Protein energy malnutrition in CKD

Protein Energy Malnutrition
(PEM),
Protein-Energy Wasting
(PEW)
Kidney Disease Wasting
(KDW),
Kidney Disease-Related PEM
By
Mabrouk Ramadan Al-Sheikh
Prof. of nephrology and Internal Medicine
Faculty of Medicine
Tanta University

”‫ي‬‫ك‬ ‫عند‬ ‫زينتكم‬ ‫خذوا‬ ‫آدم‬ ‫بني‬ ‫ا‬‫ل‬
‫وال‬ ‫واشربوا‬ ‫وكلوا‬ ‫مسجد‬
‫يحب‬ ‫ال‬ ‫إنه‬ ‫تسرفوا‬
‫المسرفين‬“
‫العظيم‬ ‫هللا‬ ‫صدق‬
(‫األعراف‬-31)

 Eat right to feel and live right
 Do not starve your patient
 Let the food be the medicine and not let the
medicine be the food. “Hippocrates”
‫نعيش‬ ‫ال‬ ،‫لنعيش‬ ‫نأكل‬ ‫نحن‬‫لنأكل‬

Agenda
 Definition
 Prevalence
 Factors contributing to malnutrition
 Nutritional assessment
 Nutritional therapy
 Conclusion and Recommendations

Agenda
 Definition
Prevalence
Nutritional assessment

The International Society of Renal Nutrition
and Metabolism (ISRNM) expert panel
defined PEM (2012):
“state of decreased body stores of protein
and energy fuels i.e. body protein and fat
masses”
Definition

Definition
Component of PEM are
1. Clinical manifestations: unintentional poor
nutritional intake, unintentional BW loss,
depleted energy (fat tissues) stores, and loss
of somatic protein (low muscle mass).
2. Laboratory investigations: low level of
visceral protein; s. albumin, prealbumin and
transferrin and others.
3. Abnormal anthropometric measurements.

Readily utilizable criteria for the clinical diagnosis of PEM in CKD

Prevalence
Depending in part upon the method used and the
population studied, up to 40 to 70 % of patients with
end-stage renal disease are malnourished.

Potential causes of PEM in patients with non-dialysis
dependent CKD

Factors contributing to malnutrition
Malnutrition can be secondary to :
1- Poor nutritional intake:
Overzealous dietary restrictions.
Delayed gastric emptying and diarrhea.
Intercurrent illness .
Hospitalization.
Other medical cormorbidities.

Malnutrition can be secondary to :
1- Poor nutritional intake
Medication causing dyspepsia e.g. phos. binders, iron therapy .
Suppression of oral intake by PD load.
Inadequate dialysis
Decreased food intake on HD days
Monetary restriction
Depression
Altered taste sensation

2- Increased protein losses
Gastrointestinal blood loss:
“100ml blood = 14-17g protein.”
Intradialysis nitrogen loss:
“ HD : 6-8 g amino acid/ procedure”
“PD : 8-12 g protein/day”

3- Increased protein catabolism
 Intercurrent illness and hospitalizations.
 Metabolic acidosis.
 Catabolism associated with HD
 Catabolic effects of hormones “cortisol,
PTH, glucagon”
Dysfunction of GH and IGF endocrine axis.

Squeals of PEM
Malaise, fatigue, poor rehabilitation
Increase susceptibility to infection.
Impaired wound healing.
Increase hospitalization rate.
Increase morbidity and mortality rate.

Agenda
 Definition
Prevalence
 Nutritional assessment

ASSESSMENT OF NUTRITIONAL STATUS
No single gold standard measurement.
Therefore, a panel of measurements is
recommended and including:
1. Assessment of dietary nutritional intake
2. Assessment of body composition.
3. Laboratory values
4. Scoring

I-Nutritional Intake
A- Patient’s interview
• Often provides important clue to patients who
might be malnurished
• Symptoms: nausea, vomiting, anorexia, fatigue,
weight loss or gain
• Pharmacological therapy: steroid therapy, iron
therapy and phos. binder
• Co-morbidity and non uremic diseases e.g. DM,
alcoholism, GI diseases.
• Psychological issues.

Physical Examination
 Should include anthropometry
The patient's actual BW is estimated and should be
compared to the recommended “dry or peer” body
weight.
The percentile change (if any) of the "dry weight"
should also be assessed approximately every month.

B- Assessment of food intake
• Food questionnaire: the 24 h recall helps the patients to
remember food intake in the previous day and to
quantate it.
• Food record: quantitative and qualitative data on food
intake collected for an average 3 days including 2 two
week day and one week end day (3 days should include
dialysis and non-dialysis day).
• A food diary is very useful, especially if the patient
weighs the portions of food. The intake of protein, fat
and carbohydrate can then be calculated from standard
food tables.

B- Assessment of food intake:
The semi-quantitative food–frequency questionnaire
(SFFQ): is used to assess the frequency of
consumption of food items and groups during a
specific reference time period, which may or may not
be the period the patient actually bases his(her)
recalls on.

C-Protein equivalent of total nitrogen
appearance (PNA) & nPNA
Calculating the protein catabolic rate (PCR)
is a good indirect index for dietary
protein intake, expressed g/day.
KDOQI guidelines prefers the name:
protein equivalent of total nitrogen
appearance (PNA), expressed g/day.
Normalized nPNA ,expressed g/Kg/day.

C-Protein equivalent of total nitrogen
appearance (PNA) & nPNA
 Determination of nPNA: Calculated by
Formula Computer Program
 Target level =1.0-1.2 g/Kg/day.
 Best survival rate at level= 1.0-1.4 g/Kg/day.
 An increased overall mortality rate at level
<0.8 or>1.4 g/Kg/day.

Interpretation of nPNA
Observation Interpretation Consideration
nPNA exceeds DPI
or is unexpectedly
high
Only tentative
conclusions about
protein intake possible
Catabolic state:
-Inadequate energy intake
-Presence of inflammation or inflammatory
stressors (fever, infection)
-Weight loss
- Metabolic acidosis
-Bioincompatible dialysis membrane.
Inaccurate diet record
Low lean body mass
nPNA less than
DPI or is
unexpectedly low
Only tentative
conclusions about
protein intake possible
Anabolic state:
-Corticosteroid use
- Recovery from infection or illness
- Pregnancy or growth
Inaccurate diet record
Edema or excess body weight
nPNA=DPI nPNA reflects protein
intake
Conclude patient is in nitrogen balance and
nPNA reflects intake if none of the above
apply

II- Body composition
1- Body weight-based measures: BMI, weight for
height, edema-free BW, fat-free BW.
2- Skin and muscle anthropometry:
caliper, skin fold, extremity muscle mass.
3- Total body elements: total body potassium.
4- Energy-beam-based methods: total body N2,
DEXA, BIA, NIR.
5- Other method: underwater weighting.

A-BMI
The international classification of adult underweight, overweight and obesity
according to BMI
Classification BMI (kg/m2)
Underweight < 18.5
Severe thinness < 16
Moderate thinness 16-16.99
Mild thinness 17-18.49
Normal average 18.5-24.99
Overweight ≥ 25
Pre-obese 25-29.99
Obese ≥ 30
Obese class I 30-34.99
Obese class II 35-39.99
Obese class III ≥ 40

B-Anthropometry
Aim: to compare peer (ideal or average) BW to
the actual BW (special tables).
Anthropometry is practical, simple, rapid,
non-invasive, non-expensive and reproducible
technique for evaluating body fat and muscle
mass.
 It can be easily done by dietitian.

B-Anthropometry
K/DOQI guidelines :
The anthropometric measurement that are valid for
assessing nutritional status:
1. For body fat : triceps (or biceps) skin fold(TSF) .
2. For muscle mass : mid arm muscle circumference
(MAMC) &mid arm circumference (MAC).
3. For obesity : BMI
4. % of usual body weight (UBW) and % of standard
body weight (SBW).
This measures should be taken immediately post-dialysis
at right side of the body; best carried out by the same
observer

As a general rule, the percentile values/normal
limitation to the use of anthropometry is that serial
measurements are best carried out by the same
observer
adequate nutritionValues >95 %
risk of malnutritionvalues 75 % and 95 %
significant
malnutrition
values <75 %

More sophisticated measures of body composition
include :
Bioelectric impedance analysis (BIA)
Dual-energy x-ray absorptiometry (DEXA)
 A major drawback of these techniques is the
difficulty in distinguishing between fat mass and body
water.

 At present, anthropometry is the only
method that can be readily performed in most
units.
 BIA or DEXA should be reserved for selected
patients.

III-Laboratory evaluation
1. Visceral protein: negative acute phase reactants;
albumin, prealbumin, transferrin and amino
acids.
2. Lipids: chlosterol, TG and other lipids.
3. Somatic protein and nitrogen surrogates: BUN
and serum creatinine.
4. Growth factors: IGF-1 and liptin.
5. Peripheral CBC, lymphocyts.
6. Others.

I-Plasma protein measurements
 Serum albumin
 Transferrin
 Prealbumin
 Amino acids

 Serum albumin
 Transferrin
 Prealbumin
 Amino acids

Serum Albumin
Clinical practice guidelines for nutrition were
published by a working group for the NKF/DOQI
recommended that the serum albumin
concentration (obtained either predialysis or
when stable) should be measured monthly.

Serum Albumin
Impact of Low serum albumin level:
 It is strong predictor of mortality and
hospitalization; risk rises dramatically and
logarithmically as levels decline below 4.0
g/dL.
 It has been shown to predict coronary
calcification.

Serum transferrin:
Serum transferrin is not good indicator of nutritional
status; perhaps due to fluctuations in iron stores,
presence of inflammation and changes in volume
status.

Prealbumin
The plasma concentration of prealbumin (has a
shorter half-life than albumin) provides a consistent
assessment of visceral protein and can be used to
assess the response to nutritional interventions
begun for presumed malnutrition as it.
 This protein is normally excreted and metabolized by
the kidney and tends to accumulate in renal failure.

Prealbumin
Value < 30 mg/dL is indicative of malnutrition in
the patients on maintenance hemodialysis.

Amino acids
 There is a variable plasma amino acid pattern
in ESRD.
In general, the levels of the essential and
branched chain AA are decreased, while the
nonessential AA are either within the normal
range or increased.

II-Plasma cholesterol concentration
 The plasma cholesterol concentration is reduced
in malnourished patients with normal renal
function.
 Cholesterol levels are also lower in patients with
ESRDs. In this setting, there is an inverse
relationship between mortality and the
cholesterol concentration.

III-Blood urea nitrogen
Reflects the balance between urea generation and
removal
 Malnourished patients often show a gradual reduction in
BUN and become wasted.
Low levels commonly seen in dialyzed patients (well
dialyzed or inadequately dialyzed) with poor nutrition.
Low predialysis BUN levels have also been associated
with increased mortality.
It is for this reason, protein catabolic rate is monitored in
dialysis patients, since this parameter can estimate
protein intake in the stable patient.

IV-Creatinine production
Since creatinine is produced from
nonenzymatic creatine metabolism in skeletal
muscle, estimating the rate of creatinine
production has been used to assess lean body
mass in stable patients.
Estimated lean body mass was below normal
in 47 and 66 % of hemodialysis and peritoneal
dialysis patients, a presumed reflection of
inadequate nutrition.

V- C-Reactive protein
 A positive acute phase reactant protein.
 It correlates negatively with visceral protein
concentration.
 Help to uncover potential covert
inflammation especially if serum level of
albumin or prealbumin is low.

ASSESSMENT OF NUTRITIONAL STATUS
No gold standard measurement.
Therefore, a panel of measurements is
recommended and including:
1. Assessment of dietary nutritional intake
2. Assessment of body composition.
3. Laboratory values
4. Scoring

Subjective global assessment (SGA)
• Conventional SGA is a simple method depends
on the experience of clinician to make an
overall evaluation of nutritional status.
• Advantages: includes objective data and
several manifestations of poor nutritional
status.
• Limitation: heavy reliance on the clinical
judgment and the inability to tailor a specific
nutritional therapy.

This is a clinical method for evaluation of
nutritional status; including:-
A- History and symptoms:
1- % of weight loss in the last 6 months
2- Dietary nutrient intake
3- Presence of anorexia, nausea, vomiting, diarrhea
or abdominal pain
4- Functional capacity
5- Metabolic demands in the view of activity

B-Physical parameters focus on:
• Assessment of subcutanous fat.
• Assessment of muscle wasting in the temporal
area, deltoid and quadriceps.
• Presence of sacral or ankle odema.
• Presence of ascites.

The SAG has good reproducibilty and correlates
well with outcome in ESRD.

Indices of malnutrition in HD patients
1. S. albumin concentration < 4.0 gm/dl.
2. Low s.prealbumin concentration (<30 mg/ dl)
3. Low b. urea & s. creatinine level in patients
with residual renal function.
4. PCR < 0.8gm/Kg/day.
5. Chol. concentration<150mg/dl(3.9mmol/L).
6. Transferrin <150 mg/dl.

Indices of malnutrition in HD patients
7. IGF-1 concentration < 300 µg/L.
8. Low predialysis serum K (and possibly
phosphororus) concentration.
9. Marked reduction in anthropometric
measurement
10. Continuous decline in estimated dry weight.
11. BW < 80% of ideal weight.

Agenda
• Definition
• Factors contributing to malnutrition
• Disorders of nutrient metabolism in CKD
• Nutritional assessment
• Nutritional therapy
• Conclusion and Recommendations

Nutritional therapy
Why malnutrition should be corrected?
 Many studies documented that poor
nutritional status increases the morbidity and
mortality CKD patients.
 Specifically; low s. creatinine ,albumin
concentration and % of ideal dry BW at time
of initiation of maintenance dialysis are
associated with increased risk of morbidity
and mortality during sub sequent years of HD.

Why malnutrition should be corrected?
PEM is one of the strongest predictors of
mortality and morbidity and is the third of the
killing triad in CKD and HD patients
1.CV accidents
2.Infection
3.PEM
Nutritional therapy

Interventions to prevent and/or treat malnutrition
in advanced kidney failure
CKD patients:
1- Close supervision and nutritional counseling (especially for patients on protein-
restricted diets).
2- Initiation of dialysis or kidney transplant in advanced CKD patients with
apparent uremic malnutrition despite vigorous attempts to rectify it.
Maintenance dialysis patients:
1- Appropriate amount of dietary protein (> 1.2 g/kg/day) and calorie (> 35
kcal/kg/day) intake.
2- Optimal dose of dialysis (urea reduction ratio > 70%).
Use of biocompatible hemodialysis membranes.
3-Nutritional support in chronic dialysis patients who are unable to meet their
dietary needs:
a-Oral supplements.
b-Tube feeds (if medically appropriate).
c-Intradialytic parenteral nutritional supplements for HD patients.
d-Amino acid dialysate for peritoneal dialysis patients.
e-TPN

Nutritional therapy
Strategies for correction of malnutrition
I. Dietary counseling, support and optimization.
II. Adequate dialysis.
III. Nutritional support in chronic HD patient who
are unable to meet their dietary needs:
1- Oral supplementation.
2- Tube feeding(if medically appropriate).
3- IDPN supplements for HD patients.
4- AA dialysate for PD patients.
5-Continuos total parenteral nutrition(TPN)

Nutritional therapy
Other interventions
1. Correction of anemia, metabolic acidosis and
SHPT.
2. Anabolic agents :insulin, growth factor, or
androgenic anabolic steroid.
3. Exercise.
4. Treatment of inflammation :statin, vit E.
5. Social work.
6. Pharmacy support.
7. Transplantation.

Nutritional therapy
Dietary requirement
The recommended average level of nutritional
intake are listed in the following table.
These recommendations are consistent with
NKF ,KDOQI and EBP guidelines for nutrition
for CKD patient.

Recommended intakes of protein, energy, and minerals
in kidney failure
Protein Energy Phosphorus Sodium
Chronic kidney disease
-Stages 1-3 (GFR > 30
ml/min)
-Stages 4-5 (GFR < 30
ml/min)
No restriction
0.60-0.75
g/kg/day
No restriction
35 kcal/kg/day
600-800 mg/day
600-800 mg/day
< 2 g/day
< 2 g/day
End-stage renal disease
-Hemodialysis
- Peritoneal dialysis
> 1.2 g/kg/day
> 1.3 g/kg/day
35 kcal/kg/day
35 kcal/kg/day
600-800 mg/day
600-800 mg/day
< 2 g/day
< 2 g/day
Acute renal failure
-No dialysis
- Dialysis
1-1.2 g/kg
IBW/day
1-1.2 g/kg
IBW/day
35 kcal/kg/day
35 kcal/kg/day
600-800 mg/day
600-800 mg/day
< 2 g/day
< 2 g/day

74
Recommended vitamin intake for patients
receiving maintenance hemodialysis
Thiamine (B1) 1.1–1.2 mg/day
Riboflavin (B2) 1.1–1.3 mg/day
Niacin 14–16 mg/day
Pantothenic Acid 5 mg/day
Vitamin B6 10 mg/day
Vitamin B12 2.4 mg/day
Biotin 30 mcg/day
Vitamin C 75–90 mg/day
Folic acid 1 mg/day
Zinc 15 mg/day

Nutritional therapy
Needs for individualization
Adherence to the renal diet is difficult & stressful.
Prescribed diet should be individualized to help every
patient in the terms of: cost, palatability,
comorbidities and cultural eating habits.
Too many restriction should be avoided as they may
lead to poor intake.
Reinforcement by all members of the family and
medical stuff.
Compliance should be assessed on regular basis even
monthly .

Strategies to enhance oral intake

Adequacy of dialysis
Early referral to dialysis is very crucial.
 Optimal dose of dialysis(URR>70%).
 Use of biocompatible HD membrane.
 Keep KT/V =1-1.2
 An important consensus:
Adequate dialysis coupled with good
nutrition is the main pillar for best quality of life.
Adequate dialysis corrects uremia & anorexia
which enhance nutrition.

Peer rather than actual BW
Protein and caloric recommendation should
be based on the peer BW for healthy subjects
of the same age, sex, height and body frame
size as the patients.

Recommendation
• Understanding and application of the nutritional
principles.
• Periodic assessment of nutritional status (once/
month) should be part of the routine care of CKD and
dialysis patients to permit early recognition.
• Providing and institution of appropriate therapy for
the best improvement of nutrition status .
• Renal dietitian should be a member of the medical
personals.

Take home message
• PEM is underappreciated, although it largely
preventable and completely curable.

88
Recommended vitamin intake for patients
receiving maintenance hemodialysis
Thiamine (B1) 1.1–1.2 mg/day
Riboflavin (B2) 1.1–1.3 mg/day
Niacin 14–16 mg/day
Pantothenic Acid 5 mg/day
Vitamin B6 10 mg/day
Vitamin B12 2.4 mg/day
Biotin 30 mcg/day
Vitamin C 75–90 mg/day
Folic acid 1 mg/day
Zinc 15 mg/day

Recommended daily dietary intake for adult
patients on maintenance hemodialysis

Vitamins
EBPG nutrition, NDT 2007

A conceptual model for etiology of PEW in
CKD and direct clinical implications.

Response to reduced dietary protein and
energy intake.

Response to reduced dietary protein and
energy intake.
• (A) Normal response. Reduced dietary protein and energy drive an
increase in hunger and
• a fall in REE, loss of protein preferentially from the visceral organs,
and increased insulin sensitivity of muscle.The liver and kidney
provide glucose, and serum albumin is maintained at a normal level.
• (B) Response with PEW. During PEW, the adaptations to increase
hunger and lower REE are blunted in part by an increased half-life of
leptin and ghrelin and in part by inflammation and dialysis. The loss
of protein occurs preferentially from muscle because of the effects of
metabolic acidosis, glucocorticoids, and inflammation, leading to
increased insulin resistance. Dialysis results in the loss of amino
acids, stimulating muscle protein breakdown. Under the influence of
inflammation and metabolic acidosis, the liver makes glutamine for
deamination in the kidney, increases acute-phase reactants, and
reduces serum albumin. The kidney increases glucose production
from glutamine under the influence of metabolic acidosis.

Potential causes of frailty and protein-energy wasting
in elderly patients with end stage kidney disease.

Clinical consequences of frailty and protein-energy
wasting in elderly patients with end stage kidney
disease.

Potential preventive and therapeutic strategies
for frailty and PEW in elderly ESRD patients

Readily utilizable criteria for the clinical diagnosis of protein
energy wasting in chronic kidney disease criteria

Selected nutritional parameters for varying
levels of kidney disease

Potential causes of protein-energy wasting in patients
with non-dialysis dependent chronic kidney disease

Methods of evaluation for diagnosis of PEM in
patients with non-dialysis- dependent CKD

Schematic representation of the development of
protein-energy wasting with advancing stages of CKD

Selected nutritional parameters for varying
levels of kidney disease (K/DOQI guidelines)
Nutritional
Parameters
Stages 1-4 CKD Stage 5
Hemodialysis
Calories (kcal/kg/d) 30 – 35 35 - 60
Protein (g/kg/d) 0.6 – 0.75 1.2
Fat (% total kcal) For patients at risk for CVD, < 10%
saturated fat, 250-300 mg cholesterol/d
Sodium (g/d) < 2 2
Potassium (g/d) Match to laboratory
values
2 - 3
Calcium (g/d) 1.2 2 from diet and
medicines
Phosphorus (mg/d) Match to laboratory
values
800 – 1000
Fluid (ml/d) Unrestricted with
normal urine output
1000 + urine

Protein energy malnutrition in CKD

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