”Nutrition in Kidney Disease”

3rd International Conference of

European Renal Nutrition Working Group of ERA-EDTA

T. Alp Ikizler, MD

Vanderbilt University Medical Center

To provide an overview of the relevance of “nutrition”

in kidney disease

To delineate the mechanisms through which wasting

syndrome develops in kidney disease

To outline the available nutritional interventions that

would counteract protein energy wasting and

dysmetabolism of kidney disease

Goals

Rates of Death and CV Events in Patients

According to GFR

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 1 2 3

UnadjustedAdjusted for demographics and

comorbidities

Years Years

NA/EUR HR =1.2

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 1 2 3

Eur/Aus/NZ

(HR=2.8)

Japan (ref)

North America

(HR=4.0)

Eur/Aus/NZ

(HR=2.6)

Japan (ref)

North America

(HR=3.1)

NA/EUR HR =1.4

The death rate of chronic dialysis patients is

unacceptably high

2012: 4-year survival is 48% HD vs 87% Tx

Limited Efficacy of Randomized Clinical Trials

in CKD/ESRD

MDRD; BEACON; IDEAL

HEMO; MPO; EGESTUDY

DCOR; EVOLVE; VITAL; PRIMO

4D; AURORA; SHARP

NHct; TREAT; CREATE; CHOIR

FINEs; FAVORIT

FOSIDIAL;OCTOPUS

Simplified flow schedule of uremia and its complications

Slide courtesy of Peter Stenvinkel

Current Practices and Challenges

The Need for Paradigm Shift

Treat as many patients as possible

Be cost effective

Minimize testing

Minimize costly treatments

Use simple and applicable treatments

Be pragmatic and practical

Use protocols

Minimize variability

Limit Patient involvement

Limit Physician Involvement

Precision Medicine

Three pillars of Precision Medicine

Right patient,

Right medical care (medicine),

Right time.

Precision Medicine Principles

Personalized care based on molecular, immunologic and

functional endotypes of the disease,

Participation of the patient in the decision making process

Taking into account predictive and preventive aspects of

the treatment

Maintenance Dialysis in 21st Century

Three pillars of Precision Medicine

Right patient

All inclusive

Right medical care (medicine)

One size fits all

Right time

Everything based on numbers

Nutrition, Kidney Disease and Precision Medicine

Personalized care based on molecular, immunologic and

functional endotypes of the disease and treatment.

A long continuum – Stage 1 through 5

Considerations for Nutritional Requirements in Kidney Disease

Protein intake

CKD - Progression

ESRD - Protein wasting

Calorie intake

CKD - Obesity; Insulin Resistance

ESRD - Wasting-Obesity Paradox

CKD and ESRD

Na/K/PO4 (HTN; Hyperkalemia; Bone Mineral Disorders)

Metabolic Disorders (Inflammation; Oxidative Stress)

Nutrient Needs of CKD Patients as Defined by

ESPEN Guidelines*

GFR = glomerular filtration rate; HBV = high biological value; EAA = essential amino acids; KA = ketoanalogues. CAPD=Continuous ambulatory peritoneal dialysis.aAdapted to catabolism levels and to individual needs in case of underweight or obesity.bAdjust as necessary for obese patients.

Cano NJ, et al. Clin Nutr. 2009;28(4):401–414.

Condition

Protein

(Essential and Non-essential

Amino Acids)

Macronutrients

Energy

(non-protein calories)

Non-dialysis CKD patients

GFR = 25-70 mL/min 0.55-0.60b (2/3 HBV)

30-40 kcal/kg/da

GFR < 25 mL/min

0.55-0.60 (2/3 HBV)

or

0.28+EAA or EAA+KA

Hemodialysis 1.2-1.4 (>50% HBV) 35 kcal/kg/day

CAPD 1.2-1.5 (>50% HBV) -

Nutrition, Kidney Disease and Precision Medicine

Personalized care based on molecular, immunologic and

functional endotypes of the disease and treatment.

A long continuum – Stage 1 through 5

Biomarkers – Serum Albumin; hsCRP

Hemodialysis patients, USA,47% (MIS)

Hemodialysis patients, • Sweden: 30 to 43% (SGA)• Netherlands: 28% (SGA)

Peritoneal dialysis patients, Brazil,36 to 65% (SGA)

Peritoneal dialysis patients, China• 29 to 44% (SGA)• 60% (MIS)

Peritoneal dialysis patients, Korea,40% (SGA)

PEW is present in 30 to 65% or more of dialysis patients around the world

Adapted from TNT Renal

Nutritional Markers and Outcomes in ESRD

ALBUMIN PREALBUMIN

0 10 20 30 40 50 60

0.0

0.2

0.4

0.6

0.8

1.0

Q1

Q2

Q3

Q4

Months

Su

rviv

al

Dis

trib

uti

on

Fu

nc

tio

n

Alb

* p-value < .0001

Subjective Global Assessment

Malnutrition-Inflammation Score

Nutrition, Kidney Disease and Precision Medicine

Personalized care based on molecular, immunologic and

functional endotypes of the disease and treatment.

A long continuum – Stage 1 through 5

Biomarkers – Serum Albumin; hsCRP

Multiple phenotypes of “Malnutrition”

Macro- &

Micronutrient

deficiency

Loss of Lean

Body Mass Sarcopenic

Obesity

Metabolic

Syndrome

Obesity

• Obesity > 30 BMI

• Insulin Resistance

Overnutrition•Chronic starvation

without inflammation

Undernutrition

Multiple Phenotypes of “The Malnutrition

Syndrome”

Impaired Utilization

• Acute illness with

inflammation

• Chronic illness with

inflammation

Nutrition, Kidney Disease and Precision Medicine

Personalized care based on molecular, immunologic and

functional endotypes of the disease and treatment.

A long continuum – Stage 1 through 5

Biomarkers – Serum Albumin; hsCRP

Multiple phenotypes of “Malnutrition”

Physiological consequences of dialysis - Catabolism

CVD

Frailty

InfectionCo-Morbid Conditions(Diabetes, CVD, Depression)

Dialysis-Associated Catabolism

Metabolic Derangements(Insulin Resistance, Metabolic Acidosis, IGF-1/GH Resistance)

Dietary Nutrient Intake

Loss of Kidney Function Uremic Toxins

Protein-Energy WastingSarcopenia

Inflammation

Etiology and Consequences of Protein Energy Wasting in CKD

Carrero JJ et al on behalf of ISRNM; JREN 2013

Nutrition, Kidney Disease and Precision Medicine

Personalized care based on molecular, immunologic and

functional endotypes of the disease and treatment.

A long continuum – Stage 1 through 5

Biomarkers – Serum Albumin; hsCRP

Multiple phenotypes of “Malnutrition”

Physiological consequences of dialysis - Catabolism

Participation of the patient in the decision making process

Patients’ dietary preference – Access to nutrients

Considering predictive and preventive aspects of the treatment

Likelihood of success – Improved biomarkers

Only 6.5% of the dieticians did biannual dietary

assessment

Up to 62% “estimated” intake

Median number of patients under care of a dietitian

was 100 (IQR 70-130)

Dedicating dietitian time to development of MNT plan

Prioritize work based on clinical importance and evidence

The regulatory, logistical and administrative requirements

should also be considered as applicable

Nutrition Management: Model for Precision

Medicine in the Kidney Disease

Attempts to manage nutritional aspects of kidney disease

to date have been with limited success primarily due to

lack of consideration of basic characteristics of disease

and patient phenotype and logistics.

Further research is necessary to understand the

mechanisms leading to the lack of beneficial effect and

design more novel approaches.

Involvement of patients in this process will be a key

determinant of future accomplishments