Effectives of Nutritional Interventions in CKD/HD
Alison Steiber PhD, RD Chief Science Officer
Academy of Nutrition and Dietetics [email protected]
Adjunct Professor Department of Nutrition,
Case Western Reserve University 10900 Euclid Ave,
Cleveland, OH 44120
The Evidence Based Practice Cycle
Clinical Practice
Evidence Based
Practice Guidelines
Outcomes Research
Monitoring & Evaluation
Assessment
Diagnosis
Intervention
IDNT
Translational Research
Congress, CMS,
Insurance
Nutrition Care Process
Assessment
Diagnosis: ID Nutrition
Problem
Intervention
Monitor, Measure & Evaluation
Protein-Energy Wasting
Fouque et al, JASON, 2007
Suboptimal status of Macronutrients
05
101520253035404550
Perc
ent
SGA1SGA2
SGA3SGA4
SGA5SGA6
SGA7
baseline 1 month 6 months
n=154, Steiber et al, JREN, 2007
At baseline – 70% with some degree of nutritional loss
Diagnosis Protein Energy Wasting
Fouque, et al, KI, 2008
1 BCH parameter included
Note cut-point, may not be suitable in all
populations
Malnutrition Characteristics Energy Intake Weight Loss Body Fat Muscle Loss Fluid accumulation Reduced Grip Strength
Definition = a minimum of 2 characteristics present
Diagnosis of Etiology-based Malnutrition
Consequences: Hospitalizations
n = 101, p=0.06, Steiber et al, unpublished
Consequences: Mortality
9
de Musert et al, AJCN, 2009
SGA in the Hospital: Predicts mortality
Lim et al, Clinical Nutrition, 2012
• Singapore Hospital population
• 818 total patients • 235 malnourished • SGA used to assess nutrition
status
PEW Non-PEW
90 day Mortality & Readmission
MST SGA = Diagnosis of malnutrition
Agarwal et al, Clinical Nutrition, 2012
Suboptimal status of Micronutrients
Singer et al, Nephrology, 2008
Vitamin K
Suboptimal status of micronutrients
Schlieper et al, JASON, 2011
Consequences: Mortality
Schlieper et al, JASON, 2011
Progression of wasting
15
Obermayer, NDT, 2009
ESRD = catabolic = wasting
Kalantar-Zadeh et al, KI, 2003
Nutrition Care Process
Assessment
Diagnosis: ID Nutrition
Problem
Intervention
Monitor, Measure & Evaluation
Food & Oral Nutrition Supplements
Vegetarian Hits the Main Stream
Vegetarian Safety
Bernstein et al, JADA, 2007
Conclusion on Safety: 1.Limited # of studies
2.In people with normal kidney fx, there dynamic changes in GFR after consumpt high animal protein but not with veg pro
3.Substituting veg protein or fish may pro against proteinuria
4.Long term consumption of high protein d healthy persons may cause renal inju
Vegetarian Diet in CKD Patients Mild CKD = CrCl range 40-20 ml/min/1.73m2
11 pts
• Unrestricted Protein Diet
11pts
• Specialized Vegetarian Diet
11 pts
• Conventional Low Protein Diet
11pts
• Specialized Vegetarian Diet
F/U at least 6 months
Barsotti et al, Nephrology 1996
No difference in Nutrition Status
Parameter Before SVD During SVD
Body weight (kg)
63.9+10.1 64.2+11.2
Serum total protein g/dl
7.1+0.6 7.2+0.6
Serum Albumin g/dl
4.0+0.5 4.1+0.5
Serum transferrin mg/dl
226+27 224+54
Ave length of time treated 13.4+5.4 months on SVD
Barsotti et al, Nephrology 1996
Nutrition status in HD Veg. vs. Non-Veg. Pts
Wu et al, Nephrology, 2011
The Phosphorus Issue:
Noori et al, IJKD, 2010
Vegetarian vs. Meat Diet Comparison
Moe et al, cJASN, 2011
n= 9 recruited, 8 completed
Components of a vegetarian diet with benefit:
Nuts Soy Antioxidants Fiber
Brazil Nuts
Stockler-Pinto et al, Nutrition, 2009
Oral Supplements MHD pts in txt grp given 1 can Oxepa & 1 can
Nepro each treatment
Kalantar-Zadeh, JREN, 2005
Oral Supplementation
-0.5
0
0.5
1
1.5
2
Hem
odia
lysi
s P
rogn
ostic
In
dex
Sco
re
PreHDPNI PostHDPN
ControlTreatment
-.3+.9
1.8+1.3
-.04+1.1
1.3+1.6
Steiber et al, JREN, 2003; p<0.05
Nutrition Intervention Intradialytic Parenteral Nutrition (IDPN)
IDPN in Acute Illness
Korzets, JRC, 2008
IDPN in Acute Illness
Korzets, JRC, 2008
Intradialytic Parenteral Nutrition Showed 6 months of AA supplement by IDPN
in 97 MHD pts
Czekalski, JREN, 2004
Intradialytic Parenteral Nutrition & Oral Supplements
Cano, JASON, 2007
Micronutrient Interventions
Interventions with vitamin C Meta- Analysis in Dialysis Patients - Improved Hgb with Vitamin C Treatment
Devedet al AJKD, 2009 3 clinical trials = 125 patients
Interventions with Vitamin C Meta- Analysis in Dialysis Patients - Decrease ESA with Vitamin C Treatment
Devedet al AJKD, 2009 5 clinical trials = 303 patients
• Baseline: • HD patients had 8.4-fold higher %ucOC levels • PIVKA-II levels were elevated in 49 HD
• Intervention: • 135 μg & 360 μg of menaquinone-7 (Vitamin K2)
• Post-Intervention = decrease in: • circulating d-uncarboxylated MGP, • %ucOC, and • PIVKA-II levels.
• Response rates in the reduction in d-uncarboxylated MGP levels were 77% & 93%
Intervention with Vitamin K
Westenfeld et al, AJKD, 2011 Epub
Intervention with Zinc
GUO, C, Nutrients, 2013
Intervention with Selenium
Salehi et al, NDT, 2013
Impact of Multivitamins on Mortality
DOPPS data = patients taking water-soluble vitamins had 16% mortality risk than patients not taking vitamins ◦ Adjusted for age, sex, race, co-morbid conditions, hemoglobin, serum albumin, body mass index, time on dialysis, ave. facility single-pool Kt/V and NPCR
Andreucci et al, AJKD, 2004
Interventions for Obesity
Treating Obesity in CKD Patients?
Non-randomized clinical trial, stage 3&4 CKD & dialysis Weight significantly decreased in WMP 35% of dialysis patients accepted for transplant list Study limits?
Small sample size No mortality data
Maclaughlin et al, AJKD, 2010
Weight loss in obese patients? Data at this point indicates the mortality
risk increases with: ◦ Unintentional Weight loss ◦ Lower BMI values ◦ Lower fat free mass Especially below 25
If a patient is considering applying for a transplant ◦ Work with team to determine whether weight loss is the best choice for the patient ◦ Consider both diet restriction & exercise to promote weight loss
Interventions for Inflammation
47
Steps to Inflammation Management
Carrero JJ and Stenvinkel P, et al. Seminars in Dialysis. 2010:23(5);498–509.
I. Evaluate and treat inter-current events and co-morbidities that may cause inflammation
• Infectious complications and intercurrent clinical events
• Silent ischemic heart disease • Periodontal disease
• Failed kidney transplant • Volume overload • Inflammatory diseases
48
Steps to Inflammation Management
Carrero JJ and Stenvinkel P, et al. Seminars in Dialysis. 2010:23(5);498–509.
II. Evaluate and, if possible, handle potential dialysis-related causes of inflammation
Peritoneal dialysis • Bioincompatible dialysis
fluids • Periotonitis • Exit-site infection • Volume overload • Glucose degradation products
Hemodialysis • Central dialysis catheter • Unpure dialysate • Infectious complications of
hemodialysis access • Thrombosed fistula or graft • Bioincompatible membranes • Hemodiafiltration • Volume overload
49
Steps to Inflammation Management
Carrero JJ and Stenvinkel P, et al. Seminars in Dialysis. 2010:23(5);498–509.
III. Consider possible anti-inflammatory treatment strategies
• Physical training • Nutritional
interventions • Omega-3 fatty acids • Gamma tocopherol • Soy isoflavones • Genistein
• Future treatment with anti-cytokine therapy
• IL-1 receptor antagonists
• Soluble TNF receptors • Antibodies again TNF • Chemokine
antagonism
• Non-specific immuno-modulation
• Statins • D-vitamin • ACEI/ARBs • Pentoxifylline • Heparin (?)
Decrease in CRP in Patients with High Baseline
0
1
2
3
4
5
0 1 2 3 4 5 6
Follow-up (months)
CRP
(mg/
dl)
Placebo Carnitine Placebo Carnitine
Savica, JREN, 2005
Trovato (2)
Bellinguieri (11)
Fagher (7-9)
overall effect
Labonia (17)
Patrikarea (18)
Megri (19)
Caruso (20)
Altmann (23)
Kletzmayr (22)
overall effect -3.5 -2.5 -1.5 -0.5 0.5 1.5
The effect of L-carnitine on anemia control (top; fixed model analysis) and erythropoietin dose reduction (bottom; random model analysis). Open boxes indicate the effect of each individual trial, and the closed boxes the overall effect of treatment. The P value is given for overall treatment effect and is significant for values ≤ 0.01. Heterogeneity of treatment effect among trials is present if H test value is < 0.10.
(95 % Cl: 0.02;1.00) p=0.01 Htest 0.20
(95 % Cl: -1.46;-0.05) p=0.01 Htest 0.20
Hurot JM, et al. J ASON 2002
Omega-3 Fatty Acids
Omega-3 Fatty Acids have been shown to have a positive impact on BP, low-density lipoproteins, and inflammation
Are metabolized to arachidonic and eicosapentaenoic acids ◦ Are precursors for anti-inflammatory compounds such
as Lipoxin Protectins Nitrolipids Resolvins
52 vonSchacky & Harris, Cardiovascular Research..2007. 73, 310-315. Serhan et al, Annu. Rev. Pathol. Mech Dis. 2008. 3, 279-312. Das, Lipids in Health and Disease. 2008. 7, 19-25
53
Clinical Trials with Omega-3
Svesson, et al. JASON. 2006:1;780–786. RCT with 206 patients assigned to either n-3 PUFA or Control 1.7 g/d of PUFA (45% EPA & 37% DHA): 2 year study
54
Clinical Trials with Omega-3
Bowden, et al. JREN. 2009:19(4);259–266. 6–1 g pills for 6 months, 160 mg EPA, 100 mg of DHA.
55
Clinical Trials with Omega-3
Hassan, et al. RF. 2010;32(9):1031–1035. 15 PD pts, 1.0 g EPA, 2.4 g DHA
Clinical Trial with Unsaturated Fat Supplement
56
Ewers, et al. JREN. 2009;19(5):401–411. cross-over design, 14 patients, * = p<0.05 from non-supplemented period
Impact of Nutrition Care
Aka the RDN…
Prevalence of a patient on HD seeing a Dietitian (RD)
36
84
26
0
10
20
30
40
50
60
70
80
90
Saw an RD*
Europe/AUS/NZNAJapan
* Saw dietitian in prior 6 months (%); Lopes A, et al, JREN, 2010
Impact of RD Interventions
0.95
0.85
1 1
0.87
0.75
0.8
0.85
0.9
0.95
1
1.05
RD (yes/no)
CreatinineAlbuminBMInPCRCachectic<3.5 vs >3.5 Yes vs No
* *
* = statistically significant, Lopes A et al, JREN, 2010
Thank You!