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Use of Intradialytic Parenteral Nutrition in Hemodialysis Patients
EDITORIAL
'Use of Intradialytic Parenteral Nutrition in Hemodialysis Patients Marsha Wolfson, MD
A
SIGNIFICANT NUMBER of patients treated with maintenance dialysis for endstage renal disease suffer from protein-calorie malnutrition. !-5 The causes of malnutrition in these patients include anorexia and inadequate food intake due to dietary restrictions, loss ofnutrients into the dialysate, medications that interfere with food absorption and appetite, and frequent intercurrent illnesses. 6 Anorexia may be caused by inadequate dialysis? as well as by other factors associated with advanced renal failure. Malnutrition may be associated with increased morbidity and mortality in this patient population.4,8 Accordingly, strategies to improve the nutritional status of patients treated using dialysis are critical to improving the well being of these patients as well as potentially reducing hospitalizations and permitting better patient rehabilitation, thereby leading to reduced overall treatment costs. However, numerous studies evaluating a variety of nutritional interventions in dialysis patients have failed to demonstrate any clear benefit from the treatment of malnutrition. 9-!! In this issue of the American Journal a/Kidney Diseases, Capelli et al!2 report their findings from a retrospective, nonrandomized study evaluating the provision of parenteral nutrition during hemodialysis (IDPN) on mortality rates. They conclude that IDPN resulted in reduced mortality rates when compared with patients who did not receive IDPN. Although the results of this study are encouraging, several factors should be considered before recommending this treatment for all malnourished hemodialysis patients. The authors used IDPN for the treatment of malnutrition because they believed that previous From the Medical Service, Departments o/Veterans Affairs Medical Center and Medicine, Oregon Health Sciences University, Portland, OR. Address reprint requests to Marsha Wo/json, MD, Nephrology Section 111-e, Portland VA Medical Center, 3710 SW US Veterans Hospital Rd, PO Box 1034, Portland, OR 97207. This is a US government work. There are no restrictions on its use. 0272-6386/94/2306-0013$0.00/0 856
studies that provided oral nutritional supplementation failed to demonstrate any benefit. 9,!! Although it is true that the articles quoted did not show improvement in nutritional status, it is important to recognize some of the weaknesses in the studies referenced. For one thing, as the authors point out, many of the patients studied were not malnourished 10; therefore, it would be difficult to demonstrate any improvement in nutritional status in these patients. Another reason oral supplements used in these early studies failed to improve nutritional status is because they did not provide either calories or complete protein but only provided essential amino acids. 9 These early studies were based on the success of essential amino acids in limiting urea production and maintaining well being in patients with advanced renal failure who were not treated with dialysis.!3 Other investigators have been skeptical of the ability of poorly nourished dialysis patients to tolerate more complete oral supplements, but no studies have been performed to test whether complete oral nutritional supplementation would improve nutritional status or morbidity and mortality. The present study also fails to answer this question, because it was not a controlled trial. In addition, it is a nonrandomized, retrospective analysis in which the only outcome measure is survival rate. The treatment group included patients with a decreased serum albumin concentration «3.5 g/dL) or at least one of the following findings: actual body weight 10% less than ideal and/or 10% or more total weight loss extending over 2 months. Patients were then given dietary counseling and/or oral nutritional supplements for 2 months. If there was no response to these interventions, patients were given IDPN. Patients not treated with IDPN served as the control group. The treatment group had their oral supplements discontinued, and IDPN was provided over a period of 30 months. Despite the fact that one element of patient selection was low body weight, body weight at baseline was not significantly different in the survivors whether they were treated or not treated. However, body weight was significantly reduced in the nonsurvivors as a
American Journal of Kidney Diseases, Vol 23, No 6 (June), 1994: pp 856-858
USE OF IDPN IN HEMODIALYSIS
group when compared with the survivors. In addition, both treated and untreated nonsurvivors had significantly lower body weights at the end of 8 months when compared with the survivors. These results are important and would suggest that low body weight and weight loss may be significant predictors of mortality rates. Clear separation of the treated and untreated groups cannot be made based on body weight. However, body weight does separate survivors from nonsurvivors, independent of treatment. This raises the question of why the nonsurvivors with low body weight were not offered IDPN. It is unclear from this study whether the untreated patients with low body weight or continued weight loss had other serious underlying illnesses that would have made response to treatment unlikely and, therefore, were not offered any nutritional intervention. Failure to clearly separate the treatment groups is a major weakness of retrospective nonrandomized trials. Despite the findings from Lowrie et al 8 that a depressed serum albumin concentration is associated with decreased survival rates, this article fails to corroborate this association, although the treated survivors did attain the highest serum albumin concentrations (differences were not statistically significant). In addition, despite the described methods that presumably separated treated patients from untreated patients on the basis of serum albumin, there were no differences in the baseline serum albumin concentrations between the treated and untreated survivors and nonsurvivors. If anything, the nontreated survivors had slightly lower serum albumin concentrations as compared with the treated survivors (Table 5),12 although this difference does not appear to be statistically significant. However, it does raise the question of how the groups were actually selected and again points out one of the weaknesses of nonrandomized, retrospective studies. In the control group dietary supplements were continued, but "poor patient compliance led to discontinuance after 3 months." 12 Because oral supplements were only available to the control group for 3 months whereas the treated group had nutritional intervention for over 8 months (and no response to treatment was noted until at least 6 months of IDPN treatment was performed), this study does not provide a valid comparison between oral and intravenous nutritional
857
supplementation. No information is provided as to what led to "poor patient compliance l2 " in the untreated group. The authors state that an equivalent outcome is unlikely with oral supplementation "because of the multiple factors adversely affecting the gastrointestinal system in nutritionally depleted patients and the poor compliance in continuous use of these agents. 12" The references cited to corroborate this statement come from single case histories and not from controlled trials. In addition to the possibility that the patients who were not offered IDPN had other serious underlying conditions that would preclude successful intervention, it is also possible that the patients who were not offered IDPN were not given careful dietary instruction and feedback. Often, just making an intervention focuses the patient on nutritional issues and improves dietary compliance. The untreated patients may not have had the same nutritional focus as the treated patients. Finally, no information is provided on food intake during the study. Cano and coinvestigators found that institution of IDPN was shortly followed by improved dietary intake. 14 It is likely that a short-term intervention that improves nutritional status may also improve appetite and overall dietary intake, and this may be the reason for the improvement in weight gain and survival rate. The authors raise the issue of economic constraints on the use ofIDPN. Indeed, it is worthwhile to note that this treatment is often more costly than the dialysis procedure itself. If less costly methods of improving nutritional status, and therefore survival rates, could be found, then IDPN would be unnecessary. In addition, if IDPN could be used in carefully selected patients as a short-term treatment until appetite improved and oral intake could increase, the cost might be justified. However, until a carefully controlled study that compares various nutritional interventions in similar patient groups clearly demonstrates a benefit ofIDPN over other, less costly nutritional supplements, one should read the findings of this study with caution. The important findings from this study appear to be that weight loss or reduced body weight may be important predictors of a reduced survival rate in maintenance dialysis patients, and that nutritional intervention may be successful in im-
MARSHA WOLFSON
858
proving survival rates. Further studies to identify the most efficient and cost-effective ways to improve nutritional status are needed, especially in these times of reduced funding for patient care. REFERENCES I. Thunberg BJ, Swamy AP, Cestero RVM: Cross-sectional and longitudinal nutritional measurements in maintenance hemodialysis patients. Am J CIin Nutr 34:2005-2012, 1981 2. Young GA, Swanepoel CR, Croft MR, Hobson SM, Parsons FM: Anthropometry and plasma valine, amino acids, and proteins in the nutritional assessment of hemodialysis patients. Kidney Int 21:492-499, 1982 3. Wolfson M, Strong CJ, Minturn D, Gray DK, Kopple JD: Nutritional status and lymphocyte function in maintenance hemodialysis patients. Am J CIin Nutr 37:547-555, 1984 4. Marckman P: Nutritional status of patients on hemodialysis and peritoneal dialysis. CIin Nephrol 29:75-78, 1988 5. Young GA, Kopple JD, Lindholm B, Vonesh EF, De Vecchi A, Scalamogna A, Castel nova C, Oreopoulos DG, Anderson GH, Bergstrom J, DiChiro J, Gentile D, Nissenson A, Sakhrani L, Brownjohn AM, Nolph KD, Prowant BF, Algrim CE, Martis L, Serkes KD: Nutritional assessment of continuous ambulatory peritoneal dialysis patients: An international study. Am J Kidney Dis 27:462-471, 1991 6. Grodstein GP, Blumenkramtz MJ, Kopple JD: Nutritional and metabolic response to catabolic stress in uremia. Am J CIin Nutr 33:1411-1416,1980
7. Hakim RM, Levin N: Malnutrition in hemodialysis patients. Am J Kidney Dis 21:125-137,1993 8. Lowrie EG, Lew NL: Death risk in hemodialysis patients: The predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 15:458-482, 1990 9. Phillips ME, Havard J, Howard JP: Oral essential amino supplementation in patients on maintenance hemodialysis. CIin Nephrol 9:241-248, 1978 10. Hecking E, Kohler H, Zobel R, Lemmel E-M, Mader H, Opferkuch W, Prellwitz W, Keirn HF, Muller D: Treatment with essential amino acids in patients on chronic hemodialysis: A double blind cross-over study. Am J CIin Nutr 31:18211826, 1978 II. Piraino AJ, Firpo JJ, Powers DV: Prolonged hyperalimentation in catabolic chronic dialysis therapy patients. J Parenter Enteral Nutr 5:466-477, 1981 12. Capelli JP, Kushner H, Camiscioli TC, Chen S-M, Torres MA: Effect of intradialytic parenteral nutrition on mortality rates in end-stage renal disease care. Am J Kidney Dis 23:808-816,1994 13. Bergstrom J, Furst P, Noree L-O: Treatment of chronic uremic patients with protein poor diet and oral supply of essential amino acids I. Nitrogen balance studies. Clin Nephrol 3:187-193,1975 14. Cano N, Labastie-Coeyrehourcq J, Lacombe P, Stroumza P, Di Costanzo-Dufetel J, Durbec JP, Coudray-Lucas C, Cynober L: Peridialytic parenteral nutrition with lipids and amino acids in malnourished hemodialysis patients. Am J Clin Nutr 52:726-730, 1990
'Use of Intradialytic Parenteral Nutrition in Hemodialysis Patients Marsha Wolfson, MD
A
SIGNIFICANT NUMBER of patients treated with maintenance dialysis for endstage renal disease suffer from protein-calorie malnutrition. !-5 The causes of malnutrition in these patients include anorexia and inadequate food intake due to dietary restrictions, loss ofnutrients into the dialysate, medications that interfere with food absorption and appetite, and frequent intercurrent illnesses. 6 Anorexia may be caused by inadequate dialysis? as well as by other factors associated with advanced renal failure. Malnutrition may be associated with increased morbidity and mortality in this patient population.4,8 Accordingly, strategies to improve the nutritional status of patients treated using dialysis are critical to improving the well being of these patients as well as potentially reducing hospitalizations and permitting better patient rehabilitation, thereby leading to reduced overall treatment costs. However, numerous studies evaluating a variety of nutritional interventions in dialysis patients have failed to demonstrate any clear benefit from the treatment of malnutrition. 9-!! In this issue of the American Journal a/Kidney Diseases, Capelli et al!2 report their findings from a retrospective, nonrandomized study evaluating the provision of parenteral nutrition during hemodialysis (IDPN) on mortality rates. They conclude that IDPN resulted in reduced mortality rates when compared with patients who did not receive IDPN. Although the results of this study are encouraging, several factors should be considered before recommending this treatment for all malnourished hemodialysis patients. The authors used IDPN for the treatment of malnutrition because they believed that previous From the Medical Service, Departments o/Veterans Affairs Medical Center and Medicine, Oregon Health Sciences University, Portland, OR. Address reprint requests to Marsha Wo/json, MD, Nephrology Section 111-e, Portland VA Medical Center, 3710 SW US Veterans Hospital Rd, PO Box 1034, Portland, OR 97207. This is a US government work. There are no restrictions on its use. 0272-6386/94/2306-0013$0.00/0 856
studies that provided oral nutritional supplementation failed to demonstrate any benefit. 9,!! Although it is true that the articles quoted did not show improvement in nutritional status, it is important to recognize some of the weaknesses in the studies referenced. For one thing, as the authors point out, many of the patients studied were not malnourished 10; therefore, it would be difficult to demonstrate any improvement in nutritional status in these patients. Another reason oral supplements used in these early studies failed to improve nutritional status is because they did not provide either calories or complete protein but only provided essential amino acids. 9 These early studies were based on the success of essential amino acids in limiting urea production and maintaining well being in patients with advanced renal failure who were not treated with dialysis.!3 Other investigators have been skeptical of the ability of poorly nourished dialysis patients to tolerate more complete oral supplements, but no studies have been performed to test whether complete oral nutritional supplementation would improve nutritional status or morbidity and mortality. The present study also fails to answer this question, because it was not a controlled trial. In addition, it is a nonrandomized, retrospective analysis in which the only outcome measure is survival rate. The treatment group included patients with a decreased serum albumin concentration «3.5 g/dL) or at least one of the following findings: actual body weight 10% less than ideal and/or 10% or more total weight loss extending over 2 months. Patients were then given dietary counseling and/or oral nutritional supplements for 2 months. If there was no response to these interventions, patients were given IDPN. Patients not treated with IDPN served as the control group. The treatment group had their oral supplements discontinued, and IDPN was provided over a period of 30 months. Despite the fact that one element of patient selection was low body weight, body weight at baseline was not significantly different in the survivors whether they were treated or not treated. However, body weight was significantly reduced in the nonsurvivors as a
American Journal of Kidney Diseases, Vol 23, No 6 (June), 1994: pp 856-858
USE OF IDPN IN HEMODIALYSIS
group when compared with the survivors. In addition, both treated and untreated nonsurvivors had significantly lower body weights at the end of 8 months when compared with the survivors. These results are important and would suggest that low body weight and weight loss may be significant predictors of mortality rates. Clear separation of the treated and untreated groups cannot be made based on body weight. However, body weight does separate survivors from nonsurvivors, independent of treatment. This raises the question of why the nonsurvivors with low body weight were not offered IDPN. It is unclear from this study whether the untreated patients with low body weight or continued weight loss had other serious underlying illnesses that would have made response to treatment unlikely and, therefore, were not offered any nutritional intervention. Failure to clearly separate the treatment groups is a major weakness of retrospective nonrandomized trials. Despite the findings from Lowrie et al 8 that a depressed serum albumin concentration is associated with decreased survival rates, this article fails to corroborate this association, although the treated survivors did attain the highest serum albumin concentrations (differences were not statistically significant). In addition, despite the described methods that presumably separated treated patients from untreated patients on the basis of serum albumin, there were no differences in the baseline serum albumin concentrations between the treated and untreated survivors and nonsurvivors. If anything, the nontreated survivors had slightly lower serum albumin concentrations as compared with the treated survivors (Table 5),12 although this difference does not appear to be statistically significant. However, it does raise the question of how the groups were actually selected and again points out one of the weaknesses of nonrandomized, retrospective studies. In the control group dietary supplements were continued, but "poor patient compliance led to discontinuance after 3 months." 12 Because oral supplements were only available to the control group for 3 months whereas the treated group had nutritional intervention for over 8 months (and no response to treatment was noted until at least 6 months of IDPN treatment was performed), this study does not provide a valid comparison between oral and intravenous nutritional
857
supplementation. No information is provided as to what led to "poor patient compliance l2 " in the untreated group. The authors state that an equivalent outcome is unlikely with oral supplementation "because of the multiple factors adversely affecting the gastrointestinal system in nutritionally depleted patients and the poor compliance in continuous use of these agents. 12" The references cited to corroborate this statement come from single case histories and not from controlled trials. In addition to the possibility that the patients who were not offered IDPN had other serious underlying conditions that would preclude successful intervention, it is also possible that the patients who were not offered IDPN were not given careful dietary instruction and feedback. Often, just making an intervention focuses the patient on nutritional issues and improves dietary compliance. The untreated patients may not have had the same nutritional focus as the treated patients. Finally, no information is provided on food intake during the study. Cano and coinvestigators found that institution of IDPN was shortly followed by improved dietary intake. 14 It is likely that a short-term intervention that improves nutritional status may also improve appetite and overall dietary intake, and this may be the reason for the improvement in weight gain and survival rate. The authors raise the issue of economic constraints on the use ofIDPN. Indeed, it is worthwhile to note that this treatment is often more costly than the dialysis procedure itself. If less costly methods of improving nutritional status, and therefore survival rates, could be found, then IDPN would be unnecessary. In addition, if IDPN could be used in carefully selected patients as a short-term treatment until appetite improved and oral intake could increase, the cost might be justified. However, until a carefully controlled study that compares various nutritional interventions in similar patient groups clearly demonstrates a benefit ofIDPN over other, less costly nutritional supplements, one should read the findings of this study with caution. The important findings from this study appear to be that weight loss or reduced body weight may be important predictors of a reduced survival rate in maintenance dialysis patients, and that nutritional intervention may be successful in im-
MARSHA WOLFSON
858
proving survival rates. Further studies to identify the most efficient and cost-effective ways to improve nutritional status are needed, especially in these times of reduced funding for patient care. REFERENCES I. Thunberg BJ, Swamy AP, Cestero RVM: Cross-sectional and longitudinal nutritional measurements in maintenance hemodialysis patients. Am J CIin Nutr 34:2005-2012, 1981 2. Young GA, Swanepoel CR, Croft MR, Hobson SM, Parsons FM: Anthropometry and plasma valine, amino acids, and proteins in the nutritional assessment of hemodialysis patients. Kidney Int 21:492-499, 1982 3. Wolfson M, Strong CJ, Minturn D, Gray DK, Kopple JD: Nutritional status and lymphocyte function in maintenance hemodialysis patients. Am J CIin Nutr 37:547-555, 1984 4. Marckman P: Nutritional status of patients on hemodialysis and peritoneal dialysis. CIin Nephrol 29:75-78, 1988 5. Young GA, Kopple JD, Lindholm B, Vonesh EF, De Vecchi A, Scalamogna A, Castel nova C, Oreopoulos DG, Anderson GH, Bergstrom J, DiChiro J, Gentile D, Nissenson A, Sakhrani L, Brownjohn AM, Nolph KD, Prowant BF, Algrim CE, Martis L, Serkes KD: Nutritional assessment of continuous ambulatory peritoneal dialysis patients: An international study. Am J Kidney Dis 27:462-471, 1991 6. Grodstein GP, Blumenkramtz MJ, Kopple JD: Nutritional and metabolic response to catabolic stress in uremia. Am J CIin Nutr 33:1411-1416,1980
7. Hakim RM, Levin N: Malnutrition in hemodialysis patients. Am J Kidney Dis 21:125-137,1993 8. Lowrie EG, Lew NL: Death risk in hemodialysis patients: The predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 15:458-482, 1990 9. Phillips ME, Havard J, Howard JP: Oral essential amino supplementation in patients on maintenance hemodialysis. CIin Nephrol 9:241-248, 1978 10. Hecking E, Kohler H, Zobel R, Lemmel E-M, Mader H, Opferkuch W, Prellwitz W, Keirn HF, Muller D: Treatment with essential amino acids in patients on chronic hemodialysis: A double blind cross-over study. Am J CIin Nutr 31:18211826, 1978 II. Piraino AJ, Firpo JJ, Powers DV: Prolonged hyperalimentation in catabolic chronic dialysis therapy patients. J Parenter Enteral Nutr 5:466-477, 1981 12. Capelli JP, Kushner H, Camiscioli TC, Chen S-M, Torres MA: Effect of intradialytic parenteral nutrition on mortality rates in end-stage renal disease care. Am J Kidney Dis 23:808-816,1994 13. Bergstrom J, Furst P, Noree L-O: Treatment of chronic uremic patients with protein poor diet and oral supply of essential amino acids I. Nitrogen balance studies. Clin Nephrol 3:187-193,1975 14. Cano N, Labastie-Coeyrehourcq J, Lacombe P, Stroumza P, Di Costanzo-Dufetel J, Durbec JP, Coudray-Lucas C, Cynober L: Peridialytic parenteral nutrition with lipids and amino acids in malnourished hemodialysis patients. Am J Clin Nutr 52:726-730, 1990