in PD Patients - APCN 2010

Peritoneal Dialysis and Nutrition
Seung Hyeok Han, MD, PhD
Dae-Suk Han, MD, PhD
Department of Internal Medicine,
Yonsei University College of Medicine, Seoul, Korea

Nutritional Problems in
Dialysis Patients
• Protein-energy wasting (PEW)
• Overweight / obesity
• Metabolic syndrome

Metabolic Syndrome (MeS) in PD Patients
• Higher prevalence in PD (50%) than in HD
(20%) and predialysis (30%) patients
• Asian PD patients
- 53.3% in Hong Kong
- 55% in Taiwan
- 47.2% in Korea
• MeS is an independent risk factor of mortality in
non-diabetic PD patients.
• Not clear whether the use of a diagnosis of MeS
would be better than using each risk factors
separately as a predictor of CVD in PD patients.

MeS Predicts Mortality in Non-Diabetic
PD Patients
Park et al, NDT 2010

PD and Obesity
• Patients commonly gain weight post-PD,
particularly in the first year of PD.
• Some patients may have excessive weight gain
(more than 10 kg).
• Mainly due to increase in fat mass including
the abdominal fat.
• No significant relation between peritoneal
glucose absorption and changes in fat mass.
• By BMI, 50.9% of prevalent PD patients were
overweight (BMI > 25 kg/m 2 )

Consequences of Obesity
• Higher risk of peritonitis and technique failure
• Risk of further weight gain
• More rapid loss of RRF
• Risk of inadequate dialysis
• Impact on outcomes

Is It Good to be Fat in
Dialysis Patients ?
• Numerous observational studies suggest that
higher BMI is associated with better outcome in HD.
• However, association of BMI with outcomes is
controversial in PD patients.
• Better survival - Johnson et al, PDI 2000
Snyder et al, KI 2003
• Higher risk of death - McDonald et al, JASN 2003
Stack et al, KI 2004

Should Dialysis Patients be
Encouraged to Become Obese?

Association Between BMI and Mortality is
Similar in HD and General Population at High
Age and Equal Duration of F/U

Both Body Size and Body Composition
Influence Survival of Incident PD Patients
Body composition group HR for All-Cause Death HR for CV Death
Normal BMI (18.5-24.9 kg/m 2 )
and Ucr > 0.64 g/day
Reference
Reference
Normal BMI (18.5-24.9 kg/m 2 )
and Ucr ≤ 0.64 g/day
High BMI (≥ 25 kg/m 2 )
and Ucr > 0.64 g/day
High BMI (≥ 25 kg/m 2 )
and Ucr ≤ 0.64 g/day
1.20 (1.09-1.31) 1.22 (1.08-1.38)
0.90 (0.83-0.97) 0.88 (0.79-0.97)
1.29 (1.17-1.42) 1.21 (1.06-1.39)
Ramkumar et al, PDI 2005

Obese Sarcopenia in ESRD Patients is
Assoicated with Inflammation and
Increased Mortality
• PEW was present in 60% of patients with BMI < 20
kg/m 2 , 39% with BMI 20-25 kg/m 2 .
• Overweight patients (BMI > 25 kg/m 2 ) also had high
prevalence of PEW (16%).
• Obese sarcopenia group had highest levels of IL-6,
CRP, and fat body mass index, and FBMI/LBMI
ratio.
• For each BMI group, the presence of PEW was
associated with increased mortality.
Honda et al, Am J Clin Nutr 2007

The Muscle Matters, Not the Fat

Obesity and Protein-Energy Wasting in PD
Patients is a Two-Dimensional Problem
• Nutritional problems in PD patients cannot be
merely classified on the basis of BMI.
• High body mass in the presence of low muscle
mass and PEW underlies a high death risk (obese
sarcopenia).
• Prognostic value of nutritional status in PD patients
should be based on BMI and muscle mass and/or
protein-energy balance.

Malnutrition
• Refers to abnormalities induced by low nutrient
intake or intake that is inadequate for the nutritional
needs of the individual
• Results in altered metabolism, impaired function,
and reduced body mass
• Can be corrected by increasing the diet

Protein-Energy Wasting (PEW)
• State of decreased body store of protein and
energy fuels (body protein and fat mass)
• In kidney disease, there are conditions resulting in
loss of LBM not related to reduced nutrient intake.
• Cannot be corrected solely by increasing the diet
• Common pathway leading to PEW is related to
exaggerated protein breakdown relative to protein
synthesis.
• A reduced muscle mass appears to be the most
valid criterion for the presence of PEW.

Expert panel from the International Society of Renal
Nutrition and Metabolism (ISRNM), Kidney Int 2008

Significance of PEW
• PEW is common in PD patients (16~60%).
• PEW is associated with increased risk of
morbidity & mortality.
• Early identification is the key to rehabilitating
malnourished dialysis patients and avoiding
poor outcome.

Two-Year Survival Probabilities
According to Nutritional Status
at Initiation of PD
Probability (%)
90
80
70
60
50
40
30
20
10
0
47
77
81
100
90
80
70
60
50
40
30
20
10
0
65
81
88
1-2 3-5 5-7
73
SGA
% LBM
CANUSA Peritoneal Dialysis Study Group, 1996

Malnutrition is an Independent Predictor of
Poor Survival in Asian CAPD Patients
Incident patient
2 year patient survival
SGA Normal : 91.7%
SGA Malnutrition : 67.1%
Prevalent patient
1 year patient survival
CNI 10 or below : 92%
CNI 11 or above : 86.6%
normal
Percent surviving
malnutrition
Months on CAPD
Chung SH et al, PDI 20;19,2000 Lo WK et al, PDI 21;441,2001

What are the Causes of
PEW in PD Patients?

Causes of PEW in PD Patients
Inadequate Nutrient Intake
• Inadequate nutrient intake is probably the
most important single cause of PEW.
• Anorexia is the most important cause of
reduced nutrient intake.
• Multiple causes of anorexia, underdialysis
most important.

Anorectic Factors in PD Patients
Effects Induced by Peritoneal Dialysis Per Se
• Abdominal discomfort induced by dialysate
• Absorption of glucose and amino acids from the dialysate
• Peritonitis
General Factors
• Uremic toxicity (underdialysis)
• Unpalatable or inadequate diets
• Gastropathy (in diabetics)
• Medications
• Psychosocial factors such as poverty, loneliness, and
depression
Lindholm B et al, NDT 1998;13(Suppl6):66-73

Dietary Intake of CAPD Patients
vs. Age- & Sex-Matched Controls
Controls
(n=249)
CAPD pts
(n=249)
Dietary energy input (kcal/kg/d) 33.3±10.4 24.7±8.7*
Total energy input including PD glucose
(kcal)*
Total energy input including PD glucose
(kcal/kg/d)*
1991±584 1620±457*
NA 28.4±8.7
Protein (g/kg/d) 1.52±0.56 1.10±0.45*
Fat (g/kg/d) 1.05±0.44 0.82±0.37*
Carbohydrate (g/kg/d) 4.52±1.42 3.25±1.25*
• Dietary intake estimated by 7day-FFQ (Food frequency questionnaires)
• *P

Multi-Factorial Causes of Malnutrition
Dietary protein
& energy intake
Peritoneal transport
Dialysis dose
Metabolic acidosis
Nutrition
in
PD Patients
Residual renal
function
Comorbidity
Inflammation
Infection
PD duration

Expert panel from the ISRNM, Kidney Int 2008

How to Assess
Nutritional Status in PD
Patients?

Guideline 1 - Use of Panels of
Nutritional Measures
Nutritional status in maintenance dialysis
patients should be assessed with a
combination of valid complementary measures
rather than any single measure alone.
Rationale: No single measure provides a
comprehensive indication of nutrition status.
Measures of intake, visceral and somatic protein
stores, body composition, and functional status identify
different aspects of nutrition status.
NKF-DOQI, Nutrition Practice Guidelines

Guideline 2 - Panels of Nutrition Measures
for Maintenance Dialysis (MD) Patients
Nutritional status in MD patients should be routinely
assessed using SA, % BW, % Standard BW, SGA,
dietary interviews/ diaries, and nPNA. (O)
Rationale: These measures provide a valid and clinically
useful characterization of the P-E nutrition status of MD
patients.
Frequency: Monthly-SA, HD nPNA, % dry wt; Q4 mo-
%standard BW, PD nPNA; Biannually-SGA, Diet
interview/diary; As needed-anthropometrics, DEXA, PAB, Cr
index
NKF-DOQI, Nutrition Practice Guidelines

European Best Practice Guidelines for Nutritional
Parameter Monitoring in HD and PD Patients
Heng AE and Cano NJM, NDT Plus 2010

Strong Correlation between Handgrip
Strengths and Lean Body Mass by
Creatinine Kinetics in PD Patients
Lean body mass by creatinine kinetics (kg)
Handgrip strength (kg)
Overall: R=0.603, P

Handgrip Strength as an Independent
Prognostic Indicator in PD Patients
Kaplan-Meier Survival Curves for Overall Survival
P

A Simple Question About Appetite is a
Powerful Predictor of Outcome

Readily utilizable criteria for the clinical
diagnosis of PEW in AKI or CKD
Expert panel from the ISRNM, Kidney Int 2008

Readily utilizable criteria for the clinical
diagnosis of PEW in AKI or CKD
Expert panel from the ISRNM, Kidney Int 2008

What Can be Done to Prevent or
Treat Protein-Energy Wasting
in Dialysis Patients?

Prevention and Treatment of Protein-
Energy Wasting in PD Patients
Routine Management
• Maintain adequate dialysis dose
• Preserve RRF
• Prevent PEM before the onset of MD therapy
• Maintain optimal nutrition
- Careful, regular monitoring of nutritional status
- Nutritional counseling
- Nutritional supplement (oral, enteral, or parenteral)
• Avoid volume overload and acidemia
• Aggressive treatment of catabolic illness

Recommendations for Protein and Energy
Supply in Dialysis Patients
ESPEN NKF EBPG
Protein intake
(g/kg/day) (HD)
Protein intake
(g/kg/day) (PD)
1.2-1.4 (>50% HBV) 1.2 (>50% HBV) ≥1.1
1.2-1.5 (>50% HBV) 1.2-1.3 (>50% HBV) 1.3
Energy intake
(kcal/kg/day) (HD)
35

Oral Nutritional Supplementation in PD
Patients – Does It Work?
• 7 clinical trials in PD patients
• Mixed results – disappointing !!
• Serum albumin is the most common primary
outcome
• Problems with study design: Power/sample size
• Noncompliance & compensation
Boudville N, Perit Dial Int 25: 157-160, 2005

In the study group, oral administration of the egg albumin
based supplement significantly improved serum albumin,
calorie and protein intake, and nPNA, and, compared to
controls, this maneuver was associated with a trend to
increased anthropometric parameters and improved SGA
evaluation.
Perit Dial Int 2005

Protenplus proved to be unsuitable as a long term, oral
protein-energy supplement in PD patients due to a high
rate of noncompliance and intolerance, primarily among
patients with lower residual renal function.
Perit Dial Int 2005

Prevention and Treatment of Protein-
Energy Wasting in PD Patients
PD-related
• Avoid potential sources of inflammation during the
PD procedure
- Peritonitis
- Biocompatible PD solutions
• Maintain optimal fluid balance
• Use PD solutions containing amino acids

Long-term Effects of IPAA
in CAPD Patients
• 3-year, prospective randomized study in malnourished
patients
• Nutrineal group (DAA, n=30) vs. control group (DD, n=30)
• Composite nutritional index remained stable & were not
different.
• S-albumin decreased lesser in DAA group.
• DPI increased in DAA group.
• LBM of female-DD decreased, but remained stable in
female-DAA. No changes in male.
• Mortality, hospitalization, and drop-out rates were not
different.
F. K. Li et al, Am J Kidney Dis 42:173-183 2003

Serial Changes in Lean Body Mass (LBM)
and Body Mass Index (BMI) for Male
: Control
• : Nutrineal
F. K. Li et al, Am J Kidney Dis 42:173-183 2003

Serial Changes in Lean Body Mass (LBM)
and Body Mass Index (BMI) for Female
* P < 0.05 vs. control
: Control
• : Nutrineal
F. K. Li et al, Am J Kidney Dis 42:173-183 2003

Dialysate as Food: Combined Amino Acid and
Glucose Dialysate Improves Protein Anabolism in
Renal Failure Patients on APD
• A random-order cross-over study in two periods of 7 day
each
• Cycler-assisted mixing of one bag of Nutrineal + four bags
of Physioneal (AAG) vs. five bags of Physioneal (G)
• Net protein balance increased in all AAG patients
• 24-hr nitrogen balance improved in 6/8 patients
Tjiong HL et al, J Am Soc Nephrol 16: 1486-1493, 2005

Dialysate that contains amino acids plus glucose also
improves protein synthesis in fed CAPD patients. The use
of such a mixture may contribute to long-term
improvement of the nutritional status in malnourished
CAPD patients with deficient food intake.
Tjiong et al, CJASN 2007

Prevention and Treatment of Protein-
Energy Wasting in PD Patients
• Use appetite stimulants
Nontraditional
• Encourage anti-inflammatory diets
- Dietary phytoestrogens, dietary fiber, omega-3
fatty acids, glycation end-product inhibitors
• Provide anti-inflammatory treatment
- Statins, glycation end-product inhibitors, PPARgamma
agonists, antioxidants
• Anti-cytokine treatment

Conclusion
• It is still not clear whether obesity leads to better
or worse survival in PD patients. However, PD
patients should be encouraged to gain muscle
mass rather than fat mass.
• PEW is among the strongest predictors of a poor
outcome in these patients – but few successful
interventional studies.
• Early identification of patients at risk of PEW is
important.
• Active monitoring of nutritional status and
attempts to prevent PEW are strongly
recommended.