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
• Prospective,randomized,controlled 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,
  ALS,Leptin, 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

• Inefficient Glucose Oxidation iMitochondrial
  Metabolism
• 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
  Resistance,Na 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 UG,Finck CM, Meguid MM.Metabolic response
in injury and critical Illness. In
Deitch,Vincent,Windsor (Eds), Sepsis and Multiple
Organ Dysfunction. London WB Saunders,2002
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
• 3. Substrate Elimination- Amino
  acids,peptides (including Insulin), lipids

41
Fluid Balance in ARF

• 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, PO4,Ca) requiring provisional adjustments.
• Vitamin Clearance
• Water Soluble- Low when RRT is used
• Lipid Soluble-Vit A,D,E

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

• Hypercatabolism of Acute Renal Failure
• Accelerated Muscle Protein Breakdown
• Defective Muscle AA /Protein Synthesis
• Hepatic Gluconeogenesis from A Acids
• Glucocorticoid dependent Pathway

51
Nutrition in Pediatric ARF

• Muscle Protein Catabolism
• Insulin Resistance
• Acidosis
• Catabolic Hormones/Mediators
  Glucocorticoids,Catecholamines,
• TNF-a, Interleukins, Proteases

52
Protein Catabolism in ARF

• Adult Studies
• Protein Catabolic Rate 1.4 - 1.7 g/kg/d
• Macias WL, et al. JPEN
  19962056-62
• Chima CS, et al. JASN 1993
  31516-1521
• Pediatric Studies
• Urea Nitrogen Appearance 185- 290mg/kg/d
• Kuttnig M, et al. Child Nephrol Urol
  19911174-78
• Maxvold N, et al. Crit Care Med
  2000281161-1165

53
Protein Catabolic Rate

• Urea Nitrogen Appearance (UNA)
• UNA (UUN x VU) (UFUN VUF)
• ( BUN2 BUN1) x 0.006 x BW (BW2 BW1) x
  BUN2/100
• BUN2 BUN final BW2 BW final
• BUN1 BUN initial BW1 BW initial

54
Nutrition in Pediatric ARF

• Nitrogen Balance in Acute Renal Failure
• Kierdorf H, et al. Nephrol Dial Transplant
  1986172
• Protein Intake Nitrogen Balance
• 0.7 g/kg/d AA -8.1g N/d
• 1.5 g/kg/d AA -3.4g N/d
• 1.7g/kg/d AA -3.2g N/d

55
Nitrogen Balance in ARF

• Bellomo R, et al. Ren Fail 199719111-120
• Protein Intake Nitrogen Balance
• 1.2 g/kg/d AA -5.5g N/d
• 2.5 g/kg/d AA -1.9g N/d
• Patients were on CRRT

56
CRRT Nutritional Effects

• Protein/AA Losses on CRRT
• Davenport A, Roberts N. Crit Care Med
  1989171010
• Prescrip Polyamide HF, Qbld 140ml/min,QUF
  1L/hr
• Nitrogen Loss of 11 the Intake
• Davies S, et al. Crit Care Med 1991191510
• Prescrip AN-69 HF, Qbld 77 ml/min , QD 1L/hr
  or 2L/hr
• Protein Loss of 9-12 of the daily Intake
• Wide Variance in AAINDIntake Loss
• Gln Tyr Loss gt100 the Intake

57
Glutamine Nitrogen Trafficking

• Primary Nitrogen Transporter
• Signals Muscle Catabolism vs Anabolism
• Precursor of purine / pyridimine
• Substrate for Rapidly dividing Cells (Kidney
  tubular cells, enterocytes, immune cells)

58
Nutrition in Pediatric ARF

• Glutamine
• Precursor for Glutathione
• Substrate for Gluconeogenesis
• Intracellular Osmotic Regulator
• Primary Substrate for Ammoniagenesis
• in Kidney and gut

59
Glutamine Metabolism

• Rested State
• Gln pl 500-600 micromol/L
• Gln Ms 15-20 mmol/L

• Catabolic State
• Rapid Fall in Gln pl
• gt30- 50 Muscle Gln Loss
• 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