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Recommendations Summary

CKD: Nutrition Assessment with Laboratory Measurements (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: Single Biomarker Measurements

    In adults with CKD stages 1-5D or posttransplantation, biomarkers such as normalized protein catabolic rate (nPCR),   serum albumin and/or serum prealbumin (if available) may be considered complementary tools to assess nutritional status. However, they should not be interpreted in isolation to assess nutritional status as they are influenced by non-nutritional factors (OPINION).

    Rating: Consensus

    CKD: Serum Albumin Levels

    In adults with CKD 5D on MHD, serum albumin may be used as a predictor of hospitalization and mortality, with lower levels associated with higher risk (1A).

    Rating: Strong

    • Risks/Harms of Implementing This Recommendation

      There are no potential risks or harms associated with the application of the guideline for serum albumin in adult patients with CKD on maintenance dialysis.

    • Conditions of Application

      The guideline for serum albumin applies to all adult patients with CKD on maintenance dialysis. The biochemical markers must be obtained pre-dialysis for maintenance dialysis patients.

    • Potential Costs Associated with Application

      There are no obvious costs associated with the application of this guideline.

    • Recommendation Narrative

      Assessments of nutritional status in patients with CKD have traditionally relied upon biochemical or other related calculated-indices such as serum albumin, prealbumin, and nPCR (normalized protein catabolic rate)/nPNA (normalized protein nitrogen appearance) as diagnostic tools. Albumin is a major circulating protein that plays a number of biologic roles, such as maintaining osmotic pressure and transporting a variety of molecules. Serum prealbumin, also known as transthyretin, is another circulating protein produced by the liver with a shorter half-life than albumin, it is therefore more sensitive to rapid changes in nutritional status. nPCR (or the more recent nomenclature nPNA) is a common tool used to estimate protein intake and is calculated using the intradialytic rise in the blood urea nitrogen in MHD patients and from urinary urea from 24-hour urine collection in non-dialyzed CKD patients. The advantages of such markers include the fact that they are easily quantifiable and available for each patient. However, these markers are known to be heavily influenced by inflammation, illness, liver failure, volume expansion and urinary or dialysate protein losses (or in the case of nPCR/nPNA, protein balance and other factors). In fact, serum albumin is one of the best predictors of illness or death in patients with ESRD. In light of this, their utility in assessing nutritional status has been re-evaluated in recent years.  Existing data suggest that such markers are not sufficiently reliable or valid to use in isolation for assessing nutritional status.  Instead, it should be used as part of a more comprehensive and inclusive evaluation as used for screening purposes.   

      Detailed Justification

      Serum Albumin
      Sixteen observational studies that compared serum albumin concentration to other methods used to assess nutritional status, including twelve studies with MHD patients, two studies with PD patients, and two studies with both MHD and PD patients were included in this review

      Maintenance Hemodialysis Patients:
      Among the maintenance hemodialysis (MHD) studies, one was a prospective cohort study (de Roij et al 2015),  two were retrospective cohort studies (Araujo et al 2006, Campbell et al 2010),  seven were cross-sectional studies (Aatif et al 2013, Beberashvilli et al 2009, Kadiri et al 2011, Jones et al 2002, Malgorzewicz et al 2008, Molfinoet al 2013, Yelken et al 2010). Two studies were diagnostic validity or reliability studies (Mancini et al 2003, Gurreebun et al 2007).

      Gurreebun, et al. determined that serum albumin concentration was a sensitive method for identifying patients at risk of PEW defined by the 7-point SGA score. In a study by Mancini, et al., albumin independently predicted bioimpedance vector analysis (BIVA) in patients with normal values of other nutritional indexes, but the association was not significant in with patients with worse nutritional values. Araujo, et al. demonstrated that serum albumin concentration <3.5 g/dL were associated with higher odds of mortality over 10 years [OR (95%CI) = 2.34 (1.33-4.10); p=0.002]. Campbell, et al. found that low albumin concentration (<38 g/L) were significantly associated with higher mortality and morbidity (length of hospital stay), but there was no adjustment for comorbidities. De Roij van Zuijdewijn, et al. determined that albumin concentration predicted all-cause mortality and was the most predictive of 8 other nutrition measures.

      In Yelken, et al., serum albumin concentration were significantly correlated with high sensitivity C-reactive protein (hsCRP), tricep skinfold, mid arm circumference (MAC), and mid-arm muscle circumference (MAMC).  Serum albumin concentration were associated with nPCR and inflammatory markers (Jones et al 2002,  Molfinoet al 2013); BMI (Kadiri et al 2011); 7-point SGA score (Malgorzewicz et al 2008); and lean tissue index, but not fat tissue index from bioimpedance spectroscopy (Aatif et al 2013) BMI and FM (Beberashvili et al 2009).

      Peritoneal Dialysis Patients 
      Of the two studies in PD, one was a prospective cohort study (Churchill et al 1996) and the other was a retrospective cohort study (Leinig et al 2011).  Leinig, et al. demonstrated that hypoalbuminemia was a significant independent predictor of mortality [HR (95% CI): 2.3 (1.1-5.0) ] after 24 months of follow-up. Churchill, et al. described that for every g/L increase in serum albumin, there was a 2-year relative mortality risk (95% CI) of 0.94 (0.90, 0.97).

      Maintenance Hemodialysis and Peritoneal Dialysis Patients
      Both MHD and PD patients were evaluated in two prospective cohort studies (Matthew et al 2015, de Mutsert et al 2009). Mathew, et al. found that serum albumin concentration did not predict mortality and was not correlated with lean tissue index.  De Mutsert, et al demonstrated a 1g/dL decrease in serum albumin was associated with an increased mortality risk of 47% in MHD patients and 38% in PD patients (de Mutsert et al 2009).  After adjusting for systemic inflammation, or for SGA and nPNA, these mortality risk ratios were not statistically significant indicating potential confounding effects of systemic inflammation.

      In summary, one study showed that serum albumin concentration was a sensitive measure of nutritional status defined by 7-point SGA scores in MHD patients.   Seven studies indicated that serum albumin was associated with other common markers of nutritional status in MHD patients. The preponderance of evidence suggested that lower serum albumin concentration predicts mortality in both MHD and PD patients.

      Inflammatory Markers
      There were no studies examining the validity and/or reliability of utilizing inflammatory markers to measure nutritional status. Thirteen studies examined correlations between inflammatory markers and other nutrition indices, including seven studies in MHD patients, one study in PD patients, two studies in both MHD and PD patients, one study in patients with kidney transplant, and two studies in pre-dialysis patients.

      Maintenance Hemodialysis Patients:
      Among the MHD studies, all seven were cross-sectional studies (Beberashvili et al 2009, Kadiri et al 2011, Kahraman et al 2005, Jones et al 2002, Molfino et al 2013, Yelken et al 2010, Vannini et al 2009). hsCRP levels were positively associated with fat mass (Vannini et al 2009); and negatively associated with lean body mass (Vannini et al 2009), serum albumin (Jones et al 2002,  Molfino et al 2013, Yelken et al 2010,  DiSilvestro et al 1997) and serum prealbumin (Molfino et al 2013) concentrations.  hsCRP was not associated with SGA score, PNA, anthropometric indices, or BIA measurements (Vannini et al 2009). While CRP was not associated with BMI in Vannini, et al.,  there was a negative correlation in Kadiri, et al.  Kahraman, et al. found that CRP levels were highest in obese and underweight participants compared to their counterparts. Beberashvili, et al. found no relationship between proinflammatory cytokine level and BMI.

      Peritoneal Dialysis Patients 
      de Araujo Antunes, et al. conducted a cross-sectional study in PD patients.  Compared to patients with CRP level <1 mg/dL, those with CRP level  ≥1 mg/dL had higher BMI (29.4 ± 6.1 vs. 24.4 ± 4.5 kg/m ; p=0.009), % standard body weight (124.5 ± 25.4 vs. 106.8 ± 17.9 %; p=0.012), and % BF measured by SF-BIA (38.9 ± 6.3 vs. 26.2 ± 12.6 %; p<0.001).

      Maintenance Hemodialysis and  Peritoneal Dialysis Patients:
      Isoyama, et al. demonstrated that low handgrip strength, rather than low muscle mass measured with DEXA, was associated inflammatory markers including hsCRP, IL-6 and TNF-α (Isoyama et al 2014). In addition, CRP levels were negatively associated with BIA phase angle (Abad et al 2011).

      Post-Transplant Patients 
      Only one cross-sectional study was identified for kidney transplant recipients.  In this study, malnutrition inflammation score (MIS) was positively correlated with IL-6 (p=0.231; p<0.001), TNF-a (p=0.102; p<0.001), and CRP levels (p=0.094; p=0.003) (Molnar et al 2010).

      Non-dialyzed Patients 
      Both studies in pre-dialysis patients were cross-sectional in nature (Cigarran et al 2013, Wing et al 2014).  In a study by Wing, et al., hsCRP levels were higher in the highest BMI quartile, but results with other cytokines were mixed. In Stages 2-4 CKD men, CRP levels were negatively associated with testosterone distribution (Cigarran et al 2013).

      In summary, many studies found correlations between higher inflammatory markers and suboptimal nutritional status, findings varied according to comparison measure. The relationship between BMI and inflammatory marker levels was unclear, and a U-shaped relationship may exist. MIS was associated with inflammation inflammatory in kidney transplant patients. 

    • Recommendation Strength Rationale

      The evidence supporting the above statements is based on Grade I/Grade A and Consensus/expert opinion evidence.

    • Minority Opinions

      Consensus reached.