effectives of nutritional interventions in...

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n = 101, p=0.06, Steiber et al, unpublished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

Presenter

Presentation Notes

PIVKA-II levels are indicators of Vit K def – higher is worse…it is a liver protein induced by vitamin k absence Study had a 188 dialysis patients – 64% were deficient per PIVKAII

Consequences: Mortality

Schlieper et al, JASON, 2011

Presenter

Presentation Notes

Left = all cause mortality and right = CVD mortality

Progression of wasting

15

Obermayer, NDT, 2009

Presenter

Presentation Notes

Vienna Health Screening Initiative – longitudinal cohort study 1990-2006, 49,398 volunteers Mild CKD = 2487 subjects Moderate CKD = 392

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

Presenter

Presentation Notes

Stockler Pinto: 81 HD patients enrolled in Rio Each patient received 1 nut (5g = 290mg of Se) per day x 3 months

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

Presenter

Presentation Notes

No real measure of inflammation

Nutrition Intervention Intradialytic Parenteral Nutrition (IDPN)

IDPN in Acute Illness

Korzets, JRC, 2008

Presenter

Presentation Notes

Supplemental and not total nutrition support – patients in this study were hypoalbumenic and catabolic, 1 bag, continuous infusion connected to the venous side, BG monitor discretion of nephrologist – acute illness = amputations, major infection, chemotherapy – 22 patients in study analysis – vitamin supplementation on a weekly basis

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

Presenter

Presentation Notes

French Intradialytic Nutrition Evaluation Study

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

Presenter

Presentation Notes

Ferritin was not significantly improved but t-sat was significantly improved

• 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

Presenter

Presentation Notes

to investigate whether daily vitamin K supplementation improves the bioactivity of vitamin K-dependent proteins in hemodialysis patients, assessed by circulating dephosphorylated-uncarboxylated MGP, uncarboxylated osteocalcin, and uncarboxylated prothrombin (PIVKA-II [protein induced by vitamin K absence II]). 53 HD pts and 50 age matched controls Gave vitamin K(2) = menenquionone 7 at 45, 135 and 360 micrograms/d x 6 weeks

Intervention with Zinc

GUO, C, Nutrients, 2013

Presenter

Presentation Notes

Zn deficient- with elevated Al CAPD and HD patients divided into high Al (24) or normal al (20) and compared with health subjects (25) – supplemented with 11 mg elemental Zn/pay = 78 mg Zn gluconate Reactive oxygen species (ROS) Superoxide dismutase (SOD) Malondialldehyde (MDA)

Intervention with Selenium

Salehi et al, NDT, 2013

Presenter

Presentation Notes

3 month, RCT DB 80 pts - intervention grp = 200 microg Se, nS difference at baseline in characteristics SGA was treated differently where A, B C was converted into number equivalents so that a lower score equaled better nutrition

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

Presenter

Presentation Notes

Used DR, exercise and orlist to promote weight loss in WMP

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

Presenter

Presentation Notes

Slide 1 shows you what we will be discussing today. First, the role and anatomy of the kidney. Then, we will look at chronic kidney disease, its causes and the various stages, as well as the incidence and prevalence. We will talk about nutrition in CKD, malnutrition and protein energy wasting, some nutritional recommendations, and the role of nutrition intervention. Finally, we will discuss where Nepro with Carb Steady fits into this whole equation and I will be happy to answer all of your questions. OK, lets get started.

48



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



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

Presenter

Presentation Notes

48 patients treated with L-carnitine 20mg/kg 3x/week for 6 months 65 patients treated for 6 months with placebo Assignment by center

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

Presenter

Presentation Notes

The top three studies were conducted without the use of EPO, there results indicate that if a patients hgb level were in the 50th percentile and they were treated with CN the hgb would increase to the 70th percentile. EPO became available in 1989 and so the bottom half of the study are 6 trials using carnitine simultaneously with EPO. 5 of the 6 trials demonstrated a reduction of EPO dose while maintaining Hgb levels with CN use. Thus the patient whose EPO dose is in the 50th percentile, with CN use could drop to the 23rd percentile, per this metaanalysis.

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


Bowden, et al. JREN. 2009:19(4);259–266. 6–1 g pills for 6 months, 160 mg EPA, 100 mg of DHA.

55


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!

effectives of nutritional interventions in...

Documents