Assessment of nutritional status in patients on hemodialysis

INTRODUCTION — Patients on dialysis are commonly depleted of protein and energy stores [1-5]. The degree to which protein and energy depletion is the result of deficient nutrition or, alternatively, protein and energy wasting is unclear. In 2009, the International Society of Renal Nutrition and Metabolism (ISRNM) recommended the terminology protein-energy wasting (PEW) syndrome to describe the loss of body protein mass and fuel reserves in patients with end-stage kidney disease (ESKD) [6].

The assessment of nutritional status is a routine part of the care of patients on maintenance dialysis in order to allow early recognition and treatment of PEW syndrome. Markers of PEW are among the strongest predictors of morbidity and mortality in patients with ESKD [3,7].

This topic reviews our approach to the assessment of nutritional status among hemodialysis patients. The pathogenesis and treatment of PEW among hemodialysis patients are discussed elsewhere. (See "Pathogenesis and treatment of malnutrition in patients on maintenance hemodialysis".)

The assessment of nutritional status and the prevention and treatment of malnutrition among peritoneal dialysis patients are discussed elsewhere. (See "Nutritional status and protein intake in patients on peritoneal dialysis".)

OUR APPROACH TO THE CLINICAL ASSESSMENT OF NUTRITIONAL STATUS — We perform monthly nutritional assessments of all hemodialysis patients. Our approach includes a dietary assessment, physical examination, and laboratory examination.

Our approach is detailed here.

Dietary assessment — We question patients monthly about loss of appetite, loss of weight, or development of gastrointestinal symptoms such as nausea or vomiting. We inquire as to psychosocial issues such as access and affordability of food, ability to prepare meals, and the role of family members in food preparation.

We do not routinely conduct three-day dietary recalls to assess adequacy of nutrient intake as is recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines [8]. Dietary recall is burdensome to staff and patients and relies on patient memory and compliance with recording. Furthermore, there is no randomized, controlled trial evidence to support this intensive strategy. We believe the protein nitrogen appearance (PNA), which is calculated using pre- and postdialysis blood urea nitrogen (BUN), is a better indicator of protein intake and subject to less measurement error then dietary diaries. (See 'Urea nitrogen and protein nitrogen appearance' below.)

An exception may be made among patients with difficult-to-control hyperkalemia or hyperphosphatemia; in such patients, dietary recall may be helpful.

We are vigilant regarding signs or symptoms of depression since clinical depression often results in a disinterest and decrease in caloric intake. (See "Psychiatric illness in adults receiving maintenance dialysis", section on 'Major depression'.)

The clinician should be aware of the presence of concomitant problems that can affect nutrition, such as alcoholism, diabetes mellitus gastrointestinal disease, and dental disorders [9].

Physical assessment — We measure postdialysis edema-free weight every month. We use the weight to calculate the body mass index (BMI) and to monitor for weight loss. Given the dependency of the weight on the height, BMI is a better measurement of body mass than body weight alone [10]. In some patients who cannot achieve postdialysis euvolemia for a variety of reasons, we monitor the trend of their weight with simultaneous assessment of interdialytic weight gain and volume.

We do not use an adjusted body weight (ie, express actual weight as a percentage of standard body weight determined from the National Health and Nutrition Examination Survey [NHANES] II), which has been suggested to better define nutritional needs [11]. The impact of adjusted body weight on clinical outcomes has not been adequately studied.

As in the general population, a low BMI or unintentional weight loss are consistent predictors of poor outcome and high death risk in maintenance dialysis patients [12,13].

The BMI threshold that indicates protein-energy wasting (PEW) is not known with certainty. The International Society of Renal Nutrition and Metabolism (ISRNM) panel recommends that a BMI less than 23 kg/m² is a marker of PEW in the dialysis population. However, the accuracy of this threshold is influenced by race and ethnicity. In particular, this BMI may not indicate a pathologic state among patients of East Asian descent [14,15].

Unintentional weight loss or reduction in BMI of any degree suggests the presence of PEW in dialysis patients. The ISRNM panel recommends that a loss of 5 percent of nonedematous weight within three months or an unintentional loss of 10 percent of nonedematous weight over six months should be considered an indicator of PEW independently of weight-for-height measures. A decline in BMI over time may be associated with increased mortality [16].

We do not measure skinfold thickness or mid-arm circumference (MAC) in routine clinical practice.

Laboratory assessment — We measure the serum albumin and pre- and postdialysis BUN monthly. We use the BUN to calculate the PNA. (See 'Serum albumin' below and 'Urea nitrogen and protein nitrogen appearance' below.)

We do not use any other laboratory measurements for routine nutritional assessment. Although multiple other measures are available, the practical utility of these tests in routine clinical practice is unclear. (See 'Other methods' below.)

Serum albumin — A serum albumin <3.8 g/dL is a suggested diagnostic criterion for PEW syndrome (table 1) [6].

However, this threshold has not been validated as a measure of either protein or energy wasting. It is possible that a more stringent threshold would be a better indicator of wasting, although this requires study.

The serum albumin levels is widely used to assess the nutritional status of individuals with and without chronic kidney disease (CKD). The serum albumin levels generally correlate with changes in dietary protein intake [17].

A low serum albumin is one of the strongest predictors of outcomes in CKD and dialysis patients [10,18,19]. However, serum albumin levels may also fall due to non-nutritional factors including inflammation, acute or chronic stress, overhydration, urinary or peritoneal losses, and acidemia [20-22]. It may not be possible to delineate whether the nutritional component or other non-nutritional factors that are associated with hypoalbuminemia are responsible for the higher mortality.

It is important to be aware of the method used to measure albumin since different methods yield different results, specifically among end-stage kidney disease (ESKD) patients.

The gold-standard method for the measurement of serum albumin is nephelometry. However, nephelometry is not commonly used in clinical practice, since it is a costly and tedious procedure. Serum albumin is more commonly measured by either bromocresol green method or bromocresol purple method. Among ESKD patients, albumin estimation by bromocresol green method more closely estimates values obtained by nephelometry, whereas the bromocresol purple method underestimates the albumin concentration [23-25]. This is different from patients without ESKD in whom the bromocresol purple method is more accurate [24,26].

Urea nitrogen and protein nitrogen appearance — Malnourished patients often show a gradual reduction in BUN. Low predialysis BUN levels have been associated with increased mortality [27].

However, in addition to protein intake, BUN levels are affected by residual kidney function and adequacy of dialysis. The PNA calculated from the BUN better estimates protein intake in the stable patients. (See "Protein intake in patients on maintenance hemodialysis".)

The PNA is calculated from the post- and predialysis BUN concentrations of two consecutive hemodialysis sessions. The rate of increase in serum urea nitrogen between two consecutive hemodialysis sessions reflects dietary nitrogen intake, provided that the individual is not in substantially negative or positive nitrogen balance (or, in other words, neither catabolic nor anabolic) and providing the patient does not have significant residual kidney function. Among patients with residual kidney function, total urea lost in the urine must also be measured from urine collected during the interdialytic period. (See "Protein intake in patients on maintenance hemodialysis", section on 'Calculation'.)

In well-dialyzed patients, a PNA <1.2 g/kg/day suggests poor nutrient intake or signals the onset of an intercurrent illness. PNA may overestimate daily protein intake when the protein intake is less than 1 g/kg/day (possibly due to endogenous protein catabolism) [28-30].

National guidelines (based on opinion) recommend maintaining a PNA >1.2 g/kg/day [31,32].

DIAGNOSIS OF PROTEIN-ENERGY WASTING — We believe that the diagnosis of protein-energy wasting (PEW) is suggested by any progressive decrease in body mass index (BMI), albumin, and protein nitrogen appearance (PNA) rather than by a defined threshold in any parameter. Specific indications for treatment and our approach to the treatment of PEW are discussed elsewhere. (See "Pathogenesis and treatment of malnutrition in patients on maintenance hemodialysis".)

Several criteria have been proposed for the diagnosis of PEW [6]. However, we do not recommend using these criteria for routine clinical practice, as they have not been validated for the diagnosis of PEW, and using criteria has not been shown to improve clinical outcomes. These proposed criteria are discussed below:

●International Society of Renal Nutrition and Metabolism – The International Society of Renal Nutrition and Metabolism (ISRNM) expert panel recommends that four categories be recognized for the diagnosis of PEW, including biochemical criteria; low body weight, reduced total body fat, or weight loss; a decrease in muscle mass; and low protein or energy intakes (table 2) [6]. At least three out of the four listed categories (and at least one test in each of the selected category) must be satisfied for the diagnosis of PEW. Optimally, each criterion should be documented on at least three occasions, preferably two to four weeks apart.

●Subjective global assessment – Subjective global assessment (SGA) is based on subjective and objective aspects of the patient’s medical history and physical examination and can be performed rapidly without need for much training [33]. In brief, four items are scored. These items include a change in dry body weight, a change in dietary intake and gastrointestinal symptoms, a decrease of subcutaneous fat, and muscle atrophy.

Patients are subjectively scored from 1 (severely malnourished) to 7 (well nourished). A fair intra- and inter-rater reliability and validity of SGA have been demonstrated in end-stage kidney disease (ESKD) population [34-36], and it has shown to be predictive of mortality [36-38].

●French protein-energy wasting score – The French PEW score grades one selected item in each of the four categories of the wasting syndrome (table 1). The selected items include serum albumin (for serum chemistry), body mass index (BMI; for body mass), predialysis serum creatinine normalized by body surface area (for muscle mass), and normalized protein nitrogen appearance (PNA; for dietary intake) [39].

In a three-year dialysis follow-up cohort including 1443 patients, there was a reduction in survival for each unit decrement in the score grade. In addition, the six-month variation of this PEW score strongly predicted patients' survival [39].

●Mini Nutritional Assessment – The Mini Nutritional Assessment short form (MNA-SF) score consists of six short sections that can easily and quickly be completed in clinic. Categories include food intake, weight loss, mobility, recent psychological stress or acute disease, neuropsychological problems, and BMI (www.mna-elderly.com/sites/default/files/2021-10/mna-mini-english.pdf). In a study of 216 patients on dialysis, the MNA-SF identified inadequately nourished (ie, either at risk for malnutrition or malnourished) patients with a sensitivity, specificity, and negative predictive value of 0.95, 0.63, and 0.91, respectively. The MNA-SF score also was associated with mortality [40].

OTHER METHODS — Multiple other measures have been used for nutritional assessment. The practical utility of these tests in routine clinical practice is unclear. Commonly used tests are discussed here:

●Prealbumin – The plasma concentration of prealbumin (transthyretin) varies with the state of nutrition in patients with normal kidney function [41]. However a single value may not be an accurate predictor of nutrition among end-stage kidney disease (ESKD) patients, since prealbumin is normally excreted and metabolized by the kidney and accumulates in kidney failure [42].

Serial measurements can be monitored once a baseline level has been established for the individual patient. Prealbumin concentrations change rapidly in response to alterations in nutritional status and can be used to assess the response to nutritional interventions.

In addition to nutritional status, low prealbumin levels may also reflect an acute intercurrent illness. One study also found that decreased prealbumin levels correlated independently with increased mortality and hospitalization due to infection [43].

●Serum transferrin – Among hemodialysis patients, transferrin correlates with nutritional status independent of patient age, dialysis vintage, iron status, or other hemoglobin-related factors [44]. Transferrin also correlates with clinical outcome [45].

●Serum cholesterol – The plasma cholesterol concentration is reduced in malnourished hemodialysis patients. In this setting, there is an inverse relationship between mortality and the cholesterol concentration [7,46]. Cholesterol may be influenced by the same comorbid conditions, such as inflammation, that affect other nutritional markers (eg, serum albumin) [42].

●Serum creatinine – As creatinine is produced by muscle, serum creatinine is an indicator of muscle mass in hemodialysis patients. However, in addition to muscle mass, meat intake, residual kidney function, and nonrenal excretion through the gastrointestinal tract affect serum creatinine levels. Furthermore, the threshold level of serum creatinine that indicates malnutrition has not been defined.

●Waist or hip circumference or waist-to-hip ratio (WHR) – These indicators of abdominal obesity reflect the risk associated with excessive visceral fat, which is the most relevant fat compartment for cardiovascular risk [47-49]. Waist circumference measurement is particularly useful in patients who are categorized as normal or overweight, but not obese, on the body mass index (BMI) scale. At BMIs greater than or equal to 35 (ie, obese individuals), waist circumference adds little predictive power of disease risk to the BMI.

Waist circumference (WHR) is measured over the unclothed abdomen just above the iliac crest, and hip circumference is measured at the level of the widest diameter around the buttocks [50]. A strong association among waist circumference, WHR, and cardiovascular risk factors has been demonstrated in chronic kidney disease (CKD) and dialysis patients [51]. In a study cohort of 537 dialysis patients, after adjustment of BMI, every 10 cm increase in waist circumference was associated with 49 percent increased risk of all-cause mortality and 55 percent increased risk of cardiovascular mortality [52]. Every increase in WHR by 0.1 was associated with 25 percent increased risk of mortality [52].

●Body composition – Assessment of body compartments such as fat mass, muscle mass, and bone mass can contribute to better understanding of the role of nutritional variables in clinical outcomes in dialysis patients. The techniques that are used to assess body composition include anthropometry, creatinine kinetics, bioimpedance analysis (BIA), dual-energy x-ray absorptiometry (DXA), computed tomography (CT), or magnetic resonance imaging (MRI).

•Anthropometry – Anthropometry is simple and quick to carry out but is not as accurate as more sophisticated techniques. Commonly used measurements include mid-arm muscle circumference, which estimates muscle mass at the mid-arm level, and skinfold thickness, which may be used to estimate total body fat percentage [53].

Anthropometry is most useful if serial measurements are carried out by the same observer. Inability to do this limits its utility. More sophisticated measures of body composition described below have largely superseded anthropometry.

•Bioimpedance analysis – BIA is relatively inexpensive, easy to use, noninvasive, portable, and requires little operator training to be performed [54,55]. BIA measures impedance or resistance to the flow of an electrical current within the body, which is used to determine total body water and can distinguish muscle mass from fat.

However, as BIA uses estimation of water content to calculate muscle mass, volume status could influence the results.

•Dual-energy x-ray absorptiometry – DXA is a reliable and noninvasive method to assess the three main components of body composition (fat mass, fat-free mass, and bone mineral mass and density) [56]. DXA has been validated in CKD and dialysis patients [57-59]. Similar to BIA, estimation of muscle mass may be affected by hydration status. Additional limitations are the use of irradiation, cost, need for dedicated space for the equipment, and travel to the facility.

•Creatinine kinetics – Creatinine kinetics may be used as an indicator of muscle mass, although interpretation may be limited by residual kidney function [5]. Creatinine kinetics are laborious and not widely used.

●Imaging techniques – Imaging techniques such as whole-body CT or MRI scans can be used to quantitate whole body muscle mass but are expensive to perform [60]. Thigh images have been used to estimate thigh muscle area/mass as an indicator of whole body muscle mass [61]. A single MRI scan at L4-L5 level may be used to estimate visceral fat area and lean body mass [61,62].

●Muscle strength – Muscle strength may be a stronger predictor of mortality than absolute muscle mass [63]. However, performance on muscle strength tests may be affected by age, cognition, medications (such as sedatives), smoking, alcohol consumption, etc [64].

SUMMARY AND RECOMMENDATIONS

●Protein-energy wasting syndrome – Dialysis patients are commonly depleted of protein and energy stores as a result of either deficient nutrition or protein and energy wasting. The term protein-energy wasting (PEW) syndrome describes the loss of body protein mass and fuel reserves in patients with end-stage kidney disease (ESKD). (See 'Introduction' above.)

●Clinical assessment of nutritional status – We perform monthly nutritional assessments of all hemodialysis patients. Our approach includes a dietary assessment, physical examination, and laboratory examination. We do not routinely conduct three-day dietary recalls to assess adequacy of nutrient intake. (See 'Dietary assessment' above.)

•Physical assessment – We monitor postdialysis edema-free weight every month for evidence of weight loss and to calculate the body mass index (BMI). A low BMI or unintentional weight loss suggests PEW and is a predictor of poor outcome and high death risk in maintenance dialysis patients. (See 'Physical assessment' above.)

•Laboratory assessment – We measure the serum albumin and pre- and postdialysis blood urea nitrogen (BUN) monthly. We use the BUN to calculate the protein nitrogen appearance (PNA). We do not use any other laboratory measurements for routine nutritional assessment. (See 'Laboratory assessment' above.)

●Diagnosis of protein-energy wasting – The diagnosis of PEW is suggested by any progressive decrease in BMI, albumin, and PNA. Although several criteria have been proposed for the diagnosis of PEW, we do not use these criteria for routine clinical practice, since their use has not been shown to improve clinical outcomes in dialysis patients. Furthermore, while these criteria have been empirically developed, the validity of these criteria for protein or energy wasting needs to be established. (See 'Diagnosis of protein-energy wasting' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Marsha Wolfson, MD, FACP, who contributed to earlier versions of this topic review.