ESPEN Congress Vienna 2009

Nutritional implications of renal replacement therapy in ICU

Nutritional support - how much nitrogen?

W. Druml (Austria)

ESPEN 2009 Vienna, August 29, 2009

Wilfred DrumlDivision of Nephrology

Department of Medicine III, Vienna General Hospital

Austria

wilfred.druml@meduniwien.ac.at

Nutritional Implications of Renal Replacement Therapy

How much nitrogen ?

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

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

Amino Acid Elimination during CAVH

Original figure by Peter Kramer 1982

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.

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

Nutritional Considerations in the Treatment of Acute Renal Failure

adapted from Druml W. NDT 1994; 9 (Suppl.4): 219 -23

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)

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

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)

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

Continuos versus Intermittent Treatment: Clinical Results in Acute Renal Failure

Kierdorf H Contrib Nephrol 1991; 93: 1-12

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)

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!

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

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

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

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”

Phenylalanine and Tyrosine Metabolism in Renal Failure

Plasma concentrations of tyrosine after infusion of a phenylalanine containing amino acid solution

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

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

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

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

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 ?

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)

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

ESPEN 2009 Vienna, August 29, 2009

Thank you for your attention !

Wilfred DrumlDivision of Nephrology

Department of Medicine III, Vienna General Hospital

Austria wilfred.druml@meduniwien.ac.at

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)

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

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)

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

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

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

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