1. Nutrition In Pediatric CRRT
Michael Zappitelli, MD, MSc
Nutrition in AKI AND CRRT
McGill University Health Center
Montreal, Quebec, Canada

2. Objectives
Discuss the impact of nutrition in acute kidney injury... and vice versa
Discuss clearance of nutrition and nutrition adjustment in pediatric CRRT.

3. No real prevention/treatment Poorer outcome, increased mortality
Critical Illness X
No real prevention/treatment
Acute Kidney Injury X
Left with:
1) Modifying the negative effects of AKI
2) Providing adequate nutrition
??? Modify outcome???
Poorer outcome, increased mortality

4. Critical Illness Acute Kidney Injury
hormone changes
Acute: increase
Later: decrease
↑ cytokines
Altered substrate utilization
CH2O: ↑hepatic gluconeogenesis
(shift away from glycolysis)
↑lipogenesis
- Inefficient glucose oxidation
- Insulin resistance
- Shift in use of amino acids:
gluconeogenesis + APR’s
MALNUTRITION
Impaired nutrient transport
Inefficient/inadequate supply
Impaired A.a. conversion
↓lipid oxidation
Uremia
Acidosis
Altered Glucose
metab.
Cytokines
Acute Kidney Injury

5. Critical Illness and Nutrition
Adequate nutrition needed for recovery + normal functioning of growing child.
Tissue synthesis and immune function.
Desire to avoid over- and under-feeding.
Underfeeding: increase morbidity, mortality, infection, wound healing, length of ventilation.

6. Critical Illness and Nutrition
Children: high risk of malnutrition.
High basal metabolic rates.
Limited energy reserves.
High (15-30%) baseline poor nutrition.

7. Malnutrition AND AKI Same difficulties/pathophysiology +
Increased difficulty in nutrition provision.
Higher rate of baseline malnutrition/ comorbidities
Metabolic changes of AKI.
Children with AKI – increased risk of malnutrition at PICU discharge.
RRT – increases nutritional losses.

8. Nutrition and AKI Problem: No evidence-based guidelines.
Difficulty to show effect on hard outcomes.
Recommendations based on
Adult studies
Known metabolic alterations with AKI
Nutrition in critically ill children
Measuring nutritional losses by RRT.

9. Critical Illness – Energy needs
Metabolic needs vary according to the injury.
RDA versus predictive equations vs direct measurement (indirect calorimetry).
No single predictive equation shown to accurately estimate REE.
Limitations to indirect calorimetry in critically ill patients.

10. AKI and energy needs
Controversial – AKI per se may not affect energy expenditure.
Affected more by coexisting conditions.
Almost no data on pediatric AKI and energy needs.

11. Indirect calorimetry AND CRRT
IC: measure resting energy expenditure.
Based on: Expired CO2 and O2 (O2 consumption + CO2 production).
Potential problem with CRRT
May affect IC
measurements.
IC may not be
reliable?
HCO3/CO2 fluxes
Hemofilter
Effluent
Dialysis fluid

12. Critical Illness – Energy needs
Controversy: ? RDA ? 25-30% above REE.
Mean REE in literature: 35 to 60 kcal/kg/day ( MJ/kg/day)
Adults: kcal/kg/day – probably need more in children.
Almost no studies in AKI.

13. Carbohydrates Patients become hyperglycemic.
Insulin resistance, ↑hepatic gluconeogenesis.
Stress hormones
Inflammatory mediators and cytokines
Metabolic acidosis
Pre-existing hyperparathyroidism

14. Critical Illness - protein
Protein synthesis AND breakdown are increased: breakdown more increased.
Manifestation: net negative nitrogen balance, skeletal muscle wasting.
Nitrogen balance = Nin – Nout.

15. Critical Illness & AKI - protein
Protein metabolism abnormal:
Reduced renal synthesis of amino acids
Altered amino acid uptake
Factors related to critical illness (elevated stress hormones, increased hepatic gluconeogenesis, relative insulin resistance).

16. AKI and protein
Protein synthesis CAN be increased by providing more amino acids.
Bellomo et al, Int J of Artif Organs, 2002
Scheinkestel et al, Nutrition, 2003
Still very difficult to achieve positive N balance.

17. therapy in critically ill children. Zappitelli et al, submitted
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
CVVHD clearance of amino acids measured on Day 2 and Day 5 N=15
Amino
Acid
Day 2 (n=15) Day 5 (n=9)
K1 CVVHD CVVHD Losses K Renal (n=2) K CVVHD CVVHD Losses K Renal (n=3)
(ml/min/1.73m2) (mcg/kg/d) (ml/min/1.73m2) (ml/min/1.73m2) (mcg/kg/d) (ml/min/1.73m2)
Mean±SD, Median Mean±SD, Median Mean Mean±SD, Median Mean±SD, Median Mean
Tau
Asp
Thr
Ser
Asn
Glu
Gln
Pro
Gly
Ala
Cit
Val
Cys
Met
Ile
Leu
Tyr
Phe
Orn
Lys
His
Arg
104.5±179.0, ±11.1, ±111.2, ±5.4,
335.8±483.7, ±4.1, ±349.8, ±4.4,
31.9±25.0, ±18.5, ±25.1, ±5.9,
29.1±25.6, ±8.6, ±27.7, ±3.3,
37.2±32.1, ±8.1, ±19.8, ±3.4,
9.4±10.6, ±4.0, ±5.0, ±0.7,
19.4±20.1, ±63.7, ±152.9, ±30.7,
38.3±32.7, ±22.2, ±21.9, ±11.2,
28.1±25.7, ±16.1, ±30.2, ±7.1,
26.1±24.6, ±21.2, ±38.8, ±11.5,
25.6±24.3, ±4.5, ±50.4, ±1.1,
24.8±22.0, ±13.4, ±37.3, ±6.9,
27.4±54.5, ±1.2, ±29.9, ±1.1,
18.0±19.9, ±13.5, ±31.1, ±1.8,
29.9±29.8, ±5.7, ±34.7, ±2.7,
22.9±20.9, ±9.2, ±28.8, ±5.2,
22.2±23.3, ±13.5, ±41.3, ±2.7,
23.9±20.8, ±23.1, ±29.7, ±6.2,
8.4±8.7, ±5.0, ±249.7, ±3.4,
7.7±9.0, ±11.1, ±299.5, ±8.9,
13.2±15.8, ±15.9, ±66.3, ±3.8,
15.8±17.1, ±23.4, ±68.6, ±4.8,

18. Combined results of clearance of essential amino acids by CRRT.
Zappitelli et al (submitted) and Maxvold et al, Critical Care, 2000 (n=6).
Grey bars represent amino acid clearance achieved by continuous veno-venous hemofiltration [4] and black bars from continuous veno-venous hemodialysis [45].
K, clearance; Thr, threonine; Glu, glutamic acid; Gln, glutamine; Pro, Proline; Gly, Glycine; Ala, Alanine; Val, Valine; Met, Methionine; Phe, Phenylalanine; Lys, Lysine; His, Histidine; Arg, Arginine. This graph was derived using data from: Crit Care Med : and J Am Soc Nephrol :767A.
Several studies, adult and child: ~ 10-20% intake “lost” through hemofilter.
Both studies: Highest losses with Glutamine/Glutamic acid

19. therapy in critically ill children. Zappitelli et al, submitted
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
Amino Acid serum levels measured on Days 1, 2 and 5
Amino Acid2
CVVHD initiation % low/normal/high3 Day % low/high/normal Day % low/normal/high
Tau
Asp
Thr
Ser
Asn
Glu
Gln
Pro
Gly
Ala
Cit
Val
Cys
Met
Ile
Leu
Tyr
Phe
Orn
Lys
His
Arg
43±96, / 93.3/ ±102, / 86.7/ ±14, / 88.9/ 0
4±3, / 100.0/ ±5, / 93.3/ ±16, / 66.7/ 22.2
100±81, /60.0/ ±54, / 80.0/ ±67, / 88.9/ 11.1
53±26, / 40.0/ ±30, / 46.7/ ±34, / 55.6/ 0
37±21, / 100.0/ ±23, / 93.3/ ±27, / 77.8/ 11.1
57±89, / 86.7/ ±55, / 80.0/ ±146, / 44.4/ 44.4
315±146, / 53.3/ ±167, / 33.3/ ±261, / 55.6/ 11.1
124±66, / 93.3/ ±69, / 100.0/ ±113, / 88.9/ 11.1
200±135, / 66.7/ ±89, / 66.7/ ±100, / 77.8/ 11.1
195±133, / 80.0/ ±149, / 80.0/ ±192, / 77.8/ 11.1
12±7, / 86.7/ ±8, / 80.0/ ±7, / 77.8/ 0
148±58, / 80.0/ ±43, / 93.3/ ±57, / 88.9/ 0
27±25, / 60.0/ ±24, / 60.0/ ±35, / 55.6/ 11.1
32±52, / 80.0/ ±39, / 53.3/ ±16, / 88.9/ 11.1
31±19, / 86.7/ ±22, / 93.3/ ±23, / 88.9/ 11.1
78±34, / 93.3/ ±28, / 100.0/ ±41, / 77.8/ 11.1
57±38, / 73.3/ ±27, / 86.7/ ±27, / 77.8/ 0
92±59, / 73.3/ ±63, / 46.7/ ±45, / 44.4/ 55.6
47±37, / 86.7/ ±41, / 86.7/ ±84, / 77.8/ 11.1
152±65, / 86.7/ ±84, / 66.7/ ±90, / 66.7/ 22.2
76±32, / 80.0/ ±38, / 80.0/ ±36, / 77.8/ 11.1
43±26, / 80.0/ ±56, / 93.3/ ±31, / 88.9/ 0

20. therapy in critically ill children. Zappitelli et al, submitted
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
Protein and energy intake and output at CVVHD1 initiation, Day 2 and Day 5.
CVVHD initiation (N=15) Day 2 (N=15) Day 5 (N=9)
Mean±SD, Median Mean±SD, Median Mean±SD, Median
Protein intake (g/kg/d)
N balance (g/kg/d)
Caloric intake (kcal/kg/d)
Caloric balance (kcal/kg/day)
1.98±1.24, ±1.02, ±0.60, 2.08
NA ±1.60, ±0.19, -0.24
32.6±27.6, ±22.3, ±18.4, 42.7
-0.4±25.4, ±21.7, ±17.7, +10.8
Maxvold et al, Crit Care Med, 2000
Protein intake was 1.5 g/kg/day – Negative nitrogen balance
It’s not easy to achieve a positive nitrogen balance.
Logic: bigger filter, higher Qd or Quf = increased clearance

21. Does increasing protein intake help?
Scheinkestel et al.
1. Nutrition, 2003
In 11 critically ill adults on CRRT, protein intake 2.5 g/kg/day led to a) normal amino acid levels and b) positive nitrogen balance.
2. Nutrition, 2003
50 critically ill adults on CRRT: 1.5 vs 2.0 vs 2.5 g/kg/day.
NB related to protein intake.
NB related to hospital stay
Protein intake 2.5 g/kg/d: improved survival!

22. What are we doing?
Protein and calorie prescription for children and young adults receiving CRRT:
a report from the Prospective Pediatric Continuous Renal Replacement Therapy
Registry group. Zappitelli et al, submitted.
Age (years)
CRRT duration (days)
Diagnostic category Sepsis/Infection
Renal
Respiratory
Cardiac
Hematology Oncology Gastrointestinal/Hepatic
Other
CRRT indication
Electrolyte imbalance
Fluid overload only
Fluid overload and electrolytes
CRRT modality
CVVHD
CVVH
CVVHDF
8.8 ± 6.8 (8.1, 12.8)
10.2±10.7 (7.0, 11.0) days
N (%)
74 (38.1)
29 (15.0)
12 (6.2)
21 (10.8)
35 (18.0)
15 (7.7)
9 (4.6)
31 (15.9)
66 (33.9)
98 (50.3)
94 (48.2)
52 (26.7)
49 (25.1)

23. Daily change in protein prescription during treatment with CRRT.
Protein and calorie prescription for children and young adults receiving CRRT:
a report from the Prospective Pediatric Continuous Renal Replacement Therapy
Registry group. Zappitelli et al, submitted.
Daily change in protein prescription during treatment with CRRT.
Protein intake
(g/kg/day)
Day of CRRT

24. Daily change in caloric prescription during treatment with CRRT.
Protein and calorie prescription for children and young adults receiving CRRT:
a report from the Prospective Pediatric Continuous Renal Replacement Therapy
Registry group. Zappitelli et al, submitted.
Daily change in caloric prescription during treatment with CRRT.
Caloric Intake
(kcal/kg/day)
Day of CRRT

25. Registry group. Zappitelli et al, submitted.
Protein and calorie prescription for children and young adults receiving CRRT:
a report from the Prospective Pediatric Continuous Renal Replacement Therapy
Registry group. Zappitelli et al, submitted.
Characteristics (N)
Protein intake (g/kg/day)
Initial Maximal
Gender
Males (111)
Females (84)
p-value1
Age Group
≤ 1 year (35)
1 to ≤13 years (95)
>13 years (65)
p-value
MODS (155)
No MODS (40)
Survival
Survivors (117)
Non-survivors (78)
CRRT indication
Electrolytes (31)
Fluid overload (66)
Electrolytes and
fluid overload (98)
1.4, 1.0[1.4] , 1.6[1.6]
1.3, 1.0[1.2] , 1.8[1.5]
1.5, 1.8[1.5] , 2.4[2.3]
1.3, 1.0[1.2] , 1.9[1.5]
1.4, 1.0[1.0] , 1.3[1.1] *
1.3, 1.0[1.2] , 1.8[1.5]
1.5, 1.0[0.8] , 1.3[1.7]
1.4, 1.0[1.2] , 1.6[1.5]
1.3, 1.0[1.3] , 1.8[1.7]
1.2, 1.0[0.9] , 1.4[1.1]
1.6, 1.2[1.2] , 1.8[1.8]
1.2, 1.0[1.3] , 1.8[1.6]
All groups:
Maximal protein>initial
Multivariate predictors of
maximal protein intake
Younger age
Higher initial protein Rx
#CRRT days
Protein Rx >2g/kg/day in 40%

26. Critical Illness & AKI - Lipids
h LDL and VLDL
iCholesterol and HDL-Cholesterol
Impaired Lipolysis
Lipase Activity ~50%
i Lipoprotein Lipase
i Hepatic Triglyceride Lipase

27. Critical Illness - Vitamins
Water Soluble
Vit B1 Def Altered Energy Metabolism,
h Lactic Acid, Tubular damage
Vit B6 Def Altered Amino acid and lipid
metabolism
Folate Def Anemia
Vit C Def Limit 200 mg/d as precursor to
Oxalic acid
Potential for losses during CRRT.

28. Critical Illness - Vitamins
Fat Soluble
Vit D Def Hypocalcemia
Vit A Excess i renal catabolism of
retinol binding protein
Vit E Def i >50% plasma and RBC

29. CRRT-Vitamins
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted * *

30. Critical Illness – trace metals
Deficiencies linked to:
Lymphocyte dysfunction
Cardiovascular dysfunction
Platelet activity
Antioxidant function
Wound healing

31. therapy in critically ill children. Zappitelli et al, submitted
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
K1 Day K Day Serum concentrations­­­­­­­­­­­­­­­­­­_____________________
(ml/min/1.73m2) (ml/min/1.73m2) Initiation Day Day Reference range2
Selenium
Copper
Chromium
Zinc
Manganese
Folate
10.1±7.2, ±3.9, ±19, ±24, ±23, to 190 (µg/l)
0.4±0.3, ±0.46, ±21, 87 L ±27, ±27, to 190 (µg/dl)
24.0±10.6, ±7.1, ±1, ±1, ±0.4, to (µg/l)
4.2±4.1, ±2.4, ±44, 53 L ±28, ±38, to 120 (µg/dl)
9.0±12.9, ±121.4, ±16, 4 H ±15, 3 H ±15, 3 H to (µg/l)
29.4±54.9, ±3.2, ±12, ±4, ±2, to 40 (ng/l)
Churchwell et al, NDT, 2007
Critically ill adults receiving CVVHD and CVVHDF
Transmembrane clearances
Much lower clearance of selenium and chromium
Overall, trace metal clearance negligible.

32. Synthesis Nutritional parameter Nutrition modality Energy Protein
Vitamins
Trace elements
Monitoring
Consider
- Early enteral feeding, will often require parenteral nutrition
- Approximately 25% above basal metabolic needs as measured by metabolic cart or estimated with equations.
20 to 25% as carbohydrates (insulin as needed)
30 to 40% lipid formulations (20% lipid emulsions)
40 to 50% protein
- 2 to 3 g/kg/day with AKI
- Increase intake if on CRRT (by 20%)
- Daily recommended intake
Monitor serum folate, water soluble vitamin levels ± replacement
Resting energy expenditure, nitrogen balance, electrolytes, vitamins, trace elements
Glutamine

33. Acknolwedgements Timothy E. Bunchman Norma J. Maxvold
Stuart L. Goldstein