Nutrition in Acute Kidney Injury Enrico Fiaccadori

Nutrition in Acute Kidney Injury Enrico Fiaccadori Nephrology Dept. Parma University Medical School Parma, Italy

Diagnosis, epidemiology and prognostic impact of proteinenergy wasting (PEW) in AKI Pathogenetic mechanisms of PEW Nutrient needs and artificial nutrition in AKI: indications from Guidelines Nutrition and outcome in AKI

The ISRNM expert panel recommends the term protein energy wasting for loss of body protein mass and fuel reserves A diagnosis of PEW can be made when at least one parameter is found below recommendation in three of the four nutritional variable groups

A major open problem in AKI is the lack of adequate tools for nutritional status evaluation at the individual level, and for monitoring of the effects of nutritional support Fiaccadori E et al. Curr Op Clin Nutr Metab Care 2013; 16:217-224

Rapid weight changes due to fluid shifts during RRT do not influence US measures Nº Measurements Before After P Assessor 1 231 11.7 (4.0) 11.6 (3.9) 0.0967 Assessor 2 258 11.5 (4.6) 11.4 (4.5) 0.2544 Mean (SD), data in mm. Patients with weight loss during RRT (range 0.5 3 Kg in 4 to 10 hours HD or SLED) Sabatino A et al., Clin Nutr 2017; 36:1710

Protein energy wasting is common in AKI Distribution of AKI patients among SGA classes Prevalence of malnutrition in acute kidney injury (n = 674, 1994-2001) SGA B (177/674) SGA A: normal nutritional status SGA A (281/674) 40% 25% SGA B: at risk of malnutrition SGA C: severe malnutrition SGA C (249/674) 35% Nutritional status evaluation by the SGA method (Subjective Global Assessment of nutritional status, Baker JP et al., NEJM 1982; 306:969-72) Rotelli C et al, Intensive Care Med 2001; 27:S189

PEW is associated with increased mortality risk in AKI In-hospital mortality according to nutritional status in 309 ICU pts with AKI A B C Nutritional status by SGA (Subjective Global Assessment of nutritional status, Baker JP et al., NEJM 1982; 306:969-72) Malnutrition is an independent risk factor for mortality in patients with AKI Fiaccadori E et al., J Am Soc Nephrol 1999; 10:581-593

Pathogenesis of PEW in AKI Fiaccadori E et al. Curr Op Clin Nutr Metab Care 2013; 16:217-224

The concept of energy debt in critically ill patients kcal 2000 1800 1600 1400 1200 1000 800 600 400 200 0 Energy Debt 1 3 5 7 9 11 13 15 17 19 21 Days Prescribed Engergy Energy Received From Enteral Feed High energy debts in ICU are associated with: ICU LOS Days on MV Complications Mortality Rubinson L et al., CCM 2004; 32:350-357 Villet S et al., Clin Nutr 2005; 24:502-509 Dvir D et al., Clin Nutr 2006; 25:37-44 Petros S et al., Clin Nutr 2006; 25:51-59

Secondary analysis in 1456 patients with AKI on CRRT in the RENAL Trial Overall mean calorie delivery 867 Kcal/day (10.9 Kcal/Kg/day) Overall mean protein delivery 34.8 g/protein/day

No advantages on N balance in AKI with high calorie intakes 10 30 Kcal/Kg 40 Kcal/Kg Nitrogen balance g/24 hours 0-10 -20-30 Isonitrogenous nutritional support (proteins 1.5 g/kg/day) Baseline Pre TNA Reg. 1 Reg. TNA 22 Study periods Reg. 1: - 30 Kcal/Kg - 0.25 g N/Kg - n.p. Kcal/N ratio 119 Reg. 2: - 40 Kcal/Kg - 0.25 g /Kg - n.p. Kcal/N ratio 159 Fiaccadori E et al., Nephrol Dial Transpl 2005, 20:1976-80

Problems with high calorie regimens in AKI patients Increased fluid administration Increased insulin needs Higher serum glucose levels Fiaccadori E et al., Nephrol Dial Transpl 2005, 20:1976-80

Survival curve of 28-day mortality by the presence or absence of fluid overload (FO) in the patients with AKI in the ICU A positive fluid balance is associated with a worse outcome in patients with AKI

Unintentional overfeeding in AKI Fiaccadori E et al. Curr Op Clin Nutr Metab Care 2013; 16:217-224

Total body water is often increased in AKI actual BW not always the right reference base for nutrient intake calculations

Five different body weights (BW) in patients with AKI in the ICU Usual BW Ideal BW BW at ICU admission BW at nutritional support planning Dry BW during RRT

Two different patients in the same person Fluid overload Nutritional status? Dry body weight Severe malnutrition!

Gentleman Mask, Carnival of Venice, Italy In ICU patients (and in particular in patients with AKI) severe protein-energy wasting can be, at least in part, masked by severe fluid overload

Unintentional overfeeding in AKI Fiaccadori E et al. Curr Op Clin Nutr Metab Care 2013; 16:217-224

Citrate is increasingly utilized, with excellent results, for regional anticoagulation of the circuit in RRT - Citrate is a key energy substrate for cells - Citrate is metabolized in the Krebs cycle - 5 mmoles of citrate (1 gr) correspond to 3 Kcal - Citrate load to the patient during RRT with citrate is highly - variable citrate as a potential, hidden calorie source Clin J Am Soc Nephrol 2014; 9:2173-2188

Not all the RRTs in the ICU are the same: citrate load in CVVH Assuming postdilution, a blood flow of 200 ml/minute, a citrate infusion rate of 3 mmol/l blood flow (36 mmol/hour), a filtration fraction of 0.20, and a filter running 80% of the time, about 553 mmoles of citrate enter the patient s circulation per day, providing close to 333 kcal/day Oudemans-van Straaten HM et al, Critical Care 2011; 15:2020

2012 CVVHDF with ACD-A and lactate-buffered replacement/dialysis fluid ACD-A Average 24 hour calorie load (from lactate, citrate and glucose) up to 1200 Kcal/day Citrate 113 mmol/l in 2.5% dextrose Dialysis fluid with lactate as a buffer

807 SLED sessions (8-12 hours) in 116 pts with AKI in the ICU ACD-A at 300 ml/hour in the circuit, blood flow 200 ml/min, dialysis fluid at 300 ml/min Citrate load in the circuit 34 mmol/h Citrate removal by dialysis 65% Citrate load to the patient 12 mmol/h x 8 hours 96-144 mmoles/sled session Kcal from citrate 60-90 Kcal/SLED (not more than 200 Kcal including glucose) Clin J Am Soc Nephrol 2013; 8:1670-1678

Measured energy needs in AKI REE, Kcal/24 hours REE in critically ill patients with AKI 1835 Kcal/69 Kg = 27 Kcal/Kg/day Faisy C et al., Am J Clin Nutr 2003; 78:241-9

Protein catabolic rate (PCR) in critically ill patients with AKI on different RRT modalities 2 Protein catabolic rate (npcr), g/kg/day 1,5 1 0,5 Chima 1993 (CAVH) Macias 1996 (CVVH) Leblanc 1998 (CVVH) Marshall 2002 (SLED) Fiaccadori 2005 (SLED or IHD) 0 PCR 1.5 g/kg/day in a 75 Kg patient = 3 Kg of lean body mass lost per week Chima CS et al, J Am Soc Nephrol 1993; 3:1516 Macias WL et al, J Parent Ent Nutr 1996; 20:56 Leblanc M et al, Am J Kidney Dis 1998; 32:444 Marshall MR et al, Am J Kidney Dis 2002; 39:556 Fiaccadori E et al., Nephrol Dial Transpl 2005; 20:1976

GUIDELINES AKI NOT ON RRT AKI ON RRT Kcal/Kg Kcal/Kg Glycemic control range recommendations Energy needs in AKI: indications from Guidelines ESPEN 2006-2009 Clin Nutr 2006; 25: 295-310; Clin Nutr 2009; 28: 401-414 ASPEN 2010 JPEN 2010; 34: 366-377 KDIGO 2012 Kidney Int 2012; 29 (suppl): 1-138 20-30 (non-protein calories) 20-30 (non-protein calories) 20-30 (total calories) 20-30* (nonprotein calories) 20-30 (nonprotein calories) 20-30 (total calories) Not mentioned Not mentioned 110-149 mg/dl KDOQI on KDIGO 2012 AJKD 2013; 61: 649-672. 20-30 (total calories) 20-30 (total calories) 110-149 mg/dl Canad. Soc. Nephrol. on KDIGO 2012 AJKD 2013; 61: 673-685 Not mentioned Not mentioned Not mentioned EBPG on KDIGO 2012 NDT 2012; 27: 4263-4272 20-30 (total calories) 20-30 (total calories) 110-180 mg/dl

GUIDELINES AKI NOT ON RRT AKI ON RRT Protein g/kg Protein g/kg Protein needs in AKI: indications from Guidelines ESPEN 2006-2009 Clin Nutr 2006; 25: 295-310; Clin Nutr 2009; 28: 401-414 ASPEN 2010 JPEN 2010; 34: 366-377 0.8-1.0 EAA+NEAA NA 1.0-1.5 (up to 1.7 if CRRT) EAA+NEAA 1.5 (up to 2.5 if CRRT) KDIGO 2012 Kidney Int 2012; 29 (suppl): 1-138 0.8-1.0 1.0-1.5 (up to 1.7 if CRRT) KDOQI on KDIGO 2012 AJKD 2013; 61: 649-672. 0.8-1.0 1.0-1.5 (up to 1.7 if CRRT) Canad. Soc. Nephrol. on KDIGO 2012 AJKD 2013; 61: 673-685 Not mentioned Not mentioned EBPG on KDIGO 2012 NDT 2012; 27: 4263-4272 KDIGO 2012 recommendations for protein intake not endorsed KDIGO 2012 recommendations for protein intake not endorsed

Lipids are an important energy source in AKI Glucose oxidation rate is reduced and fat oxidation rate is increased in AKI

No negative effects of lipid emulsions (MCT/LCT) on filter/extracorporeal circuit life in in AKI Hours of treatment 10 273 SLED in 37 ICU patients with AKI 8 Prescribed duration 8 hours/treatment 6 4 2 n = 130 n = 143 PN with MCT/LCT PN without lipids or on EN Renal ICU Parma University Hospital, unpublished data PN with all-in-one Nutrispecial system 20% MCT/LCT 250-500 ml/day, administered in 24 hours 0

Guidelines recommendations on glycemic control in critically ill patients in the ICU and in patients with AKI

Nutritional support and outcome in AKI No good data from the old ( 80) studies Confusing messages from recent studies

Old studies ( 80) on nutrition and outcome in AKI: methodological problems Few patients Suboptimal selection of patients Population and syndrome heterogeneity No stratification for severity of illness No stratification for nutritional status Use of historical controls or no controls at all In most cases retrospective studies Quantitative inadequacy of Kcal and/or N intake Qualititative inadequacy of Kcal and/or N intake Inadequate duration of nutritional support

*DCI: delivery of caloric intake

Mean calorie delivery in survivors vs non-survivors: 847 vs 883 Kcal/day (10.4 vs 11.2 Kcal/Kg/day) Mean protein intake: 33.6 g/kg/day vs 35.7

- An increase of 1000 Kcal was associated with reduced 60-day mortality (OR 0.61; 95% CI 0.48-0.77, P < 0.001) and more ventilator-free days (2.8 days, 95% CI 0.53-5.08, P = 0.02) - - An increase of 30 g protein/day was associated with reduced 60-day mortality (OR 0.61; 95% CI 0.48-0.77, P < 0.001) and more ventilator-free days (1.92 days, 95% CI 0.58-3.27)

We have to find the right position for the patients on the dose-response curve of feeding in the ICU survival underfeeding optimal feeding overfeeding Minimal dose of nutrients dose of nutrients

Comparison between measured, estimated, prescribed and delivered calories (130 measurements in 42 pts with AKI)

Decision tree for nutritional support in AKI patients with PEW or at risk of PEW Normal GI tract function? YES NO Parenteral feeding Enteral feeding Are nutritional goals achieved? YES NO Integration with parenteral feeding Peripheral (short-term, with or without fluid restriction Central (long-term, fluid restriction, catabolism) ESPEN Guidelines 2006 & 2009

Enteral nutrition as the first choice for starting nutritional support in the ICU ESPEN Guidelines ASPEN/SCCM Guidelines CSCN Guidelines KDIGO

Enteral nutrition is safe in AKI patients, and should be the first choice, however suboptimal intakes of proteins frequently observed due to the composition of the currently available enteral diets

Artificial nutrition by enteral nutrition beneficial in AKI Metnitz PGH et al., Crit Care Med 2002; 30:2051

Summary a) Patients with AKI are at high risk for Protein-Energy Wasting, an independent predictor of mortality/morbidity in this clinical setting b) Energy (non-protein) at not more than 25 Kcal/Kg/day should be provided in critically ill patients with AKI; prudential protein intake in patients on RRT is up to 1.5-1.7 g/kg/day c) Enteral nutrition should be the initial modality for artificial nutrition in AKI d) At the present time no definitive demonstration from RCTs is available concerning the positive effects of artificial nutrition on prognosis in AKI patients; however, given the high risk for PEW in AKI, artificial nutrition should be considered a key component of therapeutic strategy of the syndrome e) We need more (and better) data