Artificial Nutritional Support in Chronic Hemodialysis Patients: A Narrative Review

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1 REVIEW Artificial Nutritional Support in Chronic Hemodialysis Patients: A Narrative Review Maurizio Bossola, MD,* Luigi Tazza, MD,* Stefania Giungi, MD,* Fausto Rosa, MD, and Giovanna Luciani, MD* Objective: Malnutrition is common in hemodialysis (HD) patients and is a powerful predictor of morbidity and mortality. While much progress has been made in identifying the causes and pathogenesis of malnutrition in patients on HD, no consensus has been reached on its management. Nutritional counseling, appetite stimulants, growth hormone, androgenic anabolic steroids, and anti-inflammatory drugs have been tested with contradictory and nonconclusive results. Oral nutritional supplements (Ss) and intradialytic parenteral nutrition (IDPN) also have been studied. Design/Setting/Patients: We searched the MEDLINE and PubMed databases for randomized clinical trials, comparative nonrandomized clinical trials, studies with patients who were controls for themselves, and singlearm studies on S and IDPN. Thirty-four studies (3223 patients) have been identified and analyzed. Seventeen studies were on S (778 patients) and 17 were on IDPN (2475 patients). Results: S may improve serum albumin levels and/or other nutritional parameters, whereas there are insufficient data on clinical outcome. IDPN improves serum albumin and body weight. Conclusion: Data on survival are conflicting but the only study with an adequate population sample shows that IDPN does not influence survival. Randomized, controlled studies are needed to clarify the role of S and IDPN in the treatment of malnutrition in HD. Ó 2010 by the National Kidney Foundation, Inc. All rights reserved. *Hemodialysis Service, Department of Surgery, Catholic University, Rome, Italy. Department of Surgery, Catholic University, Rome, Italy. Address reprint requests to Maurizio Bossola, MD, Istituto di Clinica Chirurgica, Università Cattolica del Sacro Cuore, Largo A.Gemelli, Roma, Italia. maubosso@tin.it Ó 2010 by the National Kidney Foundation, Inc. All rights reserved /$36.00 doi: /j.jrn MALNUTRITI is common in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD) with prevalence in predialysis ranging from 20% to 80%. 1 4 After initiation of dialysis, the nutritional status tends to improve significantly. 4,5 However, malnutrition remains common among patients receiving dialysis, with the prevalence varying between 23% and 73%. 1 5 The pathogenesis of malnutrition in patients on HD is multifactorial and secondary essentially to predialysis restrictive diets, inadequate nutritional intake due to anorexia, gastropathy and enteropathy, inflammation and/or infection, medications, psychosocial factors (depression, poverty, alcohol/ drugs abuse), dialysis-related factors (inadequate Kt/V, postdialysis fatigue, cardiovascular instability), dialysis-related nutrient losses, alterations in protein metabolism, metabolic acidosis, and inflammation. 1 5 Malnutrition increases morbidity and mortality and significantly affects quality of life. In recent years, much progress has been made in identifying the causes and the pathogenesis of malnutrition in patients on HD as well as in recognizing the link among malnutrition, inflammation, and mortality. 6 However, malnutrition remains a frustrating condition for the clinicians, with the therapeutic armamentarium being poor and not extensively applied in the clinical practice. Along with conventional interventions such as nutritional counseling, novel preventive and therapeutic strategies have been tested, such as appetite stimulants, growth hormone, androgenic anabolic steroids, and anti-inflammatory drugs with contradictory and nonconclusive results. 6 Oral nutritional Journal of Renal Nutrition, Vol 20, No 4 (July), 2010: pp

2 214 BOSSOLA ET AL supplements (S) and intradialytic parenteral nutrition (IDPN) also have been studied as a strategy to prevent and/or treat malnutrition in chronic patients on HD. 6 The aim of the present review is to evaluate the safety and efficacy of S and IDPN in preventing and treating malnutrition in chronic patients on HD. Methods We searched the MEDLINE and PubMed databases (from January 1990 through July 2009) for randomized clinical trials (RCT), comparative non-randomized studies (CNRS) and studies with patients who were controls for themselves (CS) of S, IDPN, and enteral nutrition. We searched the MEDLINE and PubMed using combinations of the following keywords: hemodialysis and oral nutritional supplements, hemodialysis and S, hemodialysis and oral dietary supplements, hemodialysis and nutrient, intradialytic parenteral nutrition, IDPN, hemodiaysis and energy-protein, and hemodialysis and oral protein supplements. We included only human studies. We also examined the reference lists of articles identified by this search strategy and selected those we judged relevant according to the above criteria. Finally, we searched MEDLINE using the acronyms or full titles of the major trials and cohort studies to identify additional publications (Fig. 1). Overall, 34 studies with a total of 3223 patients have been identified and analyzed. Seventeen studies were on S (778 patients) and 17 were on IDPN (2475 patients). Oral Nutritional Supplements S specific for HD patients have been designed to provide adequate energy, protein, Key words ORAL NUTRITIAL SUPPLEMENTS ORAL DIETARY SUPPLEMENTS NUTRIENTS SUPPLEMENTS IDPN REFERENCE LISTS MEDLINE FOR TRIALS REVIEW = 16 REVIEW = 16 REVIEW = 13 REVIEW = VITAMINS, IR, CALCIUM, OTHERS = VITAMINS, IR, CALCIUM, OTHERS = VITAMINS, IR, CALCIUM, OTHERS = NUTRIENTS = 18 IDPN = 12 IDPN = 12 IDPN = NUTRITINAL ASSESSMENT = 16 NUTRITINAL ASSESSMENT = 18 NUTRITI0NAL ASSESSMENT = 3 NUTRITIAL ASSESSMENT = Fouque Steiber Caglar Wilson 2 Patel Ewers 4 Sharma Scott Eustave Mastroiacovo 18 Pupim, Snuder, Shuman, Hiroshige, Mortelmans, Berneis, Krause, Cherry, Czekasky, Orellana, Joannidis, Dezfuli, Cano Capelli, Fouks, Chertow 6 Cuppari Beutler Acchiardo Shah Kuhlmann Cockram Figure 1. Flow diagram showing how studies were accumulated from PubMed and MEDLINE search.

3 ARTIFICIAL NUTRITI IN HEMODIALYSIS 215 vitamins and minerals, and limited amounts of potassium, phosphate, and fluids. They are available as energy or protein sources or a combination of both. Supplements are in the form of solid food, powders, or liquid formulations. Overall, four RCT have been conducted (Table 1). Some of these studies included less than 10 or 20 subjects with the probability that the risk factor balance across exposure arms being quite low, thereby negating much of the value of randomization. More than 10 years ago, Kuhlmann et al. 7 randomized 8 malnourished patients to receive, in addition to usual diet, S to increase intake by 25% or by 10% for 3 months. In the first group, a significant increase of serum albumin was observed. Cockram et al. 8 compared the safety and tolerance of three medical nutritional products when used as sole sources of nutrition in 79 stable normally nourished patients on HD. During the first week of the study, baseline medical history and physical examination, gastrointestinal symptom, urea kinetic, bowel habit, and biochemical data were collected while participants ingested their usual diet. During the last 2 weeks, the same data were collected while participants orally ingested 35 kcal/kg actual weight/d of one of three medical nutritional products (one standard formula and two different disease-specific formulae). All three groups achieved a mean energy and protein intake of approximately 35 kcal/kg/d and 1.25 g protein/kg/d during the last 10 days of the sole source feeding period. By intention-to-treat analysis, there were no changes in number or severity of gastrointestinal symptoms, stool frequency or stool consistency, or urea kinetics between the baseline week and during product consumption. In comparison to the standard product, the disease-specific formulations resulted in improved serum phosphorus and calcium-phosphorus product. In the study of Sharma et al., 9 nondiabetic adult patients on HD with a body mass index,20 and a serum albumin,4.0 g/dl were randomized into a control group, who received appropriate monitoring including dietary recall and counseling for the prescribed diet (protein intake of 1.2 g/kg/d and energy intake of 35 to 40 kcal/ kg/d), and two treatment groups who in addition received a post-hd nutritional supplement providing 500 kcal and 15 g of protein (one homemade and one disease specific) for 30 days. All groups showed an improvement in dry weight and body mass index, whereas in the supplemented groups, a significant increase in serum albumin levels and functional scoring on a 10-point Karnoksky scale (from 8.0 to 8.4 versus 8.1 to 8.0) was documented. Fouque et al. 10 assigned 86 patients on HD to standard care or to S for 3 months. Intention-totreat analysis did not show statistically significant changes in dietary intakes as well as in serum albumin and prealbumin levels between groups. However, the supplemented group exhibited an improvement of Subjective Global Assessment score and quality of life. As shown in Table 2, NCRS and CS also have been conducted to explore the role of S in HD-related malnutrition. Cuppari et al. studied 10 patients on HD before and after 3 months of S and showed a significant increase in weight (11.5 kg; 3%) and fat mass but not in muscle mass. 11 Beutler et al. 12 assigned to nutrition supplement and counseling or only to nutrition counseling 11 chronic HD patients for 4 months. Serum albumin levels improved significantly from to mg/dl in the supplemented group and remained unchanged in the comparative group. Shah et al. 13 compared 44 patients on HD who received usual diet with 44 patients on HD who were given usual diet and a nutritional supplement (Nepro; 1 can each day of dialysis for 3 months). There was no significant difference in change in Kidney Disease Quality of Life Questionnaire scores between the two groups, although the physical domain increased significantly in the intervention group. In the study of Patel et al., patients on HD with both a low protein catabolic rate and a dietary protein intake lower than 1.2 g/kg body weight/d received dietary supplements for 2 month. With respect to baseline, an increase of the protein catabolic rate and the total protein intake was observed at month 2 and at 6 months following intervention. Conversely, no significant changes of nutritional status were observed. Wilson et al. 15 demonstrated that nutritional repletion occurred more quickly and was maintained for a longer period of time in patients on HD with mild hypoalbuminemia who received the diet counseling associated with oral, with respect to patients who received the diet counseling only. Caglar et al. 16 followed 85 patients on HD for a 3-month baseline period during which they received conventional nutritional counseling. Then, patients were given S specifically formulated

4 216 Table 1. Effects of Oral Nutritional Supplements in Patients on Dialysis: Randomized, Controlled Trials Author No. of Patients Type of Study Duration (mo) Type of Oral Supplementation Energy/Protein intake Effects Kuhlmann et al., 8 HD Randomized controlled Cockram et al., 79 HD Randomized controlled Sharma et al., 40 HD Randomized controlled Fouque et al., 88 HD Randomized controlled 3 1) disease specific supplements to increase intake by 25% 2) disease specific supplements to increase intake by 10% 0.5 1) standard energy and protein 2) disease-specific energy and protein 3) disease-specific energy and protein 1 1) control group: usual diet 1 dietary counseling 2) treatment group: disease specific supplements 1 dietary counseling 3) treatment group: homemade supplement 1 dietary counseling 3 1) control: usual diet 2) renal specific energy and protein Unknown 1) 475 kcal 2) 475 kcal 3) 475 kcal 1) kcal/kg BW/d g protein/kg BW/d 2) 500 kcal 3) 497 kcal 1) standard diet 2) standard diet 1 S (500 kcal g/d) Increase of serum albumin levels Use of enteral nutrition as a sole source of nutrition is both possible and well tolerated in hemodialyzed patients. In both groups, improvement in dry weight and BMI; serum albumin increase with S (from 3.4 to 3.9 g/dl) but not in control group (from 3.4 to 3.5 g/dl) No significant changes in BMI, dry body weight, serum albumin, prealbumin, and C-reactive protein levels; SGA increase of median score with S (from 4 to 6) and decrease without S (from 5 to 4) BOSSOLA ET AL HD, hemodialysis patients.

5 Table 2. Effects of Oral Nutritional Supplements in Patients on Hemodialysis: Nonrandomised Controlled Trials and Cross-over Trials Author No. of Patients Type of Study Duration (mo) Type of Oral Supplementation Energy/Protein Intake Effects Cuppari et al., Patients were controls for themselves Beutler et al., Nonrandomized comparative Shah et al., Nonrandomized comparative Patel et al., Patients were controls for themselves Wilson et al., Nonrandomized comparative Caglar et al., Patients were controls for themselves Acchiardo and 108 Nonrandomized Riley, comparative Steiber et al, Nonrandomized comparative Ewers et al., Patients were controls for themselves Scott et al., Nonrandomized comparative 4 Energy and protein 1.2 /kg Increase of body weight (11.5 kg, 13%) kcal/d Increase of serum albumin with S (from to ; P,.01) and decrease without S (from to ) 3 Energy and protein 475 kcal/d/16.6 g/d Improvement of serum albumin levels; no change in QOL 6 Energy and protein 1.2 g/kg BW/d No change in nutritional status 4 Energy and protein Nutritional repletion more rapid in the experimental group 6 Energy and protein 475 kcal/d/16.6 g/d Increase of serum albumin (from to g/dl; P,.01), prealbumin (from to mg/dl; p,0.01), SGA (from to ; P,.01) Not stated Energy and protein 3 Energy and protein 1.5 Oral unsaturated fat supplement 1 fish oil 4 g 3 Energy (54 g/ glucose/wk) and protein (57 g/wk) 300 kcal/d g/d With S increase of serum albumin (from to )? Decrease of hemodialysis prognostic index (from to at the end of treatment; P,.05) 430 kcal/d Increase of dry weight (10.49 kg; P 5.04) and decrease of C-reactive protein ( 1.69 mg/ L; P 5.01) 54 g/glucose 1 57 g/protein/wk No significant increase of serum albumin with S (from to ; P 5.12) and decrease without S (from to ; P 5.04) ARTIFICIAL NUTRITI IN HEMODIALYSIS 217

6 218 BOSSOLA ET AL for HD, over a period of 6 month. Unfortunately, 17 patients (20%) refused to ingest the oral and 10 (11.7%) showed decreased compliance ingesting less than 75% of prescribed nutritional. At the end of the study, in the 39 patients who completed the study, a significant increase was observed in serum albumin (from to g/dl) and prealbumin (from to mg/ dl) levels and in the SGA score. Steiber et al. 17 screened 117 patients on HD by use of the HD- PNI (Hemodialysis Prognostic Nutrition Index, which is calculated from baseline data as a linear mathematical equation using the level of serum albumin, level of serum creatinine, and number of days and times hospitalized). Then, they administered S for 3 months to 26 patients at high risk (HD-PNI 0.8 or higher) while maintaining the normal nutritional regimen in 91 patients at low risk (HD-PNI less than 0.8). In the S group, the HD-PNI score was reduced significantly (from to ; P,.05) while it remained unchanged in the patients who received the normal nutritional regimen. In the prospective, comparative study of Scott et al., patients on HD received standard care or S (with each HD session thrice weekly for 3 months). Mean serum albumin levels remained essentially unchanged between baseline and month 3 both in the S group ( versus ) and in the standard care group ( versus ). In addition to habitual diets, Ewers et al. 19 administered oral unsaturated fat supplements (430 kcal, 47 g of fat, 26.5 g of monounsaturated fatty acids) and 3 g of marine n-3 polyunsaturated fatty acids daily for 6 weeks to 40 chronic patients on HD. Then, the patients were switched to habitual diet only, for an additional 6 weeks. In the 14 patients who completed the study, a significant increase in body weight and decrease in C-reactive protein levels were observed. The study of Acchiardo et al. 20 only assessed the effect of S on survival in patients on HD. The study included 108 patients on HD who were divided into two groups a control group of 54 patients who did not receive S and a treatment group of 54 patients who received S for a unknown period of time. The annual mortality rates were similar in the two groups. However, patients who received S and survived 5 years had a significant increase in their protein catabolic rate (from to ) and serum albumin levels ( to ). Some studies have evaluated the safety and efficacy of oral amino acids supplements (Table 3). Apart from early studies that were nonrandomized and included a small number of patients, two recent trials led to interesting results. Eustace et al. 22 demonstrated that oral amino acid supplements in hypoalbuminemic patients on HD resulted in a significant improvement in serum albumin levels, grip strength, and Short Form Health Survey (SF-12) mental health score but not in serum amino acid levels, SF-12 physical health score, or anthropometric measures. Hiroshige et al. 23 randomized 28 malnourished patients to receive daily branched chain amino acid (BCAA) (12 g/day) or placebo. After 6 months, anthropometric indices and serum albumin levels showed a statistically significant increase in the BCAA group. After exchanging BCAA for placebo, spontaneous oral food intake decreased, although the favorable nutritional status persisted for the next 6 months, suggesting that the normalization of plasma BCAA levels can reduce anorexia and improve energy and protein intakes in patients on HD. Overall, it seems that S may improve serum albumin levels and/or other nutritional parameters in patients on HD, whereas there are insufficient data to assess their effect on clinical outcome. In addition, poor compliance may be a key limiting factor for S efficacy. Intradialytic Parenteral Nutrition IDPN has the advantage of providing calories and proteins during HD treatment without the need to establish a central venous line. The nutrients are infused into the blood returning from the dialyzer to the patient. The effect of IDPN on protein metabolism of HD patients has been extensively studied by Pupim et al. in two recent prospective, randomized studies (Table 4). In the first trial, 7 patients were studied 2 hours before, during, and 2 hours following an HD session with or without IDPN, using a primed constant infusion of L-(1-13 C)leucine and L-(ring- 2 H 5 ) phenylalanine. As result, IDPN promoted a large increase in whole-body protein synthesis and a significant decrease in wholebody proteolysis, along with a significant increase in forearm muscle protein synthesis. The net result

7 ARTIFICIAL NUTRITI IN HEMODIALYSIS 219 Table 3. Effects of Oral Protein Supplements in Patients on Hemodialysis: Nonrandomised, Controlled Trials and Cross-over Trials Type of Oral Supplementation Protein Intake Effects Author No. of Patients Type of Study Duration (mo) 1 Mixture of EAA and NEAA? Increase of EAA:NEAA ratio Mastroiacovo et al., themselves 36 HD Patients were controls for Eustace et al., HD and PD Randomized controlled 3 EAA 10.8 Increase of serum albumin (10.22 (0.03, 0.40) g/dl in the EAA group versus the placebo group Hiroshige et al., HD Randomized controlled 12 BCAA 12 With BCAA serum albumin increase (from 3.1 to 3.9 g/dl; P #.01) BCCAA, branched chain amino acids; EAA, essential amino acids; HD, hemodialysis; NEAA, nonessential amino acids; PD, peritoneal. was a change from an essentially catabolic state to a highly positive protein balance, in both wholebody and forearm muscle compartments. 24 More recently, the same authors, measuring the plasma enrichments of ( 13 C)leucine and ( 13 C)ketoisocaproate after infusion of ( 13 C)leucine, showed that IDPN improves the fractional synthetic rate of albumin during HD in parallel with a significant improvements in whole-body protein synthesis. 25 Interestingly, Pupim et al. 26 also demonstrated that exercise combined with IDPN, compared to IDPN alone, promoted two-fold increases in forearm muscle essential amino acid uptake and net muscle protein accretion during HD. An interesting finding of the studies of Pupim et al. was that the observed anabolic effects of IDPN were rapidly reversed during the postdialysis period when the IDPN was no longer being infused. These results imply that IDPN provides only a transient improvement in uremia and HD-associated catabolism and cannot effectively correct these prolonged catabolic effects. Studies that examined the potential benefits of IDPN in terms of correction of malnutrition (Table 5) are characterized by various and numerous biases: absence of randomized control groups, dietary intake of food not controlled or monitored, size of the study population too small for a valid statistical analysis, data not adjusted for the comorbid conditions of the patients, measurement only of nutritional outcomes with morbidity and mortality rarely evaluated, and energy and protein intakes often inappropriate Overall, the results of most of these studies show that IDPN is associated with an increase in body weight and/or improvement of nutritional parameters. Four studies only assessed the effect of IDPN on survival (Table 6). Three retrospective trials showed that IDPN increases survival In the study of Foulks et al., of 72 hypoalbuminemic patients on HD who received IDPN for 6 months experienced an increase of body weight of at least 10% and showed a significant reduction of hospitalization rate and increase of survival. Capelli et al. 39 compared the mortality rate in a group of 50 patients who received IDPN and in a group of 31 patients who did not. Nondiabetic patients received an average of 725 kcal/hd treatment and diabetic patients received an average of 670 kcal/hd treatment. The average length of treatment was 9 months. Overall, there was no

8 220 BOSSOLA ET AL Table 4. Effects of Intradialytic Parenteral Nutrition (IDPN) on Protein Metabolism Reference No. of Patients Protein-Calorie Intake/d Duration (mo) Effects Pupim et al., cal/h Few hours Increase in whole-body protein synthesis, decrease in wholebody proteolysis, increase in forearm muscle protein synthesis Pupim et al., cal/h Few hours Increase of albumin fractional synthetic rate Pupim et al., cal/h with or without exercise Few hours Exercise augments the acute anabolic effects of IDPN statistically significant difference in the percentage of deaths between IDPN-treated (36%) and untreated (48%; P 5.27) groups. Similarly, no difference was observed in the percentage of deaths between IDPN-treated and untreated patients in diabetic (50% versus 54; P 5.83) and in nondiabetic (26% versus 44%; P 5.21) groups. Using the Cox proportional hazards survival analysis, a significantly increased survival was observed with the use of IDPN (relative risk ; P,.01). In the study of Chertow et al., patients on HD who received one or more infusions of IDPN during 1991 were retrospectively compared with 22,517 unexposed controls. At lower levels of albumin (3.0 g/dl or less) and creatinine levels greater than 8.0 mg/dl, the odds of death was 3.14 (95% CI, ) in the IDPN group and 4.93 (95% CI, ) in the control group, resulting in a odds ratio of 0.64 (95% CI, ; P,.01). With serum albumin of 3.0 g/dl or less and creatinine levels less than 8.0 mg/dl, the odds of death was 5.45 (95% CI, ) in the IDPN group and 8.62 (95% CI, 5.95 and 12.49) in the control group, resulting in and odds ratio of 0.63 (p,0.01). With serum albumin levels.3.0 and,3.5 g/ dl, the odds of death of patients who received IDPN compared with that of controls. In contrast, in patients with serum albumin levels greater than 4.0 g/dl, IDPN with respect to controls was associated with increased mortality (odds ratio: 2.60 [CI, ]). More recently, a larger, randomized study 41 showed that IDPN associated with S (93 patients), compared with S alone (93 patients), did not improve 2-year mortality, hospitalization rate, Karnofsky score, BMI, or laboratory nutritional parameters. However, multivariate analysis showed that an increase in prealbumin levels (greater than 30 mg/l within 3 months) independently predicted a 54% decrease in 2-year mortality as well as reduced hospitalizations and improved general well-being as measured by the Karnofsky score. As suggested by the authors of the study, these negative results question the study power. Indeed, the power was calculated to be 78% and a tentative estimation of sample size using the 1-year efficacy observed in the study showed that a minimum of 1364 patients in each group would have been necessary to potentially observe a difference with a power of 80%. Interestingly, a study conducted in 1993, including patients who met the Medicare eligibility requirements for IDPN, demonstrated that although IDPN improved serum albumin levels significantly, no significant improvement in quality of life could be demonstrated. 42 Conclusion Malnutrition is a major issue in the long-term management of ESRD patients on maintenance dialysis, adversely affecting morbidity, mortality, functional activity, and quality of life. Its multifactorial pathogenesis implies a multidisciplinary effort including nutritional, metabolic, and pharmacological interventions. If food intake is reduced because of anorexia, BCAA supplements (12 g/daily) may be safely used, without bearing the risk of adverse effects or poor adherence to treatment. Chronic use of oral nutritional supplements is safe and may be useful in terms of improvement of nutritional parameters such as serum albumin and body weight. However, it remains to be clarified if the use of S is associated with increased survival. IDPN seems to improve nutritional parameters such as serum albumin

9 Table 5. Effects of Intradialytic Parenteral Nutrition (IDPN) on Nutritional Status in Hemodialysis Patients Reference No. of Patients Duration (mo) Protein-Calorie Intake/d Effects Snyder et al., Glucose (125 g) 1 lipid (50 g) 1 amino None acids (42.5) Schulman et al., kcal/kg g/protein/kg 1 GH Increase of serum albumin (from to g/dl; P..05), transferrin (from to mg/dl; P,.002) Hiroshige et al., Glucose 50% (200 ml) 1 essential amino acids 7% (200 ml) 1 lipid emulsion 20% (200 ml) Weight increase with IDPN (from to4365 kg; P,.05) and decrease without IDPN (from to4366; P,.05); serum albumin increase with IDPN (from to g/dl; P,.01) and decrease without IDPN (from to ; P,.01); serum transferrin increase with IDPN (from to mg/dl; P,.01) and decrease without IDPN (from to ; P,.05) Mortelmans et al., Glucose 50% (250 ml)1 lipid (250 ml) 1 amino acids 7% (250 ml) Increase of body weight (from to kg; P,.05), serum prealbumin (from to g/l) and transferrin (from to g/l) Berneis et al., Glucose 15% (37.5 g/h) 1 lipid (12.5 g/h) Increase of lean (from to kg; P,.003) and fat (from to kg; P,.02) body mass Krause et al., Children 1 3 Glucose 1 amino acids 1 fat 20% Increase of total lymphocyte count (from 1403 to 2006 cells/ml at 3 mo) Cherry et al., Glucose 50% 250 ml 1 lipid emulsion 20% Body weight increase, serum albumin increase 250 ml 1 amino acids 10% 250 or 500 ml Czekalski et al., $6 Amino acids 10% 500 ml Increase of serum albumin (from to ; P,.001); improvement of SGA (from median 16 points to median 11 points; P,.01) Orellana et al., ? Weight and BMI increase in 6 patients with organic malnutrition. No effect in patients with psychosocial-related malnutrition Joannidis et al., Glucose 1 amino acids 1 lipid emulsion 20% vs control Increase of body weight with IDPN (from to ; P 5.03) while no changes without IDPN (from to ; P..05) and increase of BMI with IDPN (from to ; P 5.03) but not without IDPN (from to ; P..05) Dezfuli et al., ? With serum albumin,3.0, a 3.5-times increased likelihood of serum albumin correction by IDPN ARTIFICIAL NUTRITI IN HEMODIALYSIS 221

10 222 BOSSOLA ET AL Table 6. Effects of Intradialytic Parenteral Nutrition (IDPN) on Survival in Hemodialysis Patients Reference No. of Patients Type of Study Duration (mo) Type of IDPN Effects The 45 patients who had a weight increase had lower mortality Foulks, Retrospective 6 Glucose 1 lipids 1 amino acids Increase of serum albumin; no statistically significant difference in the percentage of deaths between IDPNtreated (36%) and untreated (48%; P 5.27) At Cox analysis, a significantly increased survival was observed with IDPN (relative risk ; P,.01). Capelli et al., Retrospective 9 Glucose 1 lipids 1 amino acids With albumin #3.0 g/dl and creatinine levels. 8.0 mg/dl, odds ratio (CI, 0.44 and 0.92; P,.01). With serum albumin #3.0 g/dl and creatinine levels,8.0 mg/dl, odds ratio (P,.01). With serum albumin levels.3.0 and,3.5 g/dl, the odds ratio for death of patients who received IDPN compared with that of controls. With serum albumin levels.4.0 g/dl, odds ratio [CI, ]) Chertow et al., Retrospective 6 Glucose 1 lipids 1 amino acids Survival at 2 y was similar in IDPN and control groups (59% versus 61%) 12 Glucose 1 lipids 1 amino acids 1 S versus S alone Cano NJM et al., Prospective randomized controlled and body weight. Data on survival are conflicting and it useful to underline that the sole prospective, randomized, controlled study so far conducted has shown that IDPN does not influence long-term survival. However, when other nutritional therapeutic strategies are unavailable, IDPN may be potentially useful. But this must be assessed through randomized, controlled studies. In conclusion, it seems that further, adequate studies are needed to more accurately clarify the role of both S and IDPN in the prevention and treatment of malnutrition in chronic patients on HD. References 1. Locatelli F, Fouque D, Heimburger O, et al: Nutritional status in dialysis patients: a European consensus. Nephrol Dial Transplant 17: , Dukkipati R, Kopple JD: Causes and prevention of proteinenergy wasting in chronic kidney failure. Semin Nephrol 29: 39-49, Bossola M, Tazza L, Luciani G: Mechanisms and treatment of anorexia in end-stage renal disease patients on hemodialysis. J Ren Nutr 19:2-9, Mehrotra R, Berman N, Alistwani A, et al: Improvement of nutritional status after initiation of maintenance hemodialysis. Am J Kidney Dis 40: , Pupim LB, Kent P, Caglar K, et al: Improvement in nutritional parameters after initiation of chronic hemodialysis. Am J Kidney Dis 40: , Bossola M, Muscaritoli M, Tazza L, et al: Malnutrition in hemodialysis patients: what therapy? Am J Kidney Dis 46: , Kuhlmann MK, Scmidt F, Kohler H: Oral nutritional support in malnourished patients on HD: preliminary results of a randomised controlled study (abstract). J Am Soc Nephrol 8: 199A, Cockhram DB, Hensley MK, Rodriguez M, et al: Safety and tolerance of medical nutritional products as sole sources of nutrition in people on hemodialysis. J Ren Nutr 8:25-33, Sharma M, Rao M, Jacob S, Jacob CK: A controlled trial intermittent enteral nutrient in maintenance hemodialysis patients. J Ren Nutr 12: , Fouque D, McKenzie J, de Mutsert R, et al, and the Renilon Multicentre Trial Study Group: Use of a renal-specific oral supplement by haemodialysis patients with low protein intake does not increase the need for phosphate binders and may prevent a decline in nutritional status and quality of life. Nephrol Dial Transplant 23: , Cuppari L, Medeiros FA, Papini HF, et al: Effectiveness of oral energy-protein in severely malnourished hemodialysis patients. J Renal Nutr 4: , Beutler KT, Park GK, Wilkowsky MJ: Effect of oral on nutrition indicators in hemodialysis patients. J Ren Nutr 7:77-82, Shah NA, Mueller BA, Thomas J, et al: Effects of supplemental enteral nutrition on nutritional status and quality of life in ESRD patients receiving hemodialysis (abstract). J Am Soc Nephrol 10:303A, 1999.

11 ARTIFICIAL NUTRITI IN HEMODIALYSIS Patel MG, Kitchen S, Milligan PJ: Effect of dietary supplements on the npcr in stable hemodialysis patients. J Ren Nutr 10:69-75, Wilson B, Fernandez-Madrid A, Hayes A, et al: Comparison of the effects of two early intervention strategies on the health outcomes of malnourished hemodialysis patients. J Ren Nutr 11: , Caglar K, Fedje L, Dimmitt R, et al: Therapeutic effects of oral nutritional during hemodialysis. Kidney Int 62: , Steiber AL, Handu DJ, Cataline DR, et al: The impact of nutrition intervention on a reliable morbidity and mortality indicator: the hemodialysis-prognostic nutrition index. J Ren Nutr 13: , Scott MK, Shah NA, Vilay AM, et al: Effects of peridialytic oral supplements on nutritional status and quality of life in chronic hemodialysis patients. J Ren Nutr 19: , Ewers B, Riserus U, Marckmann P: Effects of unsaturated fat dietary supplements on blood lipids and on markers of malnutrition and inflammation in hemodialysis patients. J Ren Nutr 19: , Acchiardo SR, Riley ML: Five years experience with oral nutritional supplements (S) in hemodialysis (HD) patients. Are they useful (abstract)? J Am Soc Nephrol 13:415A, Mastroiacovo P, Pace V, Sagliaschi G: Aminoacids for dialysis patients. Clin Ther 15: , Eustace JA, Coresh J, Kutchey C, et al: Randomized double-blind trial of oral essential amino acids for dialysis-associated hypoalbuminemia. Kidney Int 2000;57: , Hiroshige K, Sonta T, Suda T, et al: Oral of branched-chain amino acid improves nutritional status in elderly patients on chronic hemodialysis. Nephrol Dial Transplant 16: , Pupim L, Flakoll PJ, Broillette JR, et al: Intradialytic parenteral nutrition improves protein and energy homeostasis in chronic hemodialysis patients. J Clin Invest 110: , Pupim L, Flakoll PJ, Ikizler TA: Nutritional acutely increases albumin fractional synthetic rate in chronic hemodialysis patients. J Am Soc Nephrol 15: , Pupim L, Flakoll PJ, Levenhagen DK, et al: Exercise augments the acute anabolic effects of intradialytic parenteral nutrition in chronic hemodialysis patients. Am J Physiol Endocrinol Metab 286:E589-E597, Snyder S, Bergen C, Sigler MH, et al: Intradialytic parenteral nutrition in chronic hemodialysis patients. ASAIO Trans 37: M373-M375, Schulman G, Wingard RL, Hutchinson RL, et al: The effects of recombinant human growth hormone and intradialytic parenteral nutrition in malnourished hemodialysis patients. Am J Kidney Dis 21: , Hiroshige K, Iwamoto M, Kabashima N, et al: Prolonged use of intradialysis parenteral nutrition in elderly malnourished chronic hemodialysis patients. Nephrol Dial Transplant 13: , Mortelmans AK, Duym P, Vandenbroucke J, et al: Intradialytic parenteral nutrition in malnourished hemodialysis patients: a prospective long-term study. JPEN 23:90-95, Berneis K, Iseli-Scahub J, Garbani E, et al: Effects of intradialytic parenetral nutrition in chronic hemodialysis patients with malnutrition: a pilot study. Wien Klin Wochenschr 12: , Krause I, Shamir R, Davidovits M, et al: Intradialytic parenteral nutrition in malnourished children treated with hemodialysis. J Ren Nutr 12:55-59, Cherry N, Shalansky K: Efficacy of intradialytic parenteral nutrition in malnourished hemodialysis patients. Am J Health Syst Pharm 15: , Czekalski S, Hozejowski R: Intradialytic aminoacids in hemodialysis patients with malnutrition: results of a multicenter cohort study. J Ren Nutr 14:82-88, Orellana P, Juarez-Congelosi M, Goldstein SL: Intradialytic parenteral nutrition treatment and biochemical marker assessment for malnutrition in adolescent maintenance hemodialysis patients. J Ren Nutr 15: , Joannindis M, Rauchenzauner M, Leiner B, et al: Effect of intradialytic parenteral nutrition in patients with malnutritioninflammation complex syndrome on body weight, inflammation, serum lipids and adipocytokines: results of a pilot study. Eur J Clin Nutr 62: , Dezfuli A, Scholl D, Lindenfeld SM, et al: Severity of hypoalbuminemia predicts response to intradialytic parenteral nutrition in hemodialysis patients. J Ren Nutr 19: , Foulks CJ: The effect of intradialytic parenteral nutrition on hospitalization rate and mortality in malnourished hemodialysis patients. J Ren Nutr 4:5-10, Capelli JP, Kushner H, Camiscioli TC, et al: Effect of intradialytic parenteral nutrition on mortality rates in end-stage renal disease care. Am J Kidney Dis 23: , Chertow GM, Ling J, Lew NL, et al: The association of intradialytic parenteral nutrition administration with survival in hemodialysis patients. Am J Kidney Dis 24: , Cano NJM, Fouque D, Roth H, et al: the French Study Group for Nutrition in Dialysis. Intradialytic parenteral nutrition does not improve survival in malnourished hemodialysis patients: a 2-year multicenter, prospective, randomised study. J Am Soc Nephrol 18: , Siskind MS, Lien YH: Effect of intradialytic parenteral nutrition on quality of life in hemodialysis patients. Int J Artif Organs 16: , 1993