0. Nutrition in Acute Kidney Injury
Antonio R. Paraiso, MD, FPCP, FPSN
Medical Specialist IV, NKTI
Asst. Professor, College of Medicine, UERMMMCI

1. Review of Nutritional Requirements
FOSSIL
FUELS
ORGANIC
FUELS
MECHANICAL ENGINE
METABOLIC ENGINE O 2
COMBUSTION
HEAT
KCal
WASTE

2. OXIDATIVE METABOLISM OF ORGANIC FUELS
ENERGY YIELD
LIPID
9.1 kcal/g
PROTEIN
4.0 kcal/g
GLUCOSE
3.75 kcal/g

3. DAILY ENERGY EXPENDITURE
Predictive equations
BEE (Basal Energy Expenditure) kcal/24 hr
Men = 66 + (13.7 x wt) + (5.0 x ht) – (6.7 x Age)
Women = (9.6 x wt) + (1.8 x ht) – (4.7 x age)
REE (Resting Energy Expenditure)
REE = 1.2 x BEE
Simplified computations: kcal/kg ideal body wt depending on activity
Caloric requirements: 70% from carbohydrates & 30% from fats
Protein requirements: 0.8 to 1.2 in normal metabolism, 1.2 to 1.8 in hypercatabolism

4. ENDOGENOUS FUEL STORES
FUEL STORES IN HEALTHY ADULTS
FUEL SOURCE
AMOUNT (KG)
ENERGY YIELD (KCAL)
ADIPOSE TISSUE
15.0
141,000
MUSCLE PROTEIN
6.0
24,000
TOTAL GLYCOGEN
0.09
900
TOTAL KCAL
165,900
Energy stores can last up to 10 days depending of the rate of catabolism.
Carbohydrate stores are limited and daily intake is needed for CNS functions which rely heavily on carbohydrates
In periods of starvation fat and protein (from breakdown of adipose tissue and muscle) become the main sources of calories

5. METABOLIC ALTERATIONS IN AKI
HYPERMETABOLIC STATE
Energy expenditure (EE) being proportional to the amount of stress
Although active solute transport in a functioning kidney is an energy-consuming process, the presence of AKI by itself (in the absence of critical illness) does not seem to affect resting EE (REE)
EE in AKI patients is therefore determined mainly by the underlying condition. Studies in chronic kidney disease yield conflicting results varying between increased, normal, or even decreased REE.

6. METABOLIC ALTERATIONS IN AKI
‘DIABETES OF STRESS'
hyperglycemia and insulin resistance
Hepatic gluconeogenesis (from amino acids and lactate) increases mainly due to the action of catabolic hormones such as glucagon, epinephrine, and cortisol
The normal suppressive action of exogenous glucose and insulin on hepatic gluconeogenesis is decreased
Peripheral glucose utilization in insulin-dependent tissues (muscle and fat) is also decreased

7. METABOLIC ALTERATIONS IN AKI
UNDERLYING CRITICAL ILLNESS
In normal conditions, the kidney plays an important role in glucose homeostasis
The loss of kidney function by itself may contribute to the altered carbohydrate metabolism in AKI

8. METABOLIC ALTERATIONS IN AKI
PROTEIN CATABOLISM AND NET NEGATIVE NITROGEN BALANCE
The increased protein synthesis is unable to compensate for the higher proteolysis
In the acute phase, this catabolic response may be beneficial, providing amino acids for hepatic gluconeogenesis (supplying substrate for vital tissues such as the brain and immune cells) and for synthesis of proteins involved in immune function and in the acute-phase response.

9. METABOLIC ALTERATIONS IN AKI
PROTEIN CATABOLISM AND NET NEGATIVE NITROGEN BALANCE
However, the sustained hypercatabolism in the chronic phase of critical illness results in a substantial loss of lean body mass and in muscle weakness and decreased immune function
Protein catabolic rates may go up to 1.3 and 1.8 g/kg per day
Protein catabolism also accelerates the increases of serum potassium and phosphorus

10. METABOLIC ALTERATIONS IN AKI
ABNORMAL NUTRIENT PROCESSING
The malnutrition of starvation is due deficits in essential nutrients and nutrient intake will correct the malnutrition
The malnutrition in AKI and other critical illnesses is due to a disease-induced abnormal nutrient processing. Nutrient intake alone may not correct the malnutrition. The underlying disease must be addressed

11. METABOLIC ALTERATIONS IN AKI
NUTRIENT TOXICITY
In healthy subjects ,5% of glucose is metabolized to lactate. In critically ill patients, this may rise up to 85%

12. Who Should Get Nutritional Support?
Patients who:
Cannot meet nutrient requirements
Have documented inadequate oral intake
Have unpredictable return of GI function
Need a prolonged period of NPO/bowel rest

13. IF THE GUT IS AVAILABLE, USE IT!!!
NUTRITIONAL SUPPORT
ENTERAL NUTRITION (EN) IS ALWAYS BETTER THAN PARENTERAL NUTRITION (PN)
Meta-analyses comparing EN with PN - no difference in mortality
Lower incidence of infectious complications with EN
may be explained by the higher incidence of hyperglycemia in patients receiving PN
IF THE GUT IS AVAILABLE, USE IT!!!

14. EN –vs- PN OUTCOMES IN CRITICALLY ILL ADULT PATIENTS
Infectious complications
Favors EN
Favors PN
A systematic review of the literature
Gramlich, K et al, Nutrition 2004

15. EN -vs- PN Mortality Gramlich, K et al, Nutrition 2004 Favors EN
Favors PN
Gramlich, K et al, Nutrition 2004

16. NUTRITIONAL SUPPORT IN AKI
EARLY VERSUS LATE EN
Meta-analysis showed reduced infectious complications and length of hospital stay with early EN, but no effect on noninfectious complications or mortality
However, enterally fed critically ill patients often do not meet their nutritional targets, especially in the first days of ICU stay
Adequate early nutrition is easier with the parenteral route
Most of the mortality benefits of PN suggests that PN should be given when EN cannot be initiated within 24 hours of ICU admission

17. The rationale for early EN
Use of the gut stimulates GALT & MALT ➡ resulting in enhanced immune response
Early feeding can trigger gut immunity and thereby improve outcomes
Delay or failure may promote a pro-inflammatory state with ⇧ disease severity & morbidity
McClave, J Clin Gastro, Sept 2002

18. The rationale for early EN
Absence of gut stimulation is associated with gut atrophy
Changes in gut integrity begin w/in 6 hrs
Higher incidence of infection/ sepsis
“Window of opportunity” = 24 – 48 hrs
Zaloga GP. Crit Care Med 1999;27:259
McClave, J Clin Gastro, Sept 2002

19. NUTRITIONAL SUPPORT IN AKI
OPTIMAL AMOUNT OF CALORIES
Overfeeding should be avoided
Hyperglycemia
excess lipid deposition
Azotemia
excess carbon dioxide (CO2) production with difficult weaning from the respirator
infectious complications

20. NUTRITIONAL SUPPORT IN AKI
OPTIMAL AMOUNT OF CALORIES
Although not based on solid evidence, recent recommendations suggest a nonprotein energy supply
25 to 30 kcal/kg per day in men and 20 to 25 kcal/kg per day in women
The proposed proportions of nonprotein energy supply are 60% to 70% of carbohydrate and 30% to 40% of fat

21. NUTRITIONAL SUPPORT IN AKI
OPTIMAL AMOUNT OF CALORIES
Results from two recent trials renewed interest in hypocaloric feeding, combining normal protein with reduced caloric supply
fewer infectious complications and reduced ICU
caloric intake of between 33% and 66% of the target was associated with better survival

22. NUTRITIONAL SUPPORT IN AKI
PROTEIN INTAKE
Goal is to improve protein synthesis and nitrogen balance
Although negative nitrogen balances are associated with the worst outcomes, there are no randomized studies comparing different protein or nitrogen intakes with regard to clinical outcomes in ICU patients
Although the ideal amount is still debated, a protein intake of between 1.2 and 1.6 g/kg per day (0.16 to 0.24 g nitrogen/kg per day) is usually recommended
Because many nonessential amino acids are not readily synthesized or increasingly used in critically ill patients, the combination of essential and nonessential amino acids is supposed to be superior

23. ROLE OF SPECIFIC COMPONENTS
Glutamine
Most abundant amino acid in the body
Important fuel for cells of the immune system
In stress situations, concentrations decrease and it becomes a 'conditionally' essential amino acid
Available guidelines recommend enteral and parenteral supplementation
Antioxidant micronutrients
Micronutrients (vitamins and trace elements) play a key role in metabolism, immune function, and antioxidant processes, AKI patients have increased oxidative stress
They are deficient in critically ill patients and should be supplemented
Selenium, zinc, vitamin E, and vitamin C show promising effects on infectious complications and/or mortality in ICU patients
Recommended vitamin C in AKI varies between 30 to 100 mg

24. ROLE OF SPECIFIC COMPONENTS
Immunonutrients
Nutrients with an immune-modulating effect include: glutamine, arginine, nucleotides, and omega-3 fatty acids
Arginine is a precursor of nitric oxide synthesis and may be detrimental in critically ill patients with an ongoing inflammatory response
Meta-analysis aggregating the results of three RCTs of enteral supplementation of omega-3 fatty acids (fish oil) in patients with acute respiratory distress syndrome demonstrated that enteral formula enriched with fish oils significantly reduces mortality and ventilator days and tended to reduce ICU length of stay. A role for exogenous omega-3 fatty acids in human renal protection is, at this moment, purely speculative.
Cocktails of several immunonutients (containing glutamine, arginine, nucleotides, and omega-3 fatty acids) in critically ill patients showed no difference in clinical outcome with standard EN

25. AKI
Etiology and severity of AKI is diverse Recommendations for nutritional support can at best be described as debatable

26. CATEGORIES OF AKI PRE-RENAL INTRA-RENAL POST-RENAL
Decreased renal perfusion of whatever cause with preserved integrity of the renal parechyma
INTRA-RENAL
Renal parenchymal disease usually post-ischemic or nephrotoxic and is classicall associated with atn
POST-RENAL
Acute obstruction of the urinary tract

27. SEVERITY OF AKI RIFLE CRITERIA (As recommended by the ADQI)
RISK of renal dysfunction
INJURY to the kidney
FAILURE of kidney function
LOSS of function
END stage kidney disease
SEVERITY
OUTCOME

28. RECOMMENDATIONS FOR NUTRITION IN ACUTE KIDNEY INJURY
CONSERVATIVE
(NON-DIALYZED)
DIALYZED
CASES
USUALLY
MILDER
CASES
MORE
SEVERE ?
EN or PN
There are no large
randomized controlled trials (RCTs)
investigating the effect of
nutritional support
versus starvation in AKI

29. RECOMMENDATIONS IN CRRT
The effect of CRRT on EE and protein catabolic rate is probably small and not clinically relevant.
Blood-membrane contact during RRT may induce a protein catabolic effect – debatable nutritional significance
Protein intake: we do not know the metabolic fate of the administered amino acids
may be used for synthesis of 'beneficial' proteins
may be burnt for energy
May join the inflammatory mediator pool
Daily amino acid losses may reach between 10 and 15 g
Extracorporeal losses of lipoproteins are not to be expected
The optimal nutritional support strategy for patients with AKI requiring CRRT remains a matter of controversy.

30. Traditional administration of PN
Infusion from single bottles via Y-connection early in the history of parenteral nutrition

31. KABIVEN: 3 CHAMBER BAG
ALL IN ONE means that all nutrients in a dose needed for 1 day, such as the
amino acid solution, the glucose solution(s) and the lipid emulsion as well as
additions such as electrolytes, trace elements and vitamins are mixed in one
single container. This admixture is administered over 24 hours via one single
connection at a constant rate to the patient.

32. KABIVEN: Advantages of the All in One system
Improved safety
Saving hospital time and money
Improved vein tolerance due to the lipids contained
Optimal peripheral parenteral nutrition
Metabolic advantages
Safe, efficient and well-tolerated
Increased patient convenience and satisfaction
Facilitating home PN (HPN)

33. Kabiven® Characteristics The Kabiven range: Kabiven (central)
1900 kcal to meet total requirements
Kabiven Peripheral
1000 kcal as a supplement
1400 kcal as a supplement or for TPN

34. Kabiven: Characteristics
Amino acids (g)
Nitrogen (g)
Glucose (g)
Lipids (g)
Total energy
(kcal) 68
10.8
200 80
1900
Kabiven (central, 2.0L) – The contents
Kabiven Peripheral (2.0L) – The contents
Osmolarity: 750 mosm/L
Amino acids (g)
Nitrogen (g)
Glucose (g)
Lipids (g)
Total energy
(kcal) 45
7.2
130 68
1400

35. Nutritional support for acute kidney injury Li Y, Tang X, Zhang J, Wu T
Main results
Compared to lower calorie-total parenteral nutrition (TPN), higher calorie-TPN did not improve estimated nitrogen balance, protein catabolic rate, or urea generation rate, but increased serum triglycerides, glucose, insulin need and nutritional fluid administration.
Urea nitrogen appearance was lower in the low nitrogen intake group than in the high nitrogen intake group.
There was no significant difference in death between EAA and general amino acids (GAA) (RR 1.52, 95% CI 0.63 to 3.68). High dose amino acids did not improve cumulative water excretion, furosemide requirement, nitrogen balance or death compared to normal dose amino acids.
Authors' conclusions
There is not enough evidence to support the effectiveness of nutritional support for AKI. Further high quality studies are required to provide reliable evidence of the effect and safety of nutritional support

36. OUR CONCLUSIONS Use the GUT if available!!!
Non-dialyzed AKI: low protein, adequate carbohydrates
Dialyzed AKI: although no strong evidence is available, physiologic arguments favor nutritional support
If PN is to be used, KABIVEN’s all-in-one 3 chamber bag is convenient either for central or peripheral vein administration