Nutrition Management in Renal Disease

Dr. Inge Permadhi MS., SpGK

Kidney functions• Excretory of waste products (urea) and drugs • Regulation to maintain homeostatic balance

from fluids, electrolytes, and organic solutes– 1600 L/d blood filtering 180 L ultrafiltrate 1.5 L/d

urine excreted• Endocrine with diverse metabolic effects :

– 1,25 (OH)2D3 (25 (OH)D2 1,25 (OH)2D3)– Erythropoietin– Renin synthesis (angiotensinogen angiotensin I)

• Metabolism

AA and protein metabolism in the human kidney

The role of kidney in the homeostasis of protein :• Synthesis of NEAA : serine, tyrosine, arginine,

threonine, lysine, taurine, and tryptophane• Degradation :catabolism of low-molecular weight

protein (< 50.000 Dalton) as insulin, C-peptide, GH, leptin etc)

• Filtration and reabsorption : 50 – 70g/d AA filtered 97-98% reabsorbed by the proximal tubules.

• Urinary excretion of AA : urea

Protein turnover

Body protein12 kg

Free AA pool200 – 250g

ProteinDegradation250 – 300g/d

Proteinsynthesis

Dietary Protein1g/kgBW/d

Amino acidOxidation 70-90g/d

Urea

Endogenous AA synthesis

+ 250 g/d

A schematic view of the major system responsible for the maintenance of body protein homeostasis in human

♂ 70kg

~~

HepaticGlycogenolysis

HepaticGluconeogenesis

POSTABSORTIVEGLUCOSE RELEASE

RenalGluconeogenesis

Participation of liver glycogenolysis, liver gluconeogenesis and renal gluconeogenesis In POSTABSORPTIVE glucose release(Gerich JE et al, Crit Care & Shock 2003 vol 6, no 2)

50%

30%

20%

ALANINE GLUTAMINE

ENDOGENOUSGLUCOSE RELEASE

AA and Protein metabolism in renal failureProtein

degradationProtein

synthesis

Endogenous AA synthesisby the kidney

Increased by:

-acidosis/cortisol

-Insulin resistance (?)

-Micro inflammation (?)

Decreased by:

-Resistance tp GH/IGF-1

-Low nutrient intake

-Hemodialysis

-Peritoneal dialysis

-Altered AA metabolism

-Micro inflammation ? = cytokine

Body protein

Free AA pool

Dietaryprotein

Amino acidoxidation

Reduced by:

-anorexiaIncreased by:

-acidosis

KIDNEYFAILURE

metabolicacidosis

oxidation inmuscles

BCAA↓Valine ↓ ↓Leucine ↓Isoleucine ↓

defectivephenylalaninehydroxylation

Tyrosine ↓

Threonine ↓Lysine ↓Serine ↓

decreaseproduction

Tryptophan ↓reduceprotein bindingarginine ↓

Glycine ↑Citruline ↑Cystine ↑Aspartate ↑Methionine ↑Methyl-histidine ↑

Essential AANon-essential AASpecial AA

Mitch WE. Handbook of Nutrition and the Kidney, 2003

**

**

**

**synthesis by renal >>

***

*synthesis by renal <

SKELETAL MUSCLEprotein breakdown(relative) protein synthesisBCAA oxidation (excess AA)Intracellular glutamine levels

Glutamine effluxGlutamine synthesis

Alanine synthesis

LIVERAcute phase protein synthesisAlbumin synthesisAA oxidation (excess AA) Gluconeogenesis from AAsGlutamine reqGlutamine utilizationUrea synthesis

KIDNEYGlutamine reqGlutamine utilizationGluconeogenesis

ALANINE, GLUTAMINE

Urea Ammonium excretion

AA and PROTEIN Metabolism during Renal FailureCatabolic hormones:•Cortisol•Glucagon•Cathecolamines

Changes in Protein and Amino Acid Metabolism

• Protein catabolism especially from skeletal muscle.

• Protein synthesis• Redistribution amino acids from muscle to the

liver.– Hepatic gluconeogenesis and ureagenesis – Hepatic protein synthesis and secretion of acute

phase protein is stimulated.

•Metabolic acidosis : Acidosis causes the elimination of H+ is diminished increase in net protein breakdown increased production of H+

Potential factors in Uremic Insulin Resistance:Accumulation of uremic toxins HyperparathyroidismMetabolic acidosisRelative vitamin D deficiencyAnemia

Carbohydrate intolerance

•Insulin resistance•Insulin secretion•Insulin clearance•Plasma insulin•Insulin sensitivity

LiverGluconeogenesis Glycogenolysis

KidneyGluconeogenesis

Insulinresistance Insulin Dependent Tissue

GlucoseUptake

SkeletalMuscle

GlucoseUptake

GlucoseUptake

Glicolysis

AdiposeTissue Kidney

Insulinresistance

Glucose uptake

Glycolysis

Non Insulin Dependent Tissue

Lactate Alanine

All other tissue such as: brain, kidney, immune tissue, wound tissue, lung

Gluconeogenesis

FutileCycle

Glucose Plasma

Carbohydrate Metabolism during Insulin Resistance

LACTATE

ALANINE,

GLYCEROL

Renal insufficiency may affect the body’s ability to maintain adequate blood sugar levels

Uremic Hypoglycemia

• Renal insufficiency may affect the body’s ability to maintain adequate blood sugar levels

• Uremic carbohydrate intolerance• Poor caloric intake• Impaired hepatic glycogenolysis• Certain medication use• Prolonged insulin action• Impaired conterregulatory response

The effect of parathyroid/vitamin D in glucose intolerance

• Secondary hyperparathyroid is associated with impaired insulin secretion.

• 1,25-OH2D3 deficiency is contributed to the abnormalities in insulin secretion and glucose intolerant

• Total serum calcium levels would be expected to rise with advanced hyperparathyroidism. – Increasing calcium levels can inhibit insulin secretion in

pancreatic – High levels of intracellular calcium inhibit phosphorylase

phosphatase activity, preventing normal dephosphorylation of glycogen synthase and GLUT 4 in response to insulin

• Effect of parathyroid hormone or vitamin D changing in calcium balance and cytosolic calcium in insulin target tissue cells cause them resistant to insulin

Altered carbohydrate metabolism

PERIPHERAL INSULIN RESISTANCE Defects in glucose uptake by dependent

insulin tissue

HYPOGLYCEMIA

Mechanism of hyperlipidemia in Nephrotic syndrome

FFA + Glycerol

TG

VLDLLIVER

capillaries

LPL

VLDL IDL

LDL

intestine

capillaries

Chylomicron

HDL

LPL

Chylomicron remnant

PeripheralCells

Cholesterol

x

HDL

Kidney

(Lipiduria)

Liver

DietBile acid

FFA FFA

/N

*

*

*

FFA + Glycerol

TG

VLDL

LIVER

capillaries

LPL

VLDL IDL LDL

Delayed catabolism of TG rich lipoprotein resulting in increased concentrations of apoB containing triglyceride-rich lipoproteins in VLDL and IDL and reduced levels of HDL

Mechanism of hyperlipidemia in CRF

PeripheralCells

Cholesterol

HDLHDL

Liver

FFA*

Renalabnormality

Chylomicron remnants

VLDL IDL LDL HDL Lp(a)

Nephrotic syndrome -- ↑ ↑↑ ↑↑↑ N -- ↓ ↑↑↑

CRF -- ↑ ↑ ↑ ↓ ↑

Hemodialysis ↑↑ ↑↑ ↑↑ ↓ ↓ ↑↑

CAPD ? ↑ ↑↑ ↑ ↔ ↑↑↑

Transplantation -- ↑ -- ↑ ↔ ↔

Atherogenicity + + +++ +++ Protective ++

CAPD : continuous ambulatory peritoneal dialysis Nutritional Management of Renal Disease, 1997

COMMON LIPOPROTEIN ABNORMALITIES IN RENAL DISEASE

ESPEN GUIDELINES ON ENTERAL NUTRITION:

ADULT RENAL FAILURE (www.espen,org)

Nutritional problems

• Poor appetite (anorexia) due to renal failure and concurrent illness

• Hypercatabolism due to underlying illness such as severe infection/sepsis, burns, or postoperative healing

• Malnutrition, wasting, cachexia.

InflammationNutrient losses during dialysisMetabolic acidemiaComorbidityLow nutrient intake

Anorexia induced byInadequate clearance of anorexigensImpaired gastric emptyingIncreased leptin levelsComorbid illnesses

Superimposed illness leading toAltered gastrointestinal motilityAltered digestive or absorptive processes

Endocrine disorders of uremiaResistance to insulinResistance to IGF-1 and GHHyperparathyroidHyperglucagonemiaHypotestosteronemia

Blood lossOccult GIT bleedingVenipunctureSequestrian in hemodialyzer

Goal of nutrition therapy– To prevent malnutrition at an early stage of

renal disease and/or to maintain an optimal nutritional status

– To manage the metabolic disorders– To control the accumulation of waste products– To prevent cardio-vascular disease by

treating hyperlipidemia– To prevent bone disease by treating vitamin D

deficiencies and hyperparathyroidism– To retard progression of renal dysfunction

Acute renal failureEspen Guidelines, Clinical Nutrition, 2006

Macronutrients Requirements are not so much determined by:– Severity of underlying disease– The type and intensity of extracorporeal renal replacement therapy– Nutritional status – Associated complications (the extent of catabolism)

• Energy : 20 – 30 kcal/kg IBW/d• Carbohydrate : 3-5 (max 7) g/kgBW/d• Fat : 0.8 – 1.2 (max 1.5) g/kgBW/d• Protein (EAA + NEAA) :

– Conservative therapy : 0.6 – 0.8 (max 1.0) g/kgBW/d– Extracorporeal therapy : 1.0 – 1.5 g/kgBW/d– CCRT, in hypercatabolism: up to maximum 1.7g/kgBW/d

CRRT (continuous renal replacement therapies)

Micronutrients and Vitamins Recommendation in ARFEspen Guidelines, Clinical Nutrition 2000

Vitamins• Water soluble vitamins

– Riboflavin, thiamine, pyridoxine (5mg/d predialysis or 10 mg dialysis), B12

– vitamin C < 50 mg• Fat soluble vitamins

– Vitamin A, E, K are not recommended– Low doses of 1,25(OH)2D3 0.25 µg/d or every second day

Minerals• Phosphorus : 5 – 10 mg/kg/d (limiting phosphorus food : dairy

products, egg yolks, meat)• Calcium : <2 – 2.5 g/d including binder load• Iron : supplementation might be necessary in patients on VLPD or

patients with long term vegetarian dietsTrace elements• Routine supplementation with trace elements is not recommended :

zinc, selenium, copper, aluminum.

Chronic renal failureEspen Guidelines, Clinical Nutrition, 2006

• Energy : 35 kcal/kgIBW/d• Fat : < 30% total calories (saturated fat <10%

total cal, cholesterol < 300 mg/d)• Carbohydrate : simple sugars < 10%• Protein:

GFR (ml/min) ESPEN (g/kgBW/d) NKF(g/kgBW/d)25 – 70 0.55 – 0.6* (2/3 HBV) -

<25 0.55 – 0.6 (2/3 HBV) or 0.60 or o.75 (intolerance energy intake)

0.28 + EAA + KA

CONSERVATIVE THERAPY

* Depending of physical activity, lean body mass, age, gender, degree of malnutrition etc

Chronic renal failureEspen Guidelines, Clinical Nutrition, 2006

Phosphate 600-1000 mg/d

Potassium 1500-2000 mg/d

Sodium 1.8-2.5 g/d

Fluid Not limited

MINERAL REQUIREMENT

* Depending of physical activity, lean body mass, age, gender, degree of malnutrition etc

Haemodialysis and CAPD

ESPEN NKF

Protein (g/kgBW/d)

Haemodialysis 1.2 – 1.4 (>50%HBV) 1.2 (>50%HBV)

CAPD 1.2 – 1.5 (>50%HBV) 1.2 – 1.3 (>50%HBV)

Energy (kcal/kgBW/d)

Haemodialysis 35 < 60 yr 35

CAPD < 60 yr 30

Haemodialysis and CAPD

Phosphate (mg/d) 800 – 1000*

Potassium (mg/d) 2000 – 2500*

Sodium (g/d) 1.8 – 2.5*

Fluid (mL) 1000 + urine volume

* Individual requirements may differ in acute condition

Haemodialysis and CAPDFolic acid 1 mg/d

Pyridoxin 10 – 20 mg/d

Vitamin C 3 – 60 mg/d

Vitamin D Should be given according to serum calcium, phosphorus and PTH levels

Zn* 15 m/d

Se* 50 – 70 μg/d

* In depleted patient

Nutritional Recommendation for Nephrotic SyndromeEspen Guidelines, Clinical Nutrition 2000

Nutrition therapy and pathophysiology 2007

• Energy : 35 kcal/kg/day• Protein: 0.8 mg/kgBW/day

– >1.5 mg/kgBW/d ↑ proteinuria(soy and flaxseed based proteins may be beneficial in reducing proteinuria)

– 50 – 60% HBV • Lipid: cholesterol lowering diets

– 25 – 30% of total calories• Saturated diet : < 7%• PUFA : > 10%• MUFA : > 20%• Cholesterol : 200 mg/day• Fiber : 25 – 30g/day

• Sodium : 3 g/d• Fluids : generally not restricted• Vitamin: vitamin D if vitamin D• Minerals : Zn and Fe if proven deficient, Calcium (<2 – 2.5g/d)