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ESPEN Congress Vienna 2009
Nutritional implications of renal replacement therapy in ICU
Nutritional support - how much nitrogen?
W. Druml (Austria)
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ESPEN 2009 Vienna, August 29, 2009
Wilfred DrumlDivision of Nephrology
Department of Medicine III, Vienna General Hospital
Austria
Nutritional Implications of Renal Replacement Therapy
How much nitrogen ?
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Catabolism in critical illness: estimation from urea nitrogen appearance and creatinine production during CRRT
Leblanc M et al. Am J Kidney Dis 1998; 32:444-53
Distribution of nPCR in g/kg/day in the 38 patients
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PROTEIN CATABOLISM IN ARF
endocrine factors: insulin resistance, hyperparathyreoidism uremic-toxic factors: "middle molecules“ acidosis: activation of catabolism and AA-oxidation proteases: imbalance of proteases/ anti-proteases
plus extracorporal therapy: substrate losses, mediator-
liberation, blood-membrane-interaction, etc. blood loss
plus underlying disease: sepsis, MODS etc. unspecific effects of an acute - disease state (SIRS) immobilisation
plus nutritional factors: inadequate intake of substrates
Contributing Factors
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Amino Acid Elimination during CAVH
Original figure by Peter Kramer 1982
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Amino Acid Loss and Plasma Concentrations During Continuous
HemodiafiltrationFrankenfield DC et al. JPEN 1993; 17: 551 - 61
Mean losses of individual amino acids in CHD effluent as a function of mean plasma concentrations of each amino acid.
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Continuous renal replacement therapy amino acid, trace metal and folate clearance in critically ill children
Zappittelli M et al. Intensive Care Med 2009; 35: 698
Amino acid clearance and losses incurred by continuous-venovenous hemodialysis (CVVHD)
a Amino acid clearance on Days 2 and 5 of CVVHD b Amino acid losses on Days 2 and 5 of CVVHD
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Nutritional Considerations in the Treatment of Acute Renal Failure
adapted from Druml W. NDT 1994; 9 (Suppl.4): 219 -23
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Impact of increasing parenteral protein loads on amino acid levels and balance in critically ill anuric patients on continuous
renal replacement therapyScheinkestel CD et al. Nutrition 2003; 19:733
Blood levels of the amino acids on each level of protein feeding (1 to 2.5 g · kg−1 · d−1). Levels at 2.5 g · kg−1 · d−1 were
significantly higher than those at all other levels (P = 0.0001)
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Amino Acid / Protein Intake What do we want ?
from Shaw JHF et al. Ann Surg 1987; 205: 288 -294
Rates of net proten catabolism in septic patients receiving TPN at three rates of protein intake
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Impact of increasing parenteral protein loads on amino acid levels and balance
in critically ill anuric patients on continuous renal replacement therapy
Scheinkestel CD et al. Nutrition 2003; 19:733
Average urea level on each feeding regimen (1 to 2.5 g · kg−1 · d−1 of protein input)
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Nutrition in Critically Ill Patients with Acute Renal Failure
Author Year Modality PCR recomm. intake(g/kg b.w./day)
Kierdorf 1991 CVVH 1.5 1.5
Chima 1993 CAVH 1.7+0.7 1.6 - 1.8
Ikizler 1995 HD 1.74+0.6 > 1.5Macias 1996 CVVH 1.4 - 1.6 > 1.5Leblanc 1998 CVVH 1.75+0.8 > 1.5Ganesan 2009 CVVH 1 57+0 4 ?
Protein / Amino Acid - Requirements
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Continuos versus Intermittent Treatment: Clinical Results in Acute Renal Failure
Kierdorf H Contrib Nephrol 1991; 93: 1-12
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Prospective randomized trial to assess caloric and protein needs of critically Ill,
anuric, ventilated patients requiring CRRTScheinkestel CD et al. Nutrition 2003; 19: 909
Nitrogen balance was positively related to protein intake (P = 0.0075) and was more likely to become positive with protein
intakes larger than 2 g · kg−1 · d−1 (P = 0.0001)
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ICU patients on RRT
The general recommendation for amino acid/ protein intake in a critically ill patient is
1.5 g/kg b.w./day The average loss of amino acids during RRT is
about 4 g/h intermittent hemodialysis therapy about 0.2 g/l filtrate / dialysate during CRR
The current recommendation for catabolic ICU patients on RRT is 1.4 – 1.7 g/kg b.w./day(including the compensation of RRT-losses)
There is no obvious reason why patients should receive more that this.
How much amino acids / protein ?
CAVEAT: Any higher will aggravate toxicity and side effects!
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An oral glutamine load enhances renal acid secretion and functionWelbourne T. et al. Am J clin Nutr 1998; 67: 660-3
Impact of oral glutamine (2g) on renal function
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ICU patients on RRT
Can - by increasing the amino acid intake - the renal reserve capacity taken advantage of for acceleration of tubular repair ?
How much amino acids / protein„Renal Reserve Capacity!
NOTE : Certainly not for oliguric patients / subjects on RRT
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High-dose amino acid infusion preserves diuresis and improves nitrogen balance in non-oliguric
acute renal failureSinger Pierre Wien klin Wochenschr 2007; 119: 218-22
Daily variations of creatinine clearance and nitrogen balance in the groups with low (75 g/day) (N = 6) and high (150 g/day)
(N = 8) amino acid intake
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ICU patients on RRT
What type of amino acids solution, what protein should be used ?
What type of amino acids / protein ?
NOTE : Not only the quantitiy but also the qualityof the amino acid solution / protein is important!
“IT´S NOT NITROGEN ONLY”
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Phenylalanine and Tyrosine Metabolism in Renal Failure
Plasma concentrations of tyrosine after infusion of a phenylalanine containing amino acid solution
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Boirie Y et al.Kidney int 2004; 66: 591
Comparison of phenylalanine conversion to tyrosine as a function of phenylalanine flux and phenylalanine concentration and tyrosine/phenylalanine ratio in control and end-stage renal disease (ESRD) subjects.(A) Phenylalanine to tyrosine/phenylalanine flux. (B) Phenylalanine to tyrosine/phenylalanine concentration. (C)Tyrosine/phenylalanine
Impairment of phenylalanine conversion to tyrosine in end-stage renal disease causing tyrosine deficiency
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Comparison of a conventionally composed „uro“ solution with an adapted „nephro“solution
Calculated as g/l, "conventional" corrected for 100 g/l*"uro"-solution according to "safe intake“,**
Nephrotect®,Fresenius
Amino Acid conventional* adapted**Isoleucine 9.8 5.8Leucine 15.4 12.8Lysine 11.2 12.0Methionine 15.4 2.0Phenylalanine 15.4 3.5Threonine 7.0 8.2Tryptophan 3.5 3.0Valine 11.2 8.7Histidine 3.7 9.8Arginine 7.5 8.2Tyrosine (as dipeptide) - 3.0Cysteine - 0.4Glycine (i.p. as dipeptide) - 6.3Serine - 7.6Proline - 3.0
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Influence of a Novel Amino Acid Solution (enriched with the dipetide Glycyl-Tyrosine)
on Plasma Amino Acid Concentration of Patients with ARF
Smolle KH et al. Clin Nutr 1997; 16: 239 - 246
Changes of the serine/ glycine, phenylalanine/ tyrosine and essential/ non-essential amino acid ratios in plasma
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Survival of renal failure patients
Survival
Days from start feeding
APACHE II score > 10 and renal organ failure at some point in ICU stay
4 survivors24 ARF
(p=0.02)
Glutamine PN 14 survivors23 ARF
Control PN
Parenteral Feeding Study
Griffiths, Jones, Palmer. Nutrition 1997; 13:295-302
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ICU patients on RRT
The type of amino acids solution and/ or protein is relevant but for the moment being no sufficient evidence is available to draw a firm conclusion ….
What type of amino acids / protein ?
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Recovery from ischemic ARF is improved with EN compared with PN
Mouser JF et al. Crit Care Med 1997; 25: 1748-54
Creatinine clearance (mean/SD) in rats infused with enteral nutrition (solid bars) or parenteral nutrition (hatched bars).a p < .05)
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Effect of ARF Requiring Renal Replacement Therapy on Outcome in
Critically Ill PatientsMetnitz PGH et a Crit Care Med 2002; 30 : 2051-57
Multvariate predictors of death : Results of stepwise logistic regression analysis
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ESPEN 2009 Vienna, August 29, 2009
Thank you for your attention !
Wilfred DrumlDivision of Nephrology
Department of Medicine III, Vienna General Hospital
Austria [email protected]
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Impact of increasing parenteral protein loads on amino acid levels and balance
in critically ill anuric patients on continuous renal replacement therapy
Scheinkestel CD et al. Nutrition 2003; 19:733
Correlation between blood levels of amino acids and ultrafiltrate levels of amino acids. (r2 = 0.99, P = 0.0001)
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Impact of increasing parenteral protein loads on amino acid levels and balance
in critically ill anuric patients on continuous renal replacement therapy
Scheinkestel CD et al. Nutrition 2003; 19:733
In a multivariate analysis TPN had no effect on patient outcome, but enteral feeding had a significant benefit (P = 0.028)
CL, confidence limits; OR, odds ratio; ROD, risk of death; SMR, standardized mortality ratio
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Glutamine kinetics during intravenous glutamine supplementation in ICU patients on continuous renal replacement therapyBerg A et al. Intensive Care Med 2007; 33: 660-66
Correlation between GLN concentrations (μmol/l) in dialysate fluid and in venous plasma at end of the 20-h infusion of ALA-GLN or placebo in ICU patients on CRRT (net – loss about 3.6 g/ day)
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Amino acid loss and nitrogen balance in critically ill children with acute renal failure:a prospective comparison between classic
hemofiltration and hemofiltration with dialysis
Maxvold NJ et al. Crit Care Med 2000; 28: 1161
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Small bowel motility and colonic transit are altered in dogs with
moderate renal failureLefebvre HP et al. Am J Physiol 2001; 231: R230
Correlation between the total amount of water excreted in feces over 4 days and the colonic transit time (P = 0.004). and ,
values before and after RF
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Amino acid loss and nitrogen balance in critically ill children with acute renal failure:a prospective comparison between classic
hemofiltration and hemofiltration with dialysis
Maxvold NJ et al. Crit Care Med 2000; 28: 1161
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Impact of increasing parenteral protein loads on amino acid levels and balance
in critically ill anuric patients on continuous renal replacement therapy
Scheinkestel CD et al. Nutrition 2003; 19:733
Levels of amino acids in each feeding regimen (1 to 2.5 g · kg−1 · d−1 of protein input). y axis = logarithmic scale, with 100% representing the lower limit of normal. Hatched area =
normal range for each amino acid