ONS. Four studies used renal-specific protein-energy ONS. A major drawback of the literature was the limited use of a placebo group, though most studies did include a comparator group which was defined as participants not receiving ONS or receiving only nutritional counselling. Study durations ranged from 12 weeks to 13½ months. Seven of the RCTs included participants with some level of malnutrition at baseline. In contrast, five studies did not actively enroll malnourished patients.Of the NRCTs Sezer et al enrolled malnourished patients as defined by serum albumin or weight loss, Cheu et al enrolled patients with hypoalbuminemia, and Scott et al did not actively recruit patients with malnutrition.

      Mortality, Hospitalizations, and Quality of Life
      One NRCT examined the effect of ONS on mortality in 276 patients on MHD who received for ONS for a low serum albumin versus 194 similar patients who refused ONS or in whom treatment was deemed inappropriate (Cheu et al 2013). No difference in mortality [HR (95% CI); 0.70 (0.36,  1.35)] was noted over a median duration of 13.5 months.

      Two RCTs (Wilson et al 2001, Moretti et al 2009) and one NRCT (Cheu et al 2013) evaluated the effect of ONS on hospitalization over a period of 6 to 13.5 months in patients on MHD or PD. A pooled analysis of the two RCTs (Moretti et al 2009, Cheu et al 2013) found no significant difference in odds of hospitalization by group assignment, but a NRCT (Cheu et al 2013) reported a 34% reduction in hospitalization risk [0.66 (0.50, 0.85)] by 12 months in patients receiving ONS compared to controls.

      Three studies (two RCTs (Calegari et al 2011, Fouque et al 2008) and one NRCT (Scott et al 2009)) each of three months’ duration examined the effect of ONS on quality of life (QOL) measures in patients on MHD. One RCT (Calegari et al 2011) and one NRCT (Scott et al 2009) reported that patients receiving general (Calegari et al 2011) or renal-specific (Scott et al 2009) protein-energy ONS had higher QOL scores in the domains of physical functioning (Caleari et al 2011, Scott et al 2009) and bodily pain (Calegari et al 2011) compared to receiving dietary advice only (Calegari et al 2011) or no supplementation (Scott et al 2009),  but another RCT (Fouque et al 2008) reported that renal-specific protein-energy ONS did not influence QOL scores in any domain. A pooled analysis of the two RCTs (Calegari et al 2011, Scott et al 2009) found that ONS did not significantly influence bodily pain, physical functioning, or general health QOL domain scores.

      CKD Progression
      A RCT (Wu et al 2013) conducted for 24 weeks examined the effect of an energy-based ONS on progression of CKD in 109 patients with CKD 3-4 who were following a low-protein diet. While no difference in serum creatinine or eGFR was observed between ONS and controls, there was a comparative reduction in proteinuria in the ONS arm (p<0.05).

      Composite Nutritional Scores & Biochemical Markers of Nutritional Status
      A 3-month RCT in 18 patients on MHD examined the effect of a food-based ONS on Subjective Global Assessment (SGA) scores (Calegari et al 2011). Authors describe a significantly greater SGA improvement in patients receiving ONS compared to patients receiving nutritional guidance only.  One NRCT found that ONS over a six-month period did not influence the Malnutrition Inflammation Score (MIS) as compared to dietary advice (Sezer et al 2014).

      Fifteen studies (twelve RCTs (Calegari et al 2011, Wilson et al 2001, Fouque et al 2008, Allman et al 1990, Bolasco et al 2011, Tomayko et al 2015, Hiroshige et al 2001,   Moretti et al 2009, Conzalez-Espinoza et al 2005, Teixido-Planas et al 2005, Wu et al 2013) and three NRCTs (Sezer et al 2014, Cheu et al 2013, Scott et al 2009) examined the effect of ONS on serum albumin in patients with 3-5D. These included eleven in patients on MHD 3 to 13.5 months’ duration, one RCT (Moretti et al 2009) in patients on MHD and PD of 6 months’ duration, two RCTs (Gonzalez-Espinoza et al 2005, Teixido-Planas et al 2005) in patients on PD of 6 months’ duration, and one (Wu et al 2013) in patients with CKD 3-4 of 24 weeks’ duration. Overall, the literature suggested that protein-energy ONS modestly improved serum albumin levels though the results should be interpreted with caution. A pooled analysis of 11 studies (Sezer et al 2014, Calegari et al 2011, Fouque et al 2008, Allman et al 1990, Bolasco et al 2011, Hung et al 2009, Moretti et al 2009, Gonzalez-Espinoza et al 2005, Teixido-Planas et al 2005, Wu et al 2013, Scott et al 2009) that included patients with CKD 3-5D found that ONS modestly improved serum albumin as compared to controls [mean difference (95% CI); 0.121 (0.006, 0.236) g/dL]. However, a subgroup analysis found the effect to be significant only when using protein-energy ONS (Sezer et al 2014, Calegari et al 2011, Fouque et al 2008, Hung et al 2009,   Teixido-Planas et al 2005, Scott et al 2009) [mean difference (95% CI); 0.16 (0.08, 0.24) g/dl] and not energy (Allman et al 1990, Wu et al 2013) or protein-based (Bolasco et al 2011, Moretti et al 2009, Gonzalez-Espinoza et al 2005) supplements. Heterogeneity of results in the pooled analysis was high (I2=68.3%, p<0.001) so results should be interpreted cautiously.

      One RCT (Fouque et al 2008) in 86 patients on MHD reported that ONS did not influence serum pre-albumin levels as compared to dietary advice. Two RCTs of 3-6 months’ duration in patients on MHD reported conflicting effects of ONS on total protein, perhaps related to type of ONS (Allman et al 1990, Bolasco et al 2011).The first study of 30 patients reported a positive effect on total protein using an amino acid-based ONS (Bolasco et al 2011) while a second of 21 patients found no effect of a 6-month energy-based ONS intervention (Allman et al 1990). Two studies (an RCT (Allman et al 1990) and an NRCT (Scott et al 2009) in patients on MHD of 3-6 months’ duration found no effect of ONS on serum transferrin, either individually or in a pooled analysis.

      Anthropometric Measurements
      The effect of ONS on anthropometric indices varied in large part according to the type of ONS used, with the greatest effects being seen in one study (Allman et al 1990) that used an energy based ONS

      Body Mass Index (BMI): Seven studies (six RCTs (Calegari et al 2011, Fouque et al 2008, Allman et al 1990, Bolasco et al 2011, Hung et al 2009, Gonzalez-Espinoza et al 2005) and one NRCT (Sezer et al 2014)) evaluated the effect of ONS on BMI over a 3-6-month period. Six of the studies were conducted in patients on MHD (Sezer et al 2014, Calegari et al 2011, Fouque et al 2008, Allman et al 1990, Bolasco et al 2011, Hung et al 2009) and one in patients on PD (Gonzalez-Espinoza et al 2005). A pooled analysis demonstrated no overall effect of ONS on BMI though the study using an energy-based ONS noted a rise in BMI (Allman et al 1990). Overall, the heterogeneity was moderate (I2=49.8%, p=0.06).

      Body Weight: Six studies (5 RCTs and 1 NRCT) investigated the effect of ONS on body weight over 3 to 6 months in patients on MHD (Allman et al 1990, Bolasco et al 2011, Tomayko et al 2015, Scott et al 2009),  PD (Teixido-Planas et al 2005),  and with CKD 3-4 (Wu et al 2013). Overall, ONS was linked to increased body weight but mainly in patients on MHD consuming an energy-based supplement. However, one RCT in patients on PD that used a protein-based ONS reported increased body weight (Teixido-Planas et al 2005). A pooled analysis of all six studies (Allman et al 1990, Bolasco et al 2011, Tomayko et al 2015, Teixido-Planas et al 2005, Wu et al 2013, Scott et al 2009) found higher body weight in the ONS group compared to the control arm [mean (95% CI); 2.77 (1.19, 4.36) kg] in patients with CKD 3-5D. However, the difference was mainly driven by energy based ONS in patients on MHD.

      Dialysis Target Weight: Four studies (3 RCTs (Hiroshige et al 1998, Calegari et al 2011, Fouque et al 2008) and 1 NRCT (Sezer et al 2014)) in patients on MHD (Sezer et al 2014, Hiroshige et al 1998, Fouque et al 2008),  examined the effect of ONS on dialysis target weight over a 3 to 6-month period. Overall, no effect of ONS on target weight was observed, though one NRCT (Sezer et al 2014) reported an increase in target weight using a renal-specific protein-energy ONS (Sezer et al 2014) as did one RCT (Hiroshige et al 2001) using a protein-based ONS. A pooled analysis of three studies (Sezer et al 2014, Calegari et al 2011, Fouque et al 2008) found no overall effect. Hiroshige, et al. reported results in a figure and could not be included in pooleanalysis.

      Lean Body Mass/Fat Free Mass/Muscle MassSeven trials (six RCTs (Calegari et al 2011, Allman et al 1990, Bolasco et al 2011, Tomayko et al 2015, Hiroshige et al 2001, Teixido-Planas et al 2005) and NRCT (Sezer et al 2014)) in patients on MHD (Sezer et al 2014, Calegari et al 2011, Allman et al 1990, Bolasco et al 2011, Tomayko et al 2015, Hiroshige et al 2001) or PD (Teixido-Planas et al 2005) studied the effect of ONS on markers of lean mass over 3 to 6 months. Overall, ONS increased LBM or fat free mass only in patients on MHD who received an energy-based ONS. In patients on MHD, the effect of protein-based ONS on LBM was mixed. In a pooled analysis of 6 studies (Sezer et al 2014, Calegari et al 2011,  Allman et al 1990, Bolasco et al 2011, Tomayko et al 2015, Teixido-Planas et al 2005) ONS was associated with a significant increase in lean body mass or fat free mass [mean difference (95% CI); 1.18 (0.16, 2.20) kg] compared to the control arm, but a subgroup analysis found the effect to be significant only in patients on MHD using energy-based ONS.

      Body FatSeven studies (six RCTs (Calegari et al 2011,  Allman et al 1990, Bolasco et al 2011, Tomayko et al 2015, Hung et al 2009, Hiroshige et al 2011) and one NRCT (Sezer et al 2014)) in patients on MHD evaluated the effect of ONS on body fat over a period of 3 to 6 months. A pooled analysis of six studies (Sezer et al 2014,  Calegari et al 2011,  Allman et al 1990, Bolasco et al 2011, Tomayko et al 2015, Hung et al 2009) reported no overall effect of ONS on body fat mass though subgroup analyses demonstrated that energy (Allman et al 1990) and protein-energy (Sezer et al 2014, Calegari et al 2011, Hung et al 2009) based ONS significantly increased body fat mass compared to controls, but protein-based ONS had no effect.

      Skinfold Measurements: Five studies (four RCTs (Calegari et al 2011, Allman et al 1990, Gonzalez-Espinoza et al 2005,   Teixido-Planas et al 2005) and one NRCT (Sezer et al 2014) in patients with CKD on MHD (Sezer et al 2014, Calegari et al 2011, Allman et al 1990) or PD (Gonzalez-Espinoza et al 2005,   Teixido-Planas et al 2005) examined the effect of ONS on skinfold measurements over a 3 to 6-month period. A pooled analysis of 4 studies (Sezer et al 2014, Calegari et al 2011,  Gonzalez-Espinoza et al 2005,   Teixido-Planas et al 2005) reported that ONS significantly increased skinfold measurements [mean difference (95% CI); 3.91 (0.93, 6.90) mm] compared to dietary counselling or no supplementation, but this effect was significant only in patients on MHD using energy based ONS.

      Arm or Muscle CircumferenceFour RCTs in patients on MHD (Calegari et al 2011, Allman et al 1990) or PD (Gonzalez-Espinoza et al 2005,   Teixido-Planas et al 2005) evaluated the effect of ONS on arm or muscle circumference over a 3 to 6-month period. None of the studies showed any effect.

      Dietary Intake
      Protein: Ten studies (nine RCTs (Calegari et al 2011, Fouque et al 2008, Allman et al 1990, Bolasco et al 2011, Moretti et al 2009, Wu et al 2013, Gonzalez-Espinoza et al 2005, Teixido-Planas et al 2005, Hiroshige et al 2001) and one NRCT (Sezer et al 2014)) examined the effect of ONS on protein intake as estimated by nPCR/nPNA, 24-hour dietary recall or multiple-day food records with study durations of three to six months. Overall, protein-based supplements (AA (Bolasco et al 2011) or BCAA (Hiroshige et al 2011) increased reported protein intake and nPCR in patients on MHD and PD but energy (Allman et al 1990, Wu et al 2013)  or protein-energy supplements did not influence either marker in patients with CKD 3-5D. A pooled analysis of seven studies (Sezer et al 2014,  Calegari et al 2011, Fouque et al 2008,  Bolasco et al 2011, Moretti et al 2009,  Gonzalez-Espinoza et al 2005, Teixido-Planas et al 2005) found that ONS significantly increased nPCR in patients on dialysis [standardized mean difference (95% CI); 0.29 (0.04, 0.53)], suggesting a potentially clinically relevant effect. However a subgroup analysis found the effect to be significant only in persons receiving protein-based (Bolasco et al 2011, Moretti et al 2009,  Gonzalez-Espinoza et al 2005) but not protein-energy based ONS (Sezer et al 2014, Calegari et al 2011, Fouque et al 2008,  Teixido-Planas et al 2005). Similar results were noted in a pooled analysis of three studies (Fouque et al 2008,  Gonzalez-Espinoza et al 2005, Wu et al 2013) examining the effects of ONS on reported protein intake where ONS increased reported protein intake only in one study that supplemented egg albumin protein (Gonzalez-Espinoza et al 2005).

      Energy: Six RCTs231, 232, 235, 237, 239, 242 with study duration of 3 to 6 months examined the effect of ONS on energy intake in patients on MHD, 231, 232, 235, 242 on  PD, 237 and with CKD, stages 3-4.239 Overall ONS raised energy intake though the effect was limited to patients on MHD receiving renal-specific protein-energy ONS. Four out of five studies in patients on dialysis reported that ONS increased energy intake.231, 232, 235, 237, 242 However, a subgroup analysis found the effect to be significant only for patients on MHD receiving protein-energy ONS, 231, 235 but not receiving protein-237 or energy-based239 ONS alone. The only study in patients with CKD 3-4 found no improvement in energy intake using a non-protein calorie ONS (Wue et al 2013).

      Phosphorus and Calcium: An RCT of 3 months’ duration in patients on MHD found no effect on phosphorus or calcium intake (Fouque et al 2008).

      Other Biochemical Markers (CPR, anemia indices, electrolyte levels)
      Seven studies (six RCTs (Calegari et al 2011, Fouque et al 2008, Allman et al 1990,  Bolasco et al 2011, Tomayko et al 2015, Hung et al 2009, Wu et al 2013) and one NRCT (Sezer et al 2014) of 3-6 months’ duration in patients on MHD (Calegari et al 2011,  Calegari et al 2011, Fouque et al 2008, Bolasco et al 2011, Tomayko et al 2015, Hung et al 2009, Sezer et al 2014) and CKD 3-4 (Wu et al 2013) found no effect of ONS on CRP. Seven studies (five RCTs (Calegari et al 2011,  Allman et al 1990,  Bolasco et al 2011, Tomayko et al 2015, Gonzalez-Espinoza et al 2005) and two NRCT (Sezer et al 2014, Bolasco et al 2011)) in patients on MHD (Calegari et al 2011, Allman et al 1990,  Bolasco et al 2011, Tomayko et al 2015, Sezer et al, Bolasco et al 2011) or PD (Gonzalez-Espinoza et al 2005) examined the effect of ONS on markers of anemia over a 3 to 6-month period. Overall, ONS had no effect on these markers. Five studies (four RCTs (Calegari et al 2011, Tomayko et al 2015, Gonzalez-Espinoza et al 2005, Wu et al 2013) and one NRCT (Scott et al 2009) examined the effect of ONS on serum calcium, phosphate, and potassium levels over 3 to 6 months. Three of the trials were in patients on MHD (Calegari et al 2011, Tomayko et al 2015, Scott et al 2009) one was in patients on PD (Gonzalez-Espinoza et al 2005), and one was in patients with CKD 3-4 (Wu et al 2013). None of the studies found any effect on ONS on these electrolytes. Five studies (four RCTs (Allman et al 1990, Hung et al 2009,  Gonzalez-Espinoza et al 2005, Wu et al 2013) and one NRCT (Sezer et al 2014) examined the effect of ONS on plasma lipids over 3 to 6 months.

      IDPN
      This evidence review encompassed three studies that examined the effects of IDPN on nutritional status and clinical outcomes in MHD patients, including one NRCT (Hiroshige et al 1998) and two RCTs (Cano et al 2007, Toigo et al 1989).  In all these studies, participants were malnourished. In Hiroshige, et al,  participants in the intervention group received dietary counselling from an RDN and an IDPN infusion of 200 ml 50% dextrose, 200 ml 7.1% EAAs, and 200 ml 20% lipid emulsion, providing 2400 kcal and 42.3 g amino acid for one year.  Results were compared to a group receiving dietary counselling only (control group). In Cano, et al, all participants were given an oral nutritional supplements (ONS) providing 25 g/protein/day and 500 kcal/day for one year, and the intervention group additionally received IDPN to meet target ranges of 30 to 35 kcal/day and 1.2 g/protein/kg/day; and included a standard lipid emulsion of 50% glucose, 50% non-protein energy supply, and a standard amino acid solution. In Toigo, et al, participants in the intervention group were given (EAAs) IV formula for 6 months.  Results were compared to participants in the intervention group where they received an isonitrogenous standard formula containing both non-essential amino acids (NEAAs) and EAAs for 6 months.  Both groups simultaneously received 500ml of 10% glucose.  Participants were followed up for an additional 6 months.

      Mortality and Hospitalization
      Only one study examined and found no effect of IDPN on mortality and hospitalization.  In Cano, et al,  statistical comparisons were not provided but the authors described no significant differences in mortality or hospitalization events between ONS only and IDPN with ONS groups. 

      Anthropometric Measurements
      The three studies examined the effect of IDPN therapy on anthropometric measurements in malnourished MHD patients (Hiroshige et al 1998, Cano et al 2007, Toigo et al 1989).  The findings from these studies indicated that IDPN, in combination with dietary counselling (Hiroshige et al 1998) or ONS (Cano et al 200),  increased BMI (Hiroshige et al 1998, Cano et al 2007),  dry body weight (Hiroshige et al 1998),  skinfold measurements (Hiroshige et al 1998),  and MAMC (Hiroshige et al 1998) compared to dietary counselling only.  However, similar improvement in BMI was observed when adequate and comparable protein and energy were given to patients receiving ONS only (Cano et al 2007).  Compared to a standard IDPN formulation of both EAAs and NEAAs, an IDPN formulation with EAAs did not affect % desirable body weight, skinfold measurements, and AMA (Toigo et al 1989).   

      Laboratory Markers of Nutritional Status (albumin, pre-albumin, transferrin, and nPCR)
      Three studies (Hiroshige et al 1998, Cano et al 2007, Toigo et al 1989) examined the effect of IDPN on laboratory markers of nutritional status in malnourished MHD patients.  The results from these studies concluded that IDPN in conjunction with dietary counselling or ONS increased albumin (Hiroshige et al 1998, Cano et al 2007),  pre-albumin (Cano et al 2007) or transferrin levels (Hiroshige et al 1998),  but similar improvements in albumin and pre-albumin levels were observed when adequate and comparable protein and energy were provided to patients receiving ONS only (Cano et al 2007). Compared to a standard IDPN formulation of both EAAs and NEAAs, an IDPN formulation with EAAs only did not affect albumin and transferrin levels (Toigo et al 1989).   

      Other Laboratory Markers (Inflammation (CRP); Hemoglobin, Lipid Profile)
      One study evaluated and found no effect of IDPN on inflammation in malnourished hemodialysis patients. Cano, et al.reported no change in CRP levels in either ONS only or IDPN+ONS groups, although data was not provided. One study examined and found no effect of IDPN therapy with EAAs only vs standard IDPN formulation with both EAAs and NEAAs on hemoglobin levels in malnourished MHD patients after 6 months (Toigo et al 1989). 

      Two studies examined the effect of IDPN on lipid profile (Hiroshige et al 1998, Cano et al 2007). The results from these studies showed that combining IDPN with dietary counselling or ONS did not affect total cholesterol or triglyceride levels.  

      Dietary Intake (Energy and Protein Intake)
      Two studies (Hiroshige et al 1998, Cano et al 2007) examined the effect of IDPN on dietary intake in malnourished MHD patients.  The findings from these studies showed inconclusive effects of IDPN on dietary energy and protein intakes.   

    • Recommendation Strength Rationale

      The evidence supporting these recommendations on Grade III /Grade D evidence and Consensus/expert opinion.

    • Minority Opinions

      Consensus reached.