Title: Evolving Nutritional Support for Pediatric Acute Renal Failure
1 Evolving Nutritional Support for Pediatric Acute Renal Failure
NJ Maxvold MD
Pediatric Critical Care Division
DeVos Childrens Hospital
Grand Rapids MI
2 Nutrition in Pediatric ARF
Overview of Current Knowledge of Altered Metabolic Balances During Stress /Acute Illness
Substrate / Energy Metabolism
Neuroendocrine Axis
Specific Metabolic Alterations in ARF
3 TSH Profile in Critical IllnessG. Van den Berghe. Frontiers in Neuroendocrinology 23 (2002) 370-391 4 GH Profile in Critical IllnessG. Van den Berghe Frontiers in Neuroendocrinology 23 (2002) 370-391 5 NEA SummaryGreet Van den Berghe. Frontiers in Neuroendocrinology 23 (2002) 370-391
6 Mortality Outcome PredictorsG. Van den Berghe Frontiers in Neuroendocrinology 23 (2002) 370-391 7 Van Den Berghe G et al. Intensive Insulin Therapy in Critically Ill Patients. N Engl J Med 2001 3451359-1367
N 1548 pts
Prospectiverandomizedcontrolled Study
Intensive Insulin Therapy Glu80-110
Conventional Insulin Therapy Glu180-200
Diet 20-30 kcalNP/kg/d 0.13-0.26 g N/kg/d
20-40 of kcalNP Lipids.
8 Van Den Berghe G et al. Intensive Insulin Therapy in Critically Ill Patients. N Engl J Med 2001 3451359-1367 9 Van den Berghe G et al. Crit care Med 2003 31359-366
Glycemic Control 80-110 mg/dl
i Crit Illness
i Polyneuropathy
i Bactermia
i Inflammation
i Anemia
Reduction of Mortality
Insulin Dose
Preventive Effect on ARF
Reduction of Mortality
i Inflammation
10 rGH Therapy in Critical Illness
Finnish ( N170) and MultiNational (N190)
Enrolled gt 5 ICU days rGH 5.3/8.0 mg/d
h Hyperglycemia and Insulin Suppl
h Sepsis and MOF
Improved Nitrogen Balance (Finnish)
rGH Supplementation ghMortality RR 2.4
Takala J et al. Increased Mortality associated with Growth Hormone Treatment in Critically Ill Patients. N Engl J Med 1999341785-92
11 Hypothalamic Secretagogues for Pituitary and Metabolic Improvement
N14 Prolonged Illnessgt 14 ICU days
GHRP-2 TRH for 5 day therapy crossing over to placebo
600 am GHRP-2 bolus 1 mcg/kg and TRH bolus of 1 mcg/kg then
continuous infusion of 1mcg/kg/hr
Restored the pulsatile profile of GH and TSH and peripheral responses (IGF-I IGFBP-3 ALSLeptin Insulin)
No effect of Cortisol levels
Improved Urea to creatinine ratio
Van den Berghe G et al. J Clin Endocrinol Metab 84 1311-1323 1999
12 Neuroendocrine Axis Modulation in Acute Illness
Acker CG et al. A trial of thyroxine in ARF. Kidney Int 200057293-298
Triiodothyronine Suppl (T3)ghMortality
Bettendorf M et al. Lancet 2000 Aug 12 356(9229)529-34
40 Postop Cardiac Children Randomized Blinded
2mcg/kg T3 on Day 1 thereafter 1mcg/kg/d
Improved Cardiac Index
20 (T3) vs 10 (Placebo)
13 Future Nutritional Adaptions
Potential Endocrine Intervention in ARF
Ding H et al. J Clin Invest 1993 912281-7
IGF-1 Accelerate Regeneration in ARF
Improved Nitrogen Balance
Hirschberg R et al. Kidney Int 1999 552423-32
IGF-1 No clinical effect in ARF patients
14 Lipid UtilizationCritical Illness
Fatty Acids
l m
l m
l m
Oxidation ffffngggg Fat Accrual
(Acute) /// (Prolonged)
///
Leptin
15 NEA Leptin
Source Adipocyte pulsatile release
16 -kDa Protein hormone encoded obgene
Actions
Appetite Control (Neuropeptide Y)
Substrate (Fat) Utilization
Bone Metabolism
16 Pediatric Nutrition
Components of Pediatric Nutrition in ARF
1. Growth and Development of Child
2. Cessation anabolic growth during acute
illness
A.Maintenance of Cellular Metabolism
B. Repair / Healing Process
17 Nutrition in ARF
Acute Renal Failure Nutritional Effects
High Protein Catabolic Rate
Altered Amino Acid Profile
Altered Substrate Utilization and Elimination
Altered Renal Solute Clearance and UF
5. Altered Renal Synthetic Function
18 Nutrition in ARF
Protein Support in Acute Renal Failure
Additive Losses by RRT
Nitrogen Balance Can it Occur in ARF
Special AA formulations
Additional Cellular Agonists/Antagonists of Muscle Protein turnover
19 Critical Care Nutrition
Nutritional Components of Critical Illness
Daily Energy Needs/Expenditure
Energy Formulation
Substrate Utilization
Stage of Critical Illness- Neuroendocrine Axis
5. Euglycemic Control
20 Nutrition in Pediatric ARF
Age ( m2) BMR(kcal/m2/hr) REE (kcal/d)
0-1 (.34-.45) 53 320-500
2-6 (.58-.8) 52-47 740-950
7-10 (1.0) 47-42 1130
11-14(m/1.4) 43-42 1440
11-14(f/1.4) 42-39 1310
15-18(m/1.7) 41-40 1760
15-18(f/1.6) 37-35 1370
BMR from Fleisch table of basal met standards
21 Developmental/Age Effect on Energy and Protein Needs (RDA)
Age Wt BMR REE RDA Protein NCalorie
Infant 9 53 500 972 2 1337
Child 30 43 1130 2400 1.2 1416
Adoles 70 40 1760 2700 0.8 1301
Healthy Nitrogen to Calories 1350
Critical Illness Nitrogen to Calories 1150
22 Estimation of Energy Needs
Harris Benedict Equation
Males BEE 66 (13.7 x W(kg)) (5 x H(cm)) (6.8 x A (yr))
Females BEE 655 (9.6 x W(kg)) (1.7 x
H(cm)) (4.7 x A (yr))
23 Energy Requirements in Illness
Stress Factors Relative Contribution on Hypermetabolic Needs
Burns 1.2 2.0 x BEE
Neoplasm 1.1-1.3 x BEE
Multiple Trauma 1.2-1.4 x BEE
Severe Infection/Sepsis 1.2-1.4 x BEE
24 Measurement of REE
Indirect Calorimetry
REE (kcal/d) VO2 (L/min) x 4.3(kcal/L)
VCO2 (L/min) x 1.1 (kcal/L) x 1440
Steady state of activity FiO2 60 or less
minimal leak (Vti Vte)
25 RQ Measurements
Respiratory Quotient (R) VCO2/VO2
Substrate R
Carbohydrate 1.0
Protein 0.8
Fat 0.7
Synthesis of fat gt1.0
26 RQ Measurements
Potential Errors in RQ
Lack of Steady state Acidosis
Hyperventilation g hCO2
CRRT using as anticoagulation Citrate
1 Citrate 2 CO2
27 Estimated vs Measured Energy
Coss-Bu JA et al.Am J Clin Nutr 2001 Nov74(5)664-9
Hypermetabolic as Metabolic Index (REE/EEE) gt 1.1
REE(ave) 0.23 /- 0.10 MJ/kg/d
EEE (ave) 0.19 /- 0.04 MJ/kg/d
Metabolic Index (ave) 1.2
EEE was predicted from Talbot tables of BMR in children
28 Estimated vs Measured Energy
Correlation of REE(pred) to MEE
Briassoulis G et al Crit Care Med 2000 Vol 28(4)p1166-1172
MEE 1000kcal/m2/d
(1019166) without MOSF
860 kcal/m2/d
(862 241) with MOSF
MEE did not differ significantly between disease groups (Sepsis Brain injury Resp Failure Transplant Cardiac Surg)
29 Briassoulis G et al Energy expenditure in critically ill children. Crit Care Med 2000281166-1172 30 Briassoulis G et al Energy expenditure in critically ill children. Crit Care Med 2000281166-1172 31 Briassoulis G et al Energy expenditure in critically ill children. Crit Care Med 2000281166-1172 32 Glucose Metabolism in Critical Illness
Shift of Glycolysis to Pyruvate then cycling back through the liver for Gluconeogenesis Cori Cycle
Decrease Pyruvate entry into TCA cycle
Therefore net energy produced is significantly diminished and continues to feed into a hypermetabolic state of partial glucose oxidation then regeneration of Glucose High Glucose Turnover
33 Glucose Inefficiency in Acute Ilnness
Glycolysis
Glucosegtgtgt 2 Lactate
DG - 47.0 kcal/mol
TCA Complete Oxidation
Glucose 6 O2 a 6 CO2 6 H2O
DG - 686.0 kcal/mol
34 Glucose Metabolism 35 Glucose Utilization
Studies on Glucose Utilization
Coss-Bu JA et al. Am J Clin Nutr 2001 74664-9
Lipogenesis Glucose Intake 8.5mg/kg/min
No Lipogenesis Glucose 6.1mg/kg/min
Sheridan RL et al. JPEN 1998 22212-6
Maximal Glu Oxidation at 5mg/kg/min
Wolfe R et al. Metabolism 1979281031-9
Maximal Glu Oxidation 4mg/kg/min
36 Lipid Metabolism in Critical Illness
Main Oxidative Fuel in Acute Illness
Neuroendocrine Axis stimulates Lipolysis
h FFA ggg Oxidative fuel
h Glycerol ggg Gluconeogenesis
Wiener M et al. Fat metabolism in injury and stress. Crit Care Clin 1987 325-56.
37 Protein Metabolism in Critical Illness
h Muscle Protein Catabolism
Neuroendocrine/ Cytokine Mediators
iMuscle Protein Synthesis Insulin ResistanceNa Electrochemical Pump
Turnover of Free Amino Acid Pool Main substrate for Gluconeogenesis Synthesis APP by Liver
38 Stress Liver Synthetic Changes
Anabolic
Albumin antithrombin
protein C
High Density Lipoproteins
Stress/Acute Phase
Fibrinogen
Ferritin
alpha-1antitrypsinogen
antiproteases
39 McCann UGFinck CM Meguid MM.Metabolic response in injury and critical Illness. In DeitchVincentWindsor (Eds) Sepsis and Multiple Organ Dysfunction. London WB Saunders2002 40 Nutrition in ARF
Altered Metabolic Functions in ARF
I. Loss of Normal Renal Excretion
1. Daily Body Water Balance
2. Solute Clearance Electrolytes Vitamins mineral and trace elements
Ultrafiltrate/water loss is primarily related to solute excretion ( Na K urea) and preservation of Osmolalitypl (275-290)
Free Water Excretion is dependent upon
1. Ascending Loop of Henle reabsorbtion of
NaCl without water
2. Collecting tubules Impermeability to water
(absent ADH)
42 Altered Metabolic Functions in ARF
Solute Clearance in ARF
Impaired GFR leads to ielimination as well as catabolism increasing many of the electrolytes (K PO4Ca) requiring provisional adjustments.
Vitamin Clearance
Water Soluble- Low when RRT is used
Lipid Soluble-Vit ADE
43 Vitamins in Acute Renal Failure
Water Soluble
Vit B1 Def Altered Energy Metabolism
h Lactic Acid Tubular damage
Vit B6 Def Altered Amino acid and lipid
metabolism i function of T
lymphocytes
Folate Def Anemia i DNA synthesis
Vit C Def Limit 200 mg/d as precursor to
Oxalic acid
44 Vitamins in Acute Renal Failure
Fat Soluble
Vit D Def Hypocalcemia
Vit A Excess i renal catabolism of
retinol binding protein
Vit E Def i gt50 plasma and RBC
45 Metabolic Alterations in ARF
Lipid Elimination in ARF
Lipid Alterations Impaired Lipolysis prolonging the elimination of lipid infusions
Elimination half-life is doubled thereby
i Clearance by gt 50
Druml W et al. Lipid metabolism in acute renal failure. Kidney Int 198324(S 16)139-142
46 Lipid Metabolism in ARF
h LDL and VLDL
iCholesterol and HDL-Cholesterol
Impaired Lipolysis
Lipase Activity 50
i Lipoprotein Lipase
i Hepatic Triglyceride Lipase
Druml W et al. Post-heparin lipolytic activity in acute renal failure. Clin Nephrol 198523289-293
47 Metabolic Alterations in ARF
Amino Acids and Peptide Elimination
Clearance of Amino Acids and Peptides by the Kidney is reduced but due to the Increased hepatic utilization of Amino acids for Gluconeogenesis and APPs
Increased overall Amino Acids Clearance
Druml w et al. Elimination of Amino acids in renal failure. Am J Clin Nutr 1994 60418-423
48 Druml W. Amino Acid Metabolism and Amino Acid Supply in Acute Renal Failure. Continuous Arteriovenous Hemofiltration (CAVH). Int Conf on CAVH Aachen1984 pp231-239. 49 Mitch WE Chesney RW. Amino acid metabolism by the kidney. Mineral Electrolyte Metab 9190-202 (1982) 50 Nutrition in Pediatric ARF
Reduced Muscle Resting Membrane Potential Defect Na electrochemical Gradient
60 Amino Acid Effects in ARF
Heyman SN etal. Kidney Int 199140273-9
Gly Ala Tubular protectant ischemic or
nephrotoxic injury
Wakabayashi Y et al. Am J Physiol 1996270F784-9
Arg Preserves renal perfusion
Singer P et al. Clin Nutr 19909(S)23A
Badalamenti S et al. Hepatology 199011379-386
AA Supplementation- h renal perfusion and GFR and diuresis
61 ARF Nutritional Summary
Nutritional Energy Requirement for children with Acute Renal Failure is determined by the underlying critical illness
Recent studies support use of MEE when possible or using the BMR with no to minimal Acuity Factor (1-1.2)
Early implementation of Insulin support to facilitate euglycemia and lipid utilization
62 ARF Nutritional Summary
Carbohydrate load when possible to be lt7mg/kg/min to minimize lipogenesis and further hTrigly
Protein to provide ratio of Nitrogenkcal
1 100-150 plus additional adjustments for dietary loss of the RRT
Amino Acid formulation to include NEAAs
( Gln Tyr Arg) in addition to EAA
63 ARF Nutritional Summary
Nutritional Monitoring to include in the care of Critically Ill Children with ARF
MEE PCR Nitrogen Balance at the start of the RRT and 1-2 week intervals thereafter or if indicated by clinical change in patient
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