Assessment of MICS

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Classically, three major lines of inquiry, i.e. dietary intake, biochemical measures, and body composition, are used to assess the protein-energy nutritional status; a fourth category of nutritional assessment, composite indices that include a com-

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Fig. 2. Mean levels of biochemical measures of nutritional status as a function of glomerular filtration rate (GFR) in MDRD Study. The estimated mean levels with 95% confidence limits of biochemical nutritional markers are shown as a function of GFR (males solid line, females dashed line) controlling for age, race, and use of protein and energy restricted diets. In men, the slope of the relationship was greater at GFR = 12 than GFR = 55 ml/min/1.73 m2 for serum total cholesterol (p = 0.014). a Males, N = 1065 (p = 0.004); females, N = 698 (p < 0.001). b Males, N = 1065 (p < 0.001); females, N = 698 (p < 0.001). c Males, N = 1063 (p = 0.052); females, N = 694 (p = 0.63). d Males, N = 1017 (p < 0.001); females,N = 664 (p < 0.001). (Modified from [54,55])

b a d c bination of assessment measures within these categories, are also utilised, especially the Subjective Global Assessment of Nutrition (SGA) [68,69] and Malnutrition-Inflammation Score (MIS) [28, 70]. The four categories of nutritional assessment tools are described in Table 3 and have been reviewed in detail elsewhere [22, 71]. As indicated in Table 3, many of these nutritional assessment tools are also designed to detect a combination of protein-energy malnutrition and inflammation and to grade their severity. Hence, the overlap between malnutrition and inflammation also exists at the diagnostic level, in addition to their overlapping aetiologies.

No uniform approach has been agreed upon for rating the overall severity of protein-energy malnutrition. Among all four categories, dietary assessment is probably the most nutrition-specific entity. Another, rather nutrition-focused measure is the normalised protein equivalent of total nitrogen appearance (nPNA), also known as protein catabolic rate (nPCR); a low nPNA is associated with increased hospitalisation and mortality in haemodialysis patients even when the dose of

Table 2. Conditions related to protein-energy malnutrition as a cause of wasting syndrome in CKD patients

A. Inadequate nutrient intake

1. Anorexiaa a. Due to uraemic toxicity b. Due to impaired gastric emptying c. Due to inflammation with or without comorbid conditions3

d. Due to emotional and/or psychological disorders

2. Dietary restrictions a. Prescribed restrictions: low-potassium, low-phosphate regimens b. Social constraints: poverty, inadequate dietary support c. Physical incapacity: inability to acquire or prepare food or to eat

B. Nutrient losses during dialysis

1. Loss through haemodialysis membrane into haemodialysate

2. Adherence to haemodialysis membrane or tubing

3. Loss into peritoneal dialysate

C. Hypercatabolism due to comorbid illnesses

1. Cardiovascular diseasesa

2. Diabetic complications

3. Infection and/or sepsisa

4. Other comorbid conditionsa

D. Hypercatabolism associated with dialysis treatment

1. Negative protein balance

2. Negative energy balance

E. Endocrine disorders of uraemia

1. Resistance to insulin

2. Resistance to growth hormone and/or IGF-1

3. Increased serum level of or sensitivity to glucagons

4. Hyperparathyroidism

5. Other endocrine disorders

F. Acidaemia with metabolic acidosis

G. Concurrent nutrient loss with frequent blood losses aThese factors may also be associated with inflammation; IGF-1, insulin-like growth factor 1

dialysis is standard or high (Kt/VSp > 1.20) [20]. Although, as discussed above, it has been argued that appetite can be suppressed by inflammation and particularly by two pro-inflammatory cytokines, IL-6 and TNF-a [41, 72], the reduced nutritional state is still expected to induce malnutrition and its consequences regardless of the cause of anorexia.

Some more frequently studied indicators of malnutrition in dialysis patients that are associated with clinical outcome include decreased dietary protein and energy intake [20, 60]; reduced weight-for-height [57], body mass index (BMI) [73-75] and total body fat percentage [76, 77]; decreased total body nitrogen [78, 79] and total body potassium [80]; reduced mid-arm muscle mass and skinfold thicknesses [81]; low serum concentrations of albumin [82], prealbumin (transthyretin) [83, 84], transferrin (TIBC) [68, 85], cholesterol [86,87], and creatinine [88]; and a more abnormal score by such nutritional assessment tools as the SGA [89, 90] and MIS [28]. Although the foregoing measures of nutritional status have practical value, it should be recognised that each of these methods has its limitations. For example, serum albumin, transferrin, and preal-bumin are negative acute-phase reactants and may reflect inflammation [46, 68, 91]. The SGA may also be a marker of the degree of sickness and comorbidity in maintenance dialysis patients [68]. During acute catabolic states and hyperca-tabolism, the urea nitrogen appearance may transiently increase independently of food intake [92]. More elaborate nutritional measures that have

Table 3. Assessment tools for the evaluation of protein-energy malnutrition in CKD patients. (Data from [22,71])

A. Nutritional intake

1. Direct: diet recalls and diaries, food frequency questionnaires

2. Indirect: based on urea nitrogen appearance: nPNA (nPCR)

B. Body composition

1. Weight based measures: BMI, weight-for-height, oedema-free/fat-free weight

2. Skin and muscle anthropometry via caliper: skinfolds, extremity muscle mass

3. Total body elements: total body potassium

4. Energy-beam based methods: DEXA, BIA, NIR

5. Other energy-beam related methods: total body nitrogen

6. Other methods: underwater weighing

C. Laboratory values

1.Visceral proteins (negative acute-phase reactants): albumin, prealbumin, transferrin3

2. Lipids: cholesterol, triglycerides, other lipids, and lipoproteins8

3. Somatic proteins and nitrogen surrogates: creatinine, SUN

4. Growth factors: IGF-1, leptin

5. Peripheral blood cell count: lymphocyte count

D. Scoring systems

1. Conventional SGA and its modifications (e.g. DMS,MIS, and CANUSA)a

2. Other scores: HD-PNI, others (e.g. Wolfson, Merkus, Merckman)a aThese tools may also detect inflammation nPNA, Normalised protein nitrogen appearance; nPCR, normalised protein catabolic rate; BMI, body mass index; DEXA, dual energy X-ray absorptiometry; BIA, bioelectrical impedance analysis; NIR, near infra-red interactance; SGA, subjective global assessment of nutritional status; DMS, dialysis malnutrition score; MIS, malnutrition inflammation score; CANUSA, Canada-USA study based modification of the SGA; HD-PNI, haemodialysis prognostic nutritional index; SUN, serum urea nitrogen; IGF-1, insuline-like growth factor 1

been used in dialysis and CKD patients include dual energy X-ray absorptiometry (DEXA) [93, 94], total body nitrogen or potassium measurements [79, 80, 95], underwater weighing [96], bioelectrical impedance analysis (BIA) [94], and near infra-red interactance (NIR) [76,97].

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