ESPEN Congress Vienna 2009 Nutritional implications of renal replacement therapy in ICU Nutritional support - how much nitrogen? W. Druml (Austria)
Nutritional Implications of Renal Replacement Therapy How much nitrogen? Wilfred Druml Division of Nephrology Department of Medicine III, Vienna General Hospital Austria wilfred.druml@meduniwien.ac.at ESPEN 2009 Vienna, August 29, 2009
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 Contributing Factors 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, mediatorliberation, 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
Amino Acid Elimination during CAVH Original figure by Peter Kramer 1982
Amino Acid Loss and Plasma Concentrations During Continuous Hemodiafiltration Frankenfield 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 continuousvenovenous 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 therapy Scheinkestel 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? Rates of net proten catabolism in septic patients receiving TPN at three rates of protein intake from Shaw JHF et al. Ann Surg 1987; 205: 288-294
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 Protein / Amino Acid - Requirements 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 > 1.5 Macias 1996 CVVH 1.4-1.6 > 1.5 Leblanc 1998 CVVH 1.75+0.8 > 1.5
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 CRRT Scheinkestel 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 How much amino acids / protein? 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. CAVEAT: Any higher will aggravate toxicity and side effects!
An oral glutamine load enhances renal acid secretion and function Welbourne T. et al. Am J clin Nutr 1998; 67: 660-3 Impact of oral glutamine (2g) on renal function
ICU patients on RRT How much amino acids / protein Renal Reserve Capacity! Can - by increasing the amino acid intake - the renal reserve capacity taken advantage of for acceleration of tubular repair? 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 failure Singer 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 / protein? What type of amino acids solution, what protein should be used? NOTE : Not only the quantitiy but also the quality of 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
Impairment of phenylalanine conversion to tyrosine in end-stage renal disease causing tyrosine deficiency 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
Comparison of a conventionally composed uro solution with an adapted nephro solution Amino Acid conventional* adapted** Isoleucine 9.8 5.8 Leucine 15.4 12.8 Lysine 11.2 12.0 Methionine 15.4 2.0 Phenylalanine 15.4 3.5 Threonine 7.0 8.2 Tryptophan 3.5 3.0 Valine 11.2 8.7 Histidine 3.7 9.8 Arginine 7.5 8.2 Tyrosine (as dipeptide) - 3.0 Cysteine - 0.4 Glycine (i.p. as dipeptide) - 6.3 Serine - 7.6 Proline - 3.0 Calculated as g/l, "conventional" corrected for 100 g/l *"uro"-solution according to "safe intake,** Nephrotect,Fresenius
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 APACHE II score > 10 and renal organ failure at some point in ICU stay Survival Parenteral Feeding Study Glutamine PN 14 survivors 23 ARF (p=0.02) Days from start feeding Control PN 4 survivors 24 ARF Griffiths, Jones, Palmer. Nutrition 1997; 13:295-302
ICU patients on RRT What type of amino acids / protein? 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.
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 Patients Metnitz PGH et a Crit Care Med 2002; 30 : 2051-57 Multvariate predictors of death : Results of stepwise logistic regression analysis
Thank you for your attention! Wilfred Druml Division of Nephrology Department of Medicine III, Vienna General Hospital Austria wilfred.druml@meduniwien.ac.at ESPEN 2009 Vienna, August 29, 2009
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. (r 2 = 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 therapy Berg 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 failure Lefebvre 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