in PD Patients - APCN 2010
in PD Patients - APCN 2010
in PD Patients - APCN 2010
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Peritoneal Dialysis and Nutrition<br />
Seung Hyeok Han, MD, PhD<br />
Dae-Suk Han, MD, PhD<br />
Department of Internal Medic<strong>in</strong>e,<br />
Yonsei University College of Medic<strong>in</strong>e, Seoul, Korea
Nutritional Problems <strong>in</strong><br />
Dialysis <strong>Patients</strong><br />
• Prote<strong>in</strong>-energy wast<strong>in</strong>g (PEW)<br />
• Overweight / obesity<br />
• Metabolic syndrome
Metabolic Syndrome (MeS) <strong>in</strong> <strong>PD</strong> <strong>Patients</strong><br />
• Higher prevalence <strong>in</strong> <strong>PD</strong> (50%) than <strong>in</strong> HD<br />
(20%) and predialysis (30%) patients<br />
• Asian <strong>PD</strong> patients<br />
- 53.3% <strong>in</strong> Hong Kong<br />
- 55% <strong>in</strong> Taiwan<br />
- 47.2% <strong>in</strong> Korea<br />
• MeS is an <strong>in</strong>dependent risk factor of mortality <strong>in</strong><br />
non-diabetic <strong>PD</strong> patients.<br />
• Not clear whether the use of a diagnosis of MeS<br />
would be better than us<strong>in</strong>g each risk factors<br />
separately as a predictor of CVD <strong>in</strong> <strong>PD</strong> patients.
MeS Predicts Mortality <strong>in</strong> Non-Diabetic<br />
<strong>PD</strong> <strong>Patients</strong><br />
Park et al, NDT <strong>2010</strong>
<strong>PD</strong> and Obesity<br />
• <strong>Patients</strong> commonly ga<strong>in</strong> weight post-<strong>PD</strong>,<br />
particularly <strong>in</strong> the first year of <strong>PD</strong>.<br />
• Some patients may have excessive weight ga<strong>in</strong><br />
(more than 10 kg).<br />
• Ma<strong>in</strong>ly due to <strong>in</strong>crease <strong>in</strong> fat mass <strong>in</strong>clud<strong>in</strong>g<br />
the abdom<strong>in</strong>al fat.<br />
• No significant relation between peritoneal<br />
glucose absorption and changes <strong>in</strong> fat mass.<br />
• By BMI, 50.9% of prevalent <strong>PD</strong> patients were<br />
overweight (BMI > 25 kg/m 2 )
Consequences of Obesity<br />
• Higher risk of peritonitis and technique failure<br />
• Risk of further weight ga<strong>in</strong><br />
• More rapid loss of RRF<br />
• Risk of <strong>in</strong>adequate dialysis<br />
• Impact on outcomes
Is It Good to be Fat <strong>in</strong><br />
Dialysis <strong>Patients</strong> ?<br />
• Numerous observational studies suggest that<br />
higher BMI is associated with better outcome <strong>in</strong> HD.<br />
• However, association of BMI with outcomes is<br />
controversial <strong>in</strong> <strong>PD</strong> patients.<br />
• Better survival - Johnson et al, <strong>PD</strong>I 2000<br />
Snyder et al, KI 2003<br />
• Higher risk of death - McDonald et al, JASN 2003<br />
Stack et al, KI 2004
Should Dialysis <strong>Patients</strong> be<br />
Encouraged to Become Obese?
Association Between BMI and Mortality is<br />
Similar <strong>in</strong> HD and General Population at High<br />
Age and Equal Duration of F/U
Both Body Size and Body Composition<br />
Influence Survival of Incident <strong>PD</strong> <strong>Patients</strong><br />
Body composition group HR for All-Cause Death HR for CV Death<br />
Normal BMI (18.5-24.9 kg/m 2 )<br />
and Ucr > 0.64 g/day<br />
Reference<br />
Reference<br />
Normal BMI (18.5-24.9 kg/m 2 )<br />
and Ucr ≤ 0.64 g/day<br />
High BMI (≥ 25 kg/m 2 )<br />
and Ucr > 0.64 g/day<br />
High BMI (≥ 25 kg/m 2 )<br />
and Ucr ≤ 0.64 g/day<br />
1.20 (1.09-1.31) 1.22 (1.08-1.38)<br />
0.90 (0.83-0.97) 0.88 (0.79-0.97)<br />
1.29 (1.17-1.42) 1.21 (1.06-1.39)<br />
Ramkumar et al, <strong>PD</strong>I 2005
Obese Sarcopenia <strong>in</strong> ESRD <strong>Patients</strong> is<br />
Assoicated with Inflammation and<br />
Increased Mortality<br />
• PEW was present <strong>in</strong> 60% of patients with BMI < 20<br />
kg/m 2 , 39% with BMI 20-25 kg/m 2 .<br />
• Overweight patients (BMI > 25 kg/m 2 ) also had high<br />
prevalence of PEW (16%).<br />
• Obese sarcopenia group had highest levels of IL-6,<br />
CRP, and fat body mass <strong>in</strong>dex, and FBMI/LBMI<br />
ratio.<br />
• For each BMI group, the presence of PEW was<br />
associated with <strong>in</strong>creased mortality.<br />
Honda et al, Am J Cl<strong>in</strong> Nutr 2007
The Muscle Matters, Not the Fat
Obesity and Prote<strong>in</strong>-Energy Wast<strong>in</strong>g <strong>in</strong> <strong>PD</strong><br />
<strong>Patients</strong> is a Two-Dimensional Problem<br />
• Nutritional problems <strong>in</strong> <strong>PD</strong> patients cannot be<br />
merely classified on the basis of BMI.<br />
• High body mass <strong>in</strong> the presence of low muscle<br />
mass and PEW underlies a high death risk (obese<br />
sarcopenia).<br />
• Prognostic value of nutritional status <strong>in</strong> <strong>PD</strong> patients<br />
should be based on BMI and muscle mass and/or<br />
prote<strong>in</strong>-energy balance.
Malnutrition<br />
• Refers to abnormalities <strong>in</strong>duced by low nutrient<br />
<strong>in</strong>take or <strong>in</strong>take that is <strong>in</strong>adequate for the nutritional<br />
needs of the <strong>in</strong>dividual<br />
• Results <strong>in</strong> altered metabolism, impaired function,<br />
and reduced body mass<br />
• Can be corrected by <strong>in</strong>creas<strong>in</strong>g the diet
Prote<strong>in</strong>-Energy Wast<strong>in</strong>g (PEW)<br />
• State of decreased body store of prote<strong>in</strong> and<br />
energy fuels (body prote<strong>in</strong> and fat mass)<br />
• In kidney disease, there are conditions result<strong>in</strong>g <strong>in</strong><br />
loss of LBM not related to reduced nutrient <strong>in</strong>take.<br />
• Cannot be corrected solely by <strong>in</strong>creas<strong>in</strong>g the diet<br />
• Common pathway lead<strong>in</strong>g to PEW is related to<br />
exaggerated prote<strong>in</strong> breakdown relative to prote<strong>in</strong><br />
synthesis.<br />
• A reduced muscle mass appears to be the most<br />
valid criterion for the presence of PEW.
Expert panel from the International Society of Renal<br />
Nutrition and Metabolism (ISRNM), Kidney Int 2008
Significance of PEW<br />
• PEW is common <strong>in</strong> <strong>PD</strong> patients (16~60%).<br />
• PEW is associated with <strong>in</strong>creased risk of<br />
morbidity & mortality.<br />
• Early identification is the key to rehabilitat<strong>in</strong>g<br />
malnourished dialysis patients and avoid<strong>in</strong>g<br />
poor outcome.
Two-Year Survival Probabilities<br />
Accord<strong>in</strong>g to Nutritional Status<br />
at Initiation of <strong>PD</strong><br />
Probability (%)<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
20<br />
10<br />
0<br />
47<br />
77<br />
81<br />
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
20<br />
10<br />
0<br />
65<br />
81<br />
88<br />
1-2 3-5 5-7<br />
73<br />
SGA<br />
% LBM<br />
CANUSA Peritoneal Dialysis Study Group, 1996
Malnutrition is an Independent Predictor of<br />
Poor Survival <strong>in</strong> Asian CA<strong>PD</strong> <strong>Patients</strong><br />
Incident patient<br />
2 year patient survival<br />
SGA Normal : 91.7%<br />
SGA Malnutrition : 67.1%<br />
Prevalent patient<br />
1 year patient survival<br />
CNI 10 or below : 92%<br />
CNI 11 or above : 86.6%<br />
normal<br />
Percent surviv<strong>in</strong>g<br />
malnutrition<br />
Months on CA<strong>PD</strong><br />
Chung SH et al, <strong>PD</strong>I 20;19,2000 Lo WK et al, <strong>PD</strong>I 21;441,2001
What are the Causes of<br />
PEW <strong>in</strong> <strong>PD</strong> <strong>Patients</strong>?
Causes of PEW <strong>in</strong> <strong>PD</strong> <strong>Patients</strong><br />
Inadequate Nutrient Intake<br />
• Inadequate nutrient <strong>in</strong>take is probably the<br />
most important s<strong>in</strong>gle cause of PEW.<br />
• Anorexia is the most important cause of<br />
reduced nutrient <strong>in</strong>take.<br />
• Multiple causes of anorexia, underdialysis<br />
most important.
Anorectic Factors <strong>in</strong> <strong>PD</strong> <strong>Patients</strong><br />
Effects Induced by Peritoneal Dialysis Per Se<br />
• Abdom<strong>in</strong>al discomfort <strong>in</strong>duced by dialysate<br />
• Absorption of glucose and am<strong>in</strong>o acids from the dialysate<br />
• Peritonitis<br />
General Factors<br />
• Uremic toxicity (underdialysis)<br />
• Unpalatable or <strong>in</strong>adequate diets<br />
• Gastropathy (<strong>in</strong> diabetics)<br />
• Medications<br />
• Psychosocial factors such as poverty, lonel<strong>in</strong>ess, and<br />
depression<br />
L<strong>in</strong>dholm B et al, NDT 1998;13(Suppl6):66-73
Dietary Intake of CA<strong>PD</strong> <strong>Patients</strong><br />
vs. Age- & Sex-Matched Controls<br />
Controls<br />
(n=249)<br />
CA<strong>PD</strong> pts<br />
(n=249)<br />
Dietary energy <strong>in</strong>put (kcal/kg/d) 33.3±10.4 24.7±8.7*<br />
Total energy <strong>in</strong>put <strong>in</strong>clud<strong>in</strong>g <strong>PD</strong> glucose<br />
(kcal)*<br />
Total energy <strong>in</strong>put <strong>in</strong>clud<strong>in</strong>g <strong>PD</strong> glucose<br />
(kcal/kg/d)*<br />
1991±584 1620±457*<br />
NA 28.4±8.7<br />
Prote<strong>in</strong> (g/kg/d) 1.52±0.56 1.10±0.45*<br />
Fat (g/kg/d) 1.05±0.44 0.82±0.37*<br />
Carbohydrate (g/kg/d) 4.52±1.42 3.25±1.25*<br />
• Dietary <strong>in</strong>take estimated by 7day-FFQ (Food frequency questionnaires)<br />
• *P
Multi-Factorial Causes of Malnutrition<br />
Dietary prote<strong>in</strong><br />
& energy <strong>in</strong>take<br />
Peritoneal transport<br />
Dialysis dose<br />
Metabolic acidosis<br />
Nutrition<br />
<strong>in</strong><br />
<strong>PD</strong> <strong>Patients</strong><br />
Residual renal<br />
function<br />
Comorbidity<br />
Inflammation<br />
Infection<br />
<strong>PD</strong> duration
Expert panel from the ISRNM, Kidney Int 2008
How to Assess<br />
Nutritional Status <strong>in</strong> <strong>PD</strong><br />
<strong>Patients</strong>?
Guidel<strong>in</strong>e 1 - Use of Panels of<br />
Nutritional Measures<br />
Nutritional status <strong>in</strong> ma<strong>in</strong>tenance dialysis<br />
patients should be assessed with a<br />
comb<strong>in</strong>ation of valid complementary measures<br />
rather than any s<strong>in</strong>gle measure alone.<br />
Rationale: No s<strong>in</strong>gle measure provides a<br />
comprehensive <strong>in</strong>dication of nutrition status.<br />
Measures of <strong>in</strong>take, visceral and somatic prote<strong>in</strong><br />
stores, body composition, and functional status identify<br />
different aspects of nutrition status.<br />
NKF-DOQI, Nutrition Practice Guidel<strong>in</strong>es
Guidel<strong>in</strong>e 2 - Panels of Nutrition Measures<br />
for Ma<strong>in</strong>tenance Dialysis (MD) <strong>Patients</strong><br />
Nutritional status <strong>in</strong> MD patients should be rout<strong>in</strong>ely<br />
assessed us<strong>in</strong>g SA, % BW, % Standard BW, SGA,<br />
dietary <strong>in</strong>terviews/ diaries, and nPNA. (O)<br />
Rationale: These measures provide a valid and cl<strong>in</strong>ically<br />
useful characterization of the P-E nutrition status of MD<br />
patients.<br />
Frequency: Monthly-SA, HD nPNA, % dry wt; Q4 mo-<br />
%standard BW, <strong>PD</strong> nPNA; Biannually-SGA, Diet<br />
<strong>in</strong>terview/diary; As needed-anthropometrics, DEXA, PAB, Cr<br />
<strong>in</strong>dex<br />
NKF-DOQI, Nutrition Practice Guidel<strong>in</strong>es
European Best Practice Guidel<strong>in</strong>es for Nutritional<br />
Parameter Monitor<strong>in</strong>g <strong>in</strong> HD and <strong>PD</strong> <strong>Patients</strong><br />
Heng AE and Cano NJM, NDT Plus <strong>2010</strong>
Strong Correlation between Handgrip<br />
Strengths and Lean Body Mass by<br />
Creat<strong>in</strong><strong>in</strong>e K<strong>in</strong>etics <strong>in</strong> <strong>PD</strong> <strong>Patients</strong><br />
Lean body mass by creat<strong>in</strong><strong>in</strong>e k<strong>in</strong>etics (kg)<br />
Handgrip strength (kg)<br />
Overall: R=0.603, P
Handgrip Strength as an Independent<br />
Prognostic Indicator <strong>in</strong> <strong>PD</strong> <strong>Patients</strong><br />
Kaplan-Meier Survival Curves for Overall Survival<br />
P
A Simple Question About Appetite is a<br />
Powerful Predictor of Outcome
Readily utilizable criteria for the cl<strong>in</strong>ical<br />
diagnosis of PEW <strong>in</strong> AKI or CKD<br />
Expert panel from the ISRNM, Kidney Int 2008
Readily utilizable criteria for the cl<strong>in</strong>ical<br />
diagnosis of PEW <strong>in</strong> AKI or CKD<br />
Expert panel from the ISRNM, Kidney Int 2008
What Can be Done to Prevent or<br />
Treat Prote<strong>in</strong>-Energy Wast<strong>in</strong>g<br />
<strong>in</strong> Dialysis <strong>Patients</strong>?
Prevention and Treatment of Prote<strong>in</strong>-<br />
Energy Wast<strong>in</strong>g <strong>in</strong> <strong>PD</strong> <strong>Patients</strong><br />
Rout<strong>in</strong>e Management<br />
• Ma<strong>in</strong>ta<strong>in</strong> adequate dialysis dose<br />
• Preserve RRF<br />
• Prevent PEM before the onset of MD therapy<br />
• Ma<strong>in</strong>ta<strong>in</strong> optimal nutrition<br />
- Careful, regular monitor<strong>in</strong>g of nutritional status<br />
- Nutritional counsel<strong>in</strong>g<br />
- Nutritional supplement (oral, enteral, or parenteral)<br />
• Avoid volume overload and acidemia<br />
• Aggressive treatment of catabolic illness
Recommendations for Prote<strong>in</strong> and Energy<br />
Supply <strong>in</strong> Dialysis <strong>Patients</strong><br />
ESPEN NKF EBPG<br />
Prote<strong>in</strong> <strong>in</strong>take<br />
(g/kg/day) (HD)<br />
Prote<strong>in</strong> <strong>in</strong>take<br />
(g/kg/day) (<strong>PD</strong>)<br />
1.2-1.4 (>50% HBV) 1.2 (>50% HBV) ≥1.1<br />
1.2-1.5 (>50% HBV) 1.2-1.3 (>50% HBV) 1.3<br />
Energy <strong>in</strong>take<br />
(kcal/kg/day) (HD)<br />
35<br />
Oral Nutritional Supplementation <strong>in</strong> <strong>PD</strong><br />
<strong>Patients</strong> – Does It Work?<br />
• 7 cl<strong>in</strong>ical trials <strong>in</strong> <strong>PD</strong> patients<br />
• Mixed results – disappo<strong>in</strong>t<strong>in</strong>g !!<br />
• Serum album<strong>in</strong> is the most common primary<br />
outcome<br />
• Problems with study design: Power/sample size<br />
• Noncompliance & compensation<br />
Boudville N, Perit Dial Int 25: 157-160, 2005
In the study group, oral adm<strong>in</strong>istration of the egg album<strong>in</strong><br />
based supplement significantly improved serum album<strong>in</strong>,<br />
calorie and prote<strong>in</strong> <strong>in</strong>take, and nPNA, and, compared to<br />
controls, this maneuver was associated with a trend to<br />
<strong>in</strong>creased anthropometric parameters and improved SGA<br />
evaluation.<br />
Perit Dial Int 2005
Protenplus proved to be unsuitable as a long term, oral<br />
prote<strong>in</strong>-energy supplement <strong>in</strong> <strong>PD</strong> patients due to a high<br />
rate of noncompliance and <strong>in</strong>tolerance, primarily among<br />
patients with lower residual renal function.<br />
Perit Dial Int 2005
Prevention and Treatment of Prote<strong>in</strong>-<br />
Energy Wast<strong>in</strong>g <strong>in</strong> <strong>PD</strong> <strong>Patients</strong><br />
<strong>PD</strong>-related<br />
• Avoid potential sources of <strong>in</strong>flammation dur<strong>in</strong>g the<br />
<strong>PD</strong> procedure<br />
- Peritonitis<br />
- Biocompatible <strong>PD</strong> solutions<br />
• Ma<strong>in</strong>ta<strong>in</strong> optimal fluid balance<br />
• Use <strong>PD</strong> solutions conta<strong>in</strong><strong>in</strong>g am<strong>in</strong>o acids
Long-term Effects of IPAA<br />
<strong>in</strong> CA<strong>PD</strong> <strong>Patients</strong><br />
• 3-year, prospective randomized study <strong>in</strong> malnourished<br />
patients<br />
• Nutr<strong>in</strong>eal group (DAA, n=30) vs. control group (DD, n=30)<br />
• Composite nutritional <strong>in</strong>dex rema<strong>in</strong>ed stable & were not<br />
different.<br />
• S-album<strong>in</strong> decreased lesser <strong>in</strong> DAA group.<br />
• DPI <strong>in</strong>creased <strong>in</strong> DAA group.<br />
• LBM of female-DD decreased, but rema<strong>in</strong>ed stable <strong>in</strong><br />
female-DAA. No changes <strong>in</strong> male.<br />
• Mortality, hospitalization, and drop-out rates were not<br />
different.<br />
F. K. Li et al, Am J Kidney Dis 42:173-183 2003
Serial Changes <strong>in</strong> Lean Body Mass (LBM)<br />
and Body Mass Index (BMI) for Male<br />
: Control<br />
• : Nutr<strong>in</strong>eal<br />
F. K. Li et al, Am J Kidney Dis 42:173-183 2003
Serial Changes <strong>in</strong> Lean Body Mass (LBM)<br />
and Body Mass Index (BMI) for Female<br />
* P < 0.05 vs. control<br />
: Control<br />
• : Nutr<strong>in</strong>eal<br />
F. K. Li et al, Am J Kidney Dis 42:173-183 2003
Dialysate as Food: Comb<strong>in</strong>ed Am<strong>in</strong>o Acid and<br />
Glucose Dialysate Improves Prote<strong>in</strong> Anabolism <strong>in</strong><br />
Renal Failure <strong>Patients</strong> on A<strong>PD</strong><br />
• A random-order cross-over study <strong>in</strong> two periods of 7 day<br />
each<br />
• Cycler-assisted mix<strong>in</strong>g of one bag of Nutr<strong>in</strong>eal + four bags<br />
of Physioneal (AAG) vs. five bags of Physioneal (G)<br />
• Net prote<strong>in</strong> balance <strong>in</strong>creased <strong>in</strong> all AAG patients<br />
• 24-hr nitrogen balance improved <strong>in</strong> 6/8 patients<br />
Tjiong HL et al, J Am Soc Nephrol 16: 1486-1493, 2005
Dialysate that conta<strong>in</strong>s am<strong>in</strong>o acids plus glucose also<br />
improves prote<strong>in</strong> synthesis <strong>in</strong> fed CA<strong>PD</strong> patients. The use<br />
of such a mixture may contribute to long-term<br />
improvement of the nutritional status <strong>in</strong> malnourished<br />
CA<strong>PD</strong> patients with deficient food <strong>in</strong>take.<br />
Tjiong et al, CJASN 2007
Prevention and Treatment of Prote<strong>in</strong>-<br />
Energy Wast<strong>in</strong>g <strong>in</strong> <strong>PD</strong> <strong>Patients</strong><br />
• Use appetite stimulants<br />
Nontraditional<br />
• Encourage anti-<strong>in</strong>flammatory diets<br />
- Dietary phytoestrogens, dietary fiber, omega-3<br />
fatty acids, glycation end-product <strong>in</strong>hibitors<br />
• Provide anti-<strong>in</strong>flammatory treatment<br />
- Stat<strong>in</strong>s, glycation end-product <strong>in</strong>hibitors, PPARgamma<br />
agonists, antioxidants<br />
• Anti-cytok<strong>in</strong>e treatment
Conclusion<br />
• It is still not clear whether obesity leads to better<br />
or worse survival <strong>in</strong> <strong>PD</strong> patients. However, <strong>PD</strong><br />
patients should be encouraged to ga<strong>in</strong> muscle<br />
mass rather than fat mass.<br />
• PEW is among the strongest predictors of a poor<br />
outcome <strong>in</strong> these patients – but few successful<br />
<strong>in</strong>terventional studies.<br />
• Early identification of patients at risk of PEW is<br />
important.<br />
• Active monitor<strong>in</strong>g of nutritional status and<br />
attempts to prevent PEW are strongly<br />
recommended.