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Nutritional Support in Renal Failure
Current Strategies in Surgical Nutrition
0039-6109/91 $0.00
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Nutritional Support in Renal Failure
Charlene Compher, MS, RD,* James L. Mullen, MD,t and Clyde F. Barker, MDt.
Provision of nutritional support to patients with renal insufficiency requires consideration of their limitations in the disposal of byproducts as well as their altered requirements during the course of disease. Necessary dialysis procedures may be modified to accommodate concomitant nutritional support.
ACUTE RENAL FAILURE Patients with acute renal failure may present with hypermetabolism and hypercatabolism. Patients with postoperative acute renal failure have increased energy expenditures by indirect calorimetry of 130% to 190% of predicted values, with higher levels associated with a higher mortality rate. The hypermetabolism is secondary to the underlying process causing or coincident with the acute renal failure; but acute renal failure itself does not induce a hypermetabolic state. Patients with multiple organ failure including acute renal failure have energy expenditures no different from those with multiple organ failure but without acute renal failure,73 whereas the energy expenditure in acute renal failure without sepsis is normal. 69 Assessment Measuring energy expenditure is important to individualize patient care. In a diverse population of hospitalized patients, we documented actual energy expenditures from 70% to 140% of predicted values. 30 Similar variability occurs in patients with acute renal failure, and such marked *Nutrition Support Dietitian Specialist, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania t Associate Professor of Surgery, University of Pennsylvania School of Medicine, and Director, Nutrition Support Service, and Surgeon, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania :j:Professor and Chairman, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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interindividual variation in resting energy expenditure (REE) emphasizes the importance of measuring energy expenditure. 68, 72 The catabolic response to acute renal failure is quite variable, with losses of 2 to 30 g of nitrogen per day. 13, 27 Mitch and Wilmore 57 proposed a severity index linking the degree of catabolism and the mortality rate using urea nitrogen appearance (Table 1). Animal studies have shown an increase in muscle protein degradation and a 25% decrease in protein synthesis in acute renal failure. 14, 28, 48 This increase in catabolism may be secondary to the insulin resistance of acute renal failure or to high levels of glucagon and catecholaminesY Metabolic assessment provides information for individualization of nutrient requirements. Measurement of energy expenditure by indirect calorimetry provides a severity index as well as an accurate guide to caloric prescription. Urea nitrogen appearance (Table 1) quantifies protein catabolism and provides a guide to needed protein intake. Voluntary nutrient intake usually is inadequate because of the associated primary organ failures or uremic symptoms of anorexia, nausea, and vomiting. Limitations in renal function may produce abnormalities in the metabolism of various nutrients. Carbohydrate metabolism is disturbed by a peripheral tissue resistance to the hypoglycemic effect of insulin, which occurs early during acute renal failure. Together with increased hepatic glucose production associated with the hypermetabolic state, this results in elevated blood glucose levels and increased insulin requirements. Lipid clearance is also impaired by the insulin resistance and by a decrease in lipoprotein lipase. Serum triglyceride levels are helpful for monitoring lipid clearance. Depending on the level of renal compromise, fluid overload may occur and necessitate fluid restriction or dialysis. Elevated levels of blood urea nitrogen (BUN) and creatinine earmark the retention of nitrogenous compounds and are accompanied by elevations of serum magnesium, potassium, and phosphorus. Nutritional status assessment is difficult because of a variety of factors. The sudden decline in renal function complicates the use of transport proteins as nutritional status indicators, as all may be diluted by fluid overload. Also, exogenous albumin may be infused to promote fluid removal, ruling out the use of its serum level as a nutritional marker. Prealbumin may be elevated secondary to limited renal clearance, not to adequate nutrient intake. Transferrin may be the most reliable nutritional Table 1. Urea Nitrogen Appearance (UNA) and Clinical Course UNA'
2
3-10 >10
CAUSE OF ARF
MORTALITY (%)
Drug toxicity Surgery ± infection Hypotension and severe injury/sepsis
70-80 80
20
*UNA = urine urea nitrogen + serial change in BUN; ARF = acute renal failure. Change in BUN = (BUN day 2 (giL) - BUN day 1) (weight kg) (0.6) From Mitch W Wilmore D: Nutritional considerations in the treatment of acute renal failure. In Brenner B, Lazarus J (eds): Acute Renal Failure. Philadelphia, WB Saunders, 1983, p 757.
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marker in acute renal failure. Change in usual body weight prior to the onset of renal failure is an important marker of chronic malnutrition, with an actual loss of 10% of the usual body weight within 8 weeks a clinically significant loss.77 Weight change is difficult to evaluate after the onset of acute renal failure if fluid excretion is limited, mandating the concept of "estimated dry weight." Anthropometric measurements, including triceps skinfold and midarm muscle circumference, may be useful if fluid overload is not significant but should be normalized to National Health and Nutrition Examination Survey Standards. 32 Effects of Nutritional Support Nutritional support improves the extent and speed of recovery from acute renal failure, preserves renal function, and decreases host nitrogen losses. More frequent return of renal function was reported with essential amino acids than with isocaloric glucose infusions in less-catabolic patients. 2 However, with diverse, highly catabolic patients, no difference was seen in the preservation of renal function with infusion of essential versus nonessential plus essential amino acids, although the severe clinical course of these patients may have had a greater impact on their renal outcome than did the composition of the total parenteral nutrition solution. 10, 26, 48, 56 Lesser renal insufficiency was seen in rats after acute tubular necrosis when essential and nonessential amino acids were given than with normal saline infusion. Increased phospholipid synthesis in the renal cortex suggested healing of the damaged cell membrane at a faster rate when both nonessential and essential amino acids are infused. 78 No difference in the frequency of recovery of renal function was seen in rats after acute renal failure in a comparison of essential amino acids, essential plus nonessential amino acids, and essential plus high branched-chain amino acids. 30 The effect of nutritional support on morbidity and mortality has been extensively explored in hospitalized patients with normal renal function. We showed decreased morbidity in malnourished patients who received preoperative total parenteral nutrition. 16 The strong correlation between poor transport protein status, especially low albumin levels, and increased morbidity is well recognized. 5 The effects of nutritional support on morbidity and mortality in acute renal failure have been variable, but most investigators emphasize the benefits of feeding. Improved patient survival was noted when essential amino acids rather than isocaloric glucose were infused; in reality, this study was a comparison of patients who were partially fed with those who were not fed. 2, 10, 48 No difference in survival was seen when essential versus nonessential plus essential amino acids were provided isonitrogenously12, 56 or with higher nonessential plus essential than essential amino acid intake. 27 These studies all examined small numbers of patients with acute renal failure, so a type II statistical error is possible. Improved nitrogen balance with no increase in BUN or creatinine occurred when patients with acute renal failure were given 150 g rather than 75 g/day of nonessential plus essential amino acids. 72 Higher protein intake may increase the requirement for dialysis because of the fluid needed to deliver additional amino acids and the additional urea generated, and the necessary dialysis procedures may be complicated by hypotension or catheter sepsis.
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The acute effects of nutrient infusion on the kidney are interesting. Amino acid infusion causes an increase in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) which is mediated by angiotensin and prostaglandins. 15, 68, 75 Lipid infusions cause no such change. 65 Whether such hemodynamic effects have any implications for long-term preservation of renal function is unknown. The effects of nutritional support on the metabolic derangements of acute renal failure vary with the patient's prior nutritional state, the level of catabolism, nutrient intake, and residual renal function plus the effects of dialysis. Significant catabolism of muscle occurs in response to cytokines in order to generate amino acids for gluconeogenesis and the synthesis of acute-phase proteins, This catabolism of muscle releases K, P, and Mg as well as urea, causing increased serum levels in patients with acute renal failure. When patients are malnourished, serum levels of K, Mg, and P decrease with provision of adequate calories and protein. The mechanism appears to be the movement of these nutrients intracellularly. The greater the degree of catabolism and the less the pre-existing malnutrition, the less likely is it that there will be any beneficial effect on serum micronutrient levels. Mildly catabolic patients who receive total parenteral nutrition with essential amino acids have decreases in the serum levels of K and P.2, 22 Patients who have severe hypercatabolism do not show this effect. 13 Intake of K, Mg, and P can be controlled parenterally, as oral intake is generally minimal. Commonly used medications also supply Mg, and others bind phosphorus, so careful prescription of medications is helpful. Because dialysis procedures remove variable quantities of K, Mg, P, and fluid, and because the dialysis procedure of choice may change with the patient's clinical state, daily monitoring of these micronutrients and fluid status is essential. Subjects with normal or starvation metabolism have a decrease in muscle catabolism in response to nutrient supply. In normal subjects, the protein catabolic rate increases when dietary protein intake is reduced to less than 0.4 g/kg. Tracer studies note a stepwise decrease in protein catabolism when the dietary intake increases from 1 to 2 g of protein/kg per day. 62, 76 Abel and Dudrick and their coworkers showed a similar decrease in urea generation in acute renal failure in patients with limited hypercatabolism.2, 22 In highly catabolic patients, the response to nutrient supply is to increase protein synthesis. In burned patients, protein synthesis increases to a level equal to the protein catabolic rate when the protein intake is increased from 1.5 to 2.2 g/kg.42 A similar process in patients with acute renal failure was suggested by nitrogen balance studies.72 However, it may not be possible in all hypercatabolic patients to increase the level of protein synthesis to that of protein catabolism. The effects of nutritional support on nutritional status in patients with acute renal failure have not been well explored. Positive nitrogen balance has been achieved,22, 27, 72 although serial transport protein levels are not available. Serum amino acid profiles before and after amino acid infusion evidence utilization of all administered amino acids. 2 Caloric balance is difficult to maintain, but no long-term effects of weight change in acute
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renal failure are known. Nutritional support is known to replete serum transport proteins and to promote protein synthesis and weight gain in subjects with normal renal function. Amino acid requirements are based on the protein catabolic rate as measured by urea generation. Protein intake adequate to achieve a positive nitrogen balance is the appropriate goal. Patients with limited catabolism may have a positive nitrogen balance with a low intake (0.6 g of protein/ kg), whereas others who are more catabolic may require 2 glkg for a positive nitrogen balance. If dialysis is not feasible, protein intake may be curtailed by the volume of fluid and urea the patient can excrete. Amino acid profiles can consist of either essential amino acids alone or a mixture of essential and nonessential amino acids. Current consensus favors a mixed profile of nonessential and essential amino acids. Better nitrogen utilization is achieved with nonessential plus essential amino acids than with essential amino acids provided isonitrogenously,46 and nonessential plus essential amino acids decrease BUN levels better than essential' amino acids and are needed for optimal healing of the nephron cell membrane. 79 The protein metabolism goals are to enhance synthesis and to decrease catabolism. Both catabolized muscle protein and the portion of parenteral amino acids that is oxidized appear as urea. Amino acids used for synthesis do not appear as urea, and if a patient's catabolism of body protein stores decreases with feeding, urea levels may decline. 2. 65 The urea, electrolytes, P, and Mg generated by hypercatabolism also require dialysis for removal. Dialysis may likewise be required to remove fluid and the byproducts of high protein and caloric intake. Caloric requirements in acute renal failure are determined in the usual fashion. Caloric overfeeding is undesirable, as it produces hepatic steatosis, excess CO 2 production, catecholamine release, and accretion of fat more than muscle. Caloric underfeeding produces loss of body fat stores, which may be desirable; however, this may have a negative impact on nitrogen balance unless protein intake is increased. Recommended caloric intake should be less than 75% of the total energy expenditure (TEE) if fat loss is desired, at TEE if fat weight maintenance is the goal, and 130% of TEE to induce fat gain. Measured REE is assumed to be 75% of TEE in sick hospitalized patients. Other nutrient requirements are individualized by serial monitoring of serum levels. Phosphorus, magnesium, and potassium requirements vary widely, and these substances may need to be deleted from or supplemented in the nutrient solutions. Hypercalcemia in patients with acute renal failure, critical illness, and immobilization may necessitate deletion of vitamins A and D and of Ca from the nutrient solutions. 29. 34
CHRONIC RENAL FAILURE The nutritional effects of end-stage renal failure include caloric, protein, and micronutrient intake limitations in the setting of dialytic protein loss and normometabolism. Both patients requiring hemodialysis and those with
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chronic renal failure not receiving dialysis are normometabolic. 59 • 69 This implies that their weight loss over time is attributable to inadequate caloric intake. As multiple dietary restrictions are common (Na, K, P, fluid, protein, Ca), food intake decreases and gradual weight loss occurs. In a study of 168 stable patients with end-stage renal disease but without underlying diabetes or malignancy, a mean intake of 23 kcallkg and 0.9 g of proteinlkg per day was achieved despite nutrition counseling to achieve 35 kcallkg per day and 0.8 to 1.4 g of proteinlkg. 70 In 50 patients with endstage renal disease and a range of diagnoses, 44% had moderate to severe marasmic malnutrition. 19 More than half of patients undergoing hemodialysis (54%) or chronic ambulatory peritoneal dialysis (56%) had moderate to severe depletion of fat stores, muscle mass, transferrin levels, and body weight. 53 Limitations in serum protein status have been linked with increased morbidity. Significantly more hospitalizations were observed in patients with limited protein intake, particularly in those whose dialysis treatment was less vigorous than the usual treatment. 3, 70 A higher frequency of hospitalizations was likewise observed in patients when serum albumin levels were less than normal, with a graduated increase in the risk of hospitalization as the albumin level decreased. 50 More than two thirds of this 12,000-patient group had below-normal levels of albumin. Metabolic bone disease further complicates the nutritional support of patients with chronic renal failure. Because the kidney has limited ability to hydroxylate vitamin D to its active form, control of Ca and P metabolism is inadequate, and these minerals leave bone. Momentary low Ca levels stimulate parathyroid hormone secretion, and the kidney is unable to produce calcitonin to turn this off.lO, 20 Nutritional support should be provided with limited P and Ca intake to avoid metastatic calcification and osteoporotic bone disease. Although osteoporosis is the most common type of bone disease, osteomalacia and other types have been observed as well. Treatment of the metabolic bone disease of end-stage renal disease currently involves use of a phosphorus-binding medication, dietary P restriction, or both in order to control the serum Ca-P product, Parathyroidectomy has also been used to control the production of parathyroid hormone and to decrease its effects on Ca and P removal from bone. Intravenous calcitonin has recently been infused during the hemodialysis treatment to decrease parathyroid hormone secretion. The current preference in phosphatebinding medications is for calcium-containing binders, with avoidance of aluminum hydroxide binders over the long term to prevent aluminum accumulation in bone and body fluids, Approximately 30% of patients with chronic renal failure have hypertriglyceridemia (>300 mg/dL) which is thought to be secondary to an increase in the production of very low-density lipoprotein and inadequate lipoprotein lipase secretion. 35 Low levels of high-density lipoproteincholesterol accompany hypertriglyceridemia, but hypercholesterolemia is unusual. When acute illness occurs in a patient with end-stage renal disease, protein requirements are increased, and hypermetabolism may occur. Urea generation (see Table 1) provides information about the protein catabolic rate. The increase in catabolic rate also increases the production of K, Mg,
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P, and urea and may necessitate additional dialysis treatments for removal of these toxins as well as the fluid and byproducts of optimal nutritional support. Measurement of energy expenditure provides guidance for caloric requirement. NEPHROTIC SYNDROME The _nutritional effects of the nephrotic syndrome are primarily evidenced by hypoalbuminemia and hypercholesterolemia. The hypoalbuminemia is attributable to increased urinary excretion of albumin secondary to a loss of selectivity and charge characteristics of the glomerular membrane. 44 Albumin synthesis is supranormal in nephrotic syndrome and correlates positively with urinary albumin 10ss.11 Cholesterol levels are inversely correlated with serum albumin levels, and the increase in cholesterol may be secondary to hepatic overproduction in response to the decreased blood viscosity.7 Hypertriglyceridemia is common because of increased production of very low-density lipoprotein and inadequate secretion of lipoprotein lipase and may limit the clearance of infused lipid. In addition to albumin, transferrin is lost in the urine of patients with nephrotic syndrome, and a low serum level may thus be unreliable as a nutritional marker. 23 With acute illness superimposed on chronic nephrotic syndrome, the rationale for nutritional support is to decrease the loss of body cell mass from catabolism. The effects of adequate protein intake in acutely ill patients with nephrotic syndrome are unknown. Nutrient requirements can be determined by metabolic assessment. Urea generation (Table 1) plus total protein in the urine guide protein intake in the acute setting. In chronic nephrotic syndrome, protein restriction to 0.6 glkg per day results in decreased urinary albumin losses and paradoxically increased serum albumin levels. 45 However, protein restriction in the face of increased protein catabolism leads only to the loss of body protein stores. A daily protein intake of 1 to 1.5 g/kg may be indicated.
NUTRIENT DELIVERY ROUTE Most sick patients in renal failure require forced feeding because of reduced voluntary nutrient intake. Primary attempts should be focused on using enteral feedings if bowel function permits. Enteral formulas can be selected to limit intake of fluid, Na, K, Ca, P, and Mg. To decrease gastrointestinal symptoms when splanchnic blood flow is less because of dialysis, patients should not receive enteral feedings during hemodialysis. Enteral feeding tolerance may be difficult to evaluate in patients who are also receiving peritoneal dialysis, and patients with uremic symptoms of nausea and vomiting may have difficulty maintaining a nasoenteric feeding tube. Parenteral nutrients should be used if the enteral route is not functional or accessible. Concentrated glucose, amino acid, and lipid solutions will minimize the volume of fluid required for optimal caloric and protein intake but will necessitate central venous access for delivery.
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ALTERNATIVE DELIVERY ROUTES Dialysis can be adapted for provision of nutrients. Peritoneal dialysis without amino acids in the dialysate generates a loss of 24 to 36 g of protein daily in sick patients. In patients with peritonitis, this loss increases to 36 to 44 g/day. 43 Stable patients on chronic ambulatory peritoneal dialysis without other illness lose only 10 g/day because they have only three or four exchanges per day, and peritonitis is less common. 33 Peritoneal dialysis provides significant caloric intake. Patients absorb 60% to 80% of the dialysate glucose,6 and this may provide 700 to 4000 kcal of glucose daily. Excess glucose supply from the combination of peritoneal dialysis and total parenteral nutrition results in elevation of hepatic enzymes in the serum. 52 Total parenteral nutrition with amino acids and no glucose may be optimal for patients receiving peritoneal dialysis who are relying on dialysate glucose. Chronic ambulatory peritoneal dialysis with 1.1% or 2% amino acids instead of glucose as dialysate has been well tolerated as judged symptomatically.8.37 The measured absorption of amino acids was 77%, and gastrointestinal side effects were minimized when the amino acids were buffered. Provision of full peritoneal parenteral nutrition has been explored in dogs. 61 On autopsy, peritoneal hyperplasia and phagocytosis were noted but no organ damage. Concurrent jejunal feedings are well tolerated if the feeding access site and wound are completely sealed. Gastric feedings may be tolerated poorly because of abdominal fullness when dialysate is in the peritoneum. Abdominal distention secondary to poor tolerance of enteral feedings is difficult to detect in the presence of peritoneal dialysis. Continuous hemofiltration (CAVH, SCUF, CAVHD) involves no protein intake and documented losses of 11 g of protein per day. 18, 21 Fortythree per cent of glucose infused is retained, providing 500 kcal daily, assuming a 1.5% glucose dialysate. 71 The primary advantage of continuous hemofiltration for nutrition support is its optimal removal of fluid volume (up to 24 Uday), which allows more parenteral intake. Enteral access is usually contraindicated in patients with such severe hemodynamic instability that continuous hemofiltration is required. Hemodialysis provides no protein intake and a loss of 9 to 12 g of amino acids per treatment. Caloric intake and losses are minimal. Hemodialysis can be used to provide nutrients via the venous return line. Such intradialytic parenteral nutrition increases transport proteins,4O, 50, 78 promotes positive nitrogen balance, 78, 81 and induces weight gain17, 64, 67 in stable malnourished patients with end-stage renal disease. The use of intradialytic parenteral nutrition in patients with greater protein requirements because of acute illness has not been systematically studied. The limitations of intradialytic parenteral nutrition are related to the patient's tolerance of rapid infusion of glucose, lipid, and fluid. Hemodialyzed patients with end-stage renal disease have only 75% of normal lipid clearance. 49 Hemodialysis heparin may increase lipid clearance. No changes in cardiac output or pulmonary capillary wedge pressure occur with intakes of 0.3 g of lipid/kg per hour. 1 The lipid infusion rate should be limited to
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1 glkg per hour. 36 Unfortunately, the symptoms of intolerance to rapid infusion of lipid mimic those of intolerance to excess fluid volume removal with dialysis. Lipids should not be used if serum triglyceride levels are greater than 300 mg!dL before dialysis, indicating poor lipid clearance. The provision of glucose calories via intradialytic parenteral nutrition requires gradual increases in glucose intake with blood sugar monitoring and administration of the necessary insulin if the blood sugar exceeds 300 mg! dL. Glucose administration should not exceed the known maximal oxidation rate of 1. 2 g!kg per dialysis treatment. 80 Intradialytic parenteral nutrition with amino acids has been studied minimally. Ninety per cent of infused amino acids were retained when 40 g of protein and 850 kcal of glucose were provided over 4 hours.8] No acute symptoms secondary to the peritoneal administration of amino acids have been described.
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19. Compher C: Nutrition assessment in chronic renal failure. Nutr Support Services 7:18, 1985 20. Conger J: Metastatic calcification in chronic renal failure. Kidney 13:13, 1980 21. Davenport A, Roberts N: Amino acid losses during continuous high-flux hemofiltration in the critically ill patient. Crit Care Med 17:1010, 1989 22. Dudrick SJ, Steiger E, Long JM: Renal failure in surgical patients: Treatment with intravenous essential amino acids and hypertonic glucose. Surgery 86:180, 1970 23. Ellis D: Anemia in the course of nephrotic syndrome secondary to transferrin depletion. J Pediatr 90:953, 1977 24. Elwyn D, Gump F, Munro H, et al: Changes in nitrogen balance of depleted patients with increasing infusions of glucose. Am J Clin Nutr 32:1597, 1979 25. Feinstein E: Total parenteral nutritional support of patients with acute renal failure. Nutr Clin Pract 3:9, 1988 26. Feinstein E, Blumenkrantz M, Healy M, et al: Clinical and metabolic responses to parenteral nutrition in acute renal failure: A controlled double-blind study. Medicine 60:124, 1981 27. Feinstein E, Kopple J, Silberman H, et al: Total parenteral nutrition with high or low nitrogen intakes in patients with acute renal failure. Kidney lnt 26:S319, 1983 28. Fluegel-Link R, Salusky I, Jones M, et al: Protein and amino acid metabolism in the posterior hemicorpus of acutely uremic rats. Am J Physiol 244:E623, 1983 29. Forster J, Querusio L, Burchard K, et al: Hypercalcemia in critically ill surgical patients. Ann Surg 202:512, 1985 30. Foster G, Knox L, Dempsey D, et al: Caloric requirement in total parenteral nutrition. J Am Coll Nutr 6:231, 1987 31. Freund H, Muggia-Sullam M, LaFrance R, et al: The effect of different intravenous nutritional regimens on renal function during acute renal failure in the rat. JPEN 11:556, 1987 32. Frisancho AR: New standards of weight and body composition by frame size and height for assessment of nutritional status of adults and elderly. Am J Clin Nutr 40:808, 1984 33. Giordano G, DeSanto N, Capodicasa G, et al: Amino acid losses during CAPD. Clin Nephrol 14:230, 1980 34. Gleghorn E, Eisenberg L, Hack S, et al: Observations of vitamin A toxicity in three patients with renal failure receiving parenteral alimentation. Am J Clin Nutr 44:107, 1986 35. Grundy S: Management of hyperlipidemia of kidney disease. Kidney lnt 37:847, 1990 36. Hallberg D, Holm I, Obel A, et al: Fat emulsions for complete intravenous nutrition. Postgrad Med J 43:307, 1967 37. Hanning R, Balfe J, Zlotkin S: Effectiveness and nutritional consequences of amino acidbased vs glucose-based dialysis solutions in infants and children receiving CAPD. Am J Clin Nutr 46:22, 1987 38. Heidland A, Kult J: Longterm effects of essential amino acids supplementation on nitrogen excretion in patients on regular dialysis treatments. Clin Nephrol 3:234, 1975 39. Heifetz M, Morrissey J, Purkerson M, et al: Effect of dietary lipids on renal function in rats with subtotal nephrectomy. Kidney lnt 32:335, 1987 40. Hirschberg R, Kopple J: Effects of growth hormone on GFR and renal plasma flow in man. Kidney lnt 32:S21, 1987 41. Holmes J: lntradialytic parenteral nutrition. Cont Dial Nephrol 4:50, 1990 42. Jahoor F, Wolfe R: Regulation of protein catabolism. Kidney lnt 32:S81, 1987 43. Katirtzoglou A, Oreopoulos D, Husdan H, et al: Reappraisal of protein losses in patients undergoing continuous ambulatory peritoneal dialysis. Nephron 25:230, 1980 44. Kaysen G, Gambertoglio J, Jimenez I, et al: Effect of dietary protein intake on albumin homeostasis in nephrotic patients. Kidney lnt 29:572, 1986 45. Klahr S, Purkeson M: Effects of dietary protein on renal function and on the progression of renal disease. Am J Clin Nutr 47:146, 1988 46. Koppel J: Treatment of renal failure with defined formula diets. In Shils M (ed): Defined Formula Diets for Medical Purposes. Chicago, American Medical Association, 1977, p 113 47. Lee H, Talbot T: Nutrition in renal failure. Nutr Res Rev 2:1, 1989 48. Leonard CD, Luke RG, Siegel RR: Parenteral essential amino acids in acute renal failure. Urology 6:154, 1975
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49. Lindh A, Hylander B, Rossner S: Intralipid removal from plasma of uraemic and intensive care patients. Clin Nutr 8:145, 1989 50. Lowrie E, Lew N: 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, 1990 51. Madigan K, Olshan A, Yingling D: Effectiveness of intradialytic parenteral nutrition in diabetic patients with end-stage renal disease. J Am Diet Assoc 90:861, 1990 52. Manji N, Shikora S, McMahon M, et al: Peritoneal dialysis for acute renal failure: Overfeeding resulting from dextrose absorbed during dialysis. Crit Care Med 18:29, 1990 53. Markmann P: Nutritional status of patients on hemodialysis and peritoneal dialysis. Clin Nephrol 29:75, 1988 54. Mault J, Bartlett R, Dechert R, et al: Starvation: A major contribution to mortality in acute renal failure? Am Soc Artif Intern Organs 29:390, 1983 55. Miller R, Taylor W, Gentry W, et al: Indirect calorimetry in postoperative patients with acute renal failure. Am Surg 49:494, 1983 56. Mirtallo J, Schneider P, Mavki K, et al: A comparison of essential and general amino acid infusions in the nutritional support of patients with compromised renal function. JPEN 5:109, 1982 57. Mitch W, Wilmore D: Nutritional considerations in the treatment of acute renal failure. In Brenner B, Lazarus J (eds): Acute Renal Failure. Philadelphia, WB Saunders, 1983, p 743 58. Mitch W, May R, Clark A, et al: Influence of insulin resistance and amino acid supply on muscle protein turnover in uremia. Kidney Int 32:S1O, 1987 59. Monteon F, Laidlaw S, Shaib J, et al: Energy expenditure in patients with chronic renal failure. Kidney Int 30:741, 1986 60. Moore L, Acchiardo S: Aggressive nutritional supplementation in chronic hemodialysis patients. CRN Q 11:14, 1987 61. Moran J, Limon M, Mahedero G, et al: Long-term peritoneal nutrition in dogs: Metabolic and histopathologic results. Nutrition 5:89, 1989 62. Motil K, Matthews D, Bier D, et al: Whole-body leucine and lysine metabolism: Response to dietary protein intake in young men. Am J Physiol 240:E712, 1981 63. Mullen J, Buzby G, Matthews D, et al: Reduction of operative morbidity and mortality by combined preoperative and postoperative nutritional support. Ann Surg 102:604, 1980 64. Olshan A, Bruce J, Schwartz A: Intradialytic parenteral nutrition administration during outpatient hemodialysis. Dial Transplant 10:495, 1987 65. Pedersen E, Ladefoged S, Lauritsen H, et al: Intravenous lipid load and renal reserve. Clin Nutr 9:24, 1990 66. Pelosi G, Prioetti R: Total parenteral nutrition infusate: An approach to its optimal composition in post-trauma acute renal failure. Rescue 9:45, 1981 67. Piraino A, Firpo J, Powers D: Prolonged hyperalimentation in catabolic chronic dialysis therapy patients. JPEN 5:463, 1981 68. Ruilope L, Rodicio J, Robles R, et al: Influence of a low sodium diet on the renal response to amino acid infusions in humans. Kidney Int 31:992, 1987 69. Schneeweiss B, Graninger W, Stockenhuber F, et al: Energy metabolism in acute and chronic renal failure. Am J Clin Nutr 52:596, 1990 70. Schoenfeld P, Henry R, Laird N, et al: Assessment of nutritional status of the National Cooperative Dialysis Study population. Kidney Int 23:S80, 1983 71. Sigler M, Teehan B: Solute transport in continuous hemodialysis: A new treatment for acute renal failure. Kidney Int 32:562, 1987 72. Singer P, Bursztein S, Segal A, et al: Reduced morbidity in acute renal failure with high rates of amino acid (AA) infusion. Clin Nutr 9:23, 1990 73. Soop M, Forsberg E, Thorne A, et al: Energy expenditure in postoperative multiple organ failure with acute renal failure. Clin Nephrol 31:139, 1989 74. Spreiter S, Myers B, Swenson R: Protein-energy requirements in subjects with acute renal failure receiving intermittent hemodialysis. Am J Clin Nutr 33:1433, 1980 75. Stahl R, Kudelka S, Helmchen U: High protein intake stimulates glomerular prostaglandin formation in remnant kidneys. Am J Physiol 252:F1083, 1987
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76. Steffee W, Goldsmith R, Pencharz P, et al: Dietary protein intake and dynamic aspects of whole-body nitrogen metabolism in adult humans. Metabolism 25:281, 1976 77. Studley H: Percentage of weight loss: A basic indicator of surgical risk in patients with chronic peptic ulcer. JAM A 106:458, 1935 78. Thunberg B, Jain V, Patterson P: Nutritional measurements and urea kinetics to guide intradialytic hyperalimentation. Proc Dial Transplant For 10:22, 1980 79. Toback F: Amino acid enhancement of renal regeneration after acute tubular necrosis. Kidney 12:193, 1977 80. Wolfe R, O'Donnell T, Stone M, et al: Investigation of factors determining the optimal glucose infusion rate in total parenteral nutrition. Metabolism 29:892, 1980 81. Wolfson M, Jones M, Kopple J: Amino acid losses during hemodialysis with infusion of amino acids and glucose. Kidney Int 21:500, 1982
Address reprint requests to James L. Mullen, MD Nutrition Support Service Hospital of the University of Pennsylvania 4 Silverstein Pavilion 3400 Spruce Street Philadelphia, PA 19104
0039-6109/91 $0.00
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Nutritional Support in Renal Failure
Charlene Compher, MS, RD,* James L. Mullen, MD,t and Clyde F. Barker, MDt.
Provision of nutritional support to patients with renal insufficiency requires consideration of their limitations in the disposal of byproducts as well as their altered requirements during the course of disease. Necessary dialysis procedures may be modified to accommodate concomitant nutritional support.
ACUTE RENAL FAILURE Patients with acute renal failure may present with hypermetabolism and hypercatabolism. Patients with postoperative acute renal failure have increased energy expenditures by indirect calorimetry of 130% to 190% of predicted values, with higher levels associated with a higher mortality rate. The hypermetabolism is secondary to the underlying process causing or coincident with the acute renal failure; but acute renal failure itself does not induce a hypermetabolic state. Patients with multiple organ failure including acute renal failure have energy expenditures no different from those with multiple organ failure but without acute renal failure,73 whereas the energy expenditure in acute renal failure without sepsis is normal. 69 Assessment Measuring energy expenditure is important to individualize patient care. In a diverse population of hospitalized patients, we documented actual energy expenditures from 70% to 140% of predicted values. 30 Similar variability occurs in patients with acute renal failure, and such marked *Nutrition Support Dietitian Specialist, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania t Associate Professor of Surgery, University of Pennsylvania School of Medicine, and Director, Nutrition Support Service, and Surgeon, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania :j:Professor and Chairman, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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interindividual variation in resting energy expenditure (REE) emphasizes the importance of measuring energy expenditure. 68, 72 The catabolic response to acute renal failure is quite variable, with losses of 2 to 30 g of nitrogen per day. 13, 27 Mitch and Wilmore 57 proposed a severity index linking the degree of catabolism and the mortality rate using urea nitrogen appearance (Table 1). Animal studies have shown an increase in muscle protein degradation and a 25% decrease in protein synthesis in acute renal failure. 14, 28, 48 This increase in catabolism may be secondary to the insulin resistance of acute renal failure or to high levels of glucagon and catecholaminesY Metabolic assessment provides information for individualization of nutrient requirements. Measurement of energy expenditure by indirect calorimetry provides a severity index as well as an accurate guide to caloric prescription. Urea nitrogen appearance (Table 1) quantifies protein catabolism and provides a guide to needed protein intake. Voluntary nutrient intake usually is inadequate because of the associated primary organ failures or uremic symptoms of anorexia, nausea, and vomiting. Limitations in renal function may produce abnormalities in the metabolism of various nutrients. Carbohydrate metabolism is disturbed by a peripheral tissue resistance to the hypoglycemic effect of insulin, which occurs early during acute renal failure. Together with increased hepatic glucose production associated with the hypermetabolic state, this results in elevated blood glucose levels and increased insulin requirements. Lipid clearance is also impaired by the insulin resistance and by a decrease in lipoprotein lipase. Serum triglyceride levels are helpful for monitoring lipid clearance. Depending on the level of renal compromise, fluid overload may occur and necessitate fluid restriction or dialysis. Elevated levels of blood urea nitrogen (BUN) and creatinine earmark the retention of nitrogenous compounds and are accompanied by elevations of serum magnesium, potassium, and phosphorus. Nutritional status assessment is difficult because of a variety of factors. The sudden decline in renal function complicates the use of transport proteins as nutritional status indicators, as all may be diluted by fluid overload. Also, exogenous albumin may be infused to promote fluid removal, ruling out the use of its serum level as a nutritional marker. Prealbumin may be elevated secondary to limited renal clearance, not to adequate nutrient intake. Transferrin may be the most reliable nutritional Table 1. Urea Nitrogen Appearance (UNA) and Clinical Course UNA'
2
3-10 >10
CAUSE OF ARF
MORTALITY (%)
Drug toxicity Surgery ± infection Hypotension and severe injury/sepsis
70-80 80
20
*UNA = urine urea nitrogen + serial change in BUN; ARF = acute renal failure. Change in BUN = (BUN day 2 (giL) - BUN day 1) (weight kg) (0.6) From Mitch W Wilmore D: Nutritional considerations in the treatment of acute renal failure. In Brenner B, Lazarus J (eds): Acute Renal Failure. Philadelphia, WB Saunders, 1983, p 757.
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marker in acute renal failure. Change in usual body weight prior to the onset of renal failure is an important marker of chronic malnutrition, with an actual loss of 10% of the usual body weight within 8 weeks a clinically significant loss.77 Weight change is difficult to evaluate after the onset of acute renal failure if fluid excretion is limited, mandating the concept of "estimated dry weight." Anthropometric measurements, including triceps skinfold and midarm muscle circumference, may be useful if fluid overload is not significant but should be normalized to National Health and Nutrition Examination Survey Standards. 32 Effects of Nutritional Support Nutritional support improves the extent and speed of recovery from acute renal failure, preserves renal function, and decreases host nitrogen losses. More frequent return of renal function was reported with essential amino acids than with isocaloric glucose infusions in less-catabolic patients. 2 However, with diverse, highly catabolic patients, no difference was seen in the preservation of renal function with infusion of essential versus nonessential plus essential amino acids, although the severe clinical course of these patients may have had a greater impact on their renal outcome than did the composition of the total parenteral nutrition solution. 10, 26, 48, 56 Lesser renal insufficiency was seen in rats after acute tubular necrosis when essential and nonessential amino acids were given than with normal saline infusion. Increased phospholipid synthesis in the renal cortex suggested healing of the damaged cell membrane at a faster rate when both nonessential and essential amino acids are infused. 78 No difference in the frequency of recovery of renal function was seen in rats after acute renal failure in a comparison of essential amino acids, essential plus nonessential amino acids, and essential plus high branched-chain amino acids. 30 The effect of nutritional support on morbidity and mortality has been extensively explored in hospitalized patients with normal renal function. We showed decreased morbidity in malnourished patients who received preoperative total parenteral nutrition. 16 The strong correlation between poor transport protein status, especially low albumin levels, and increased morbidity is well recognized. 5 The effects of nutritional support on morbidity and mortality in acute renal failure have been variable, but most investigators emphasize the benefits of feeding. Improved patient survival was noted when essential amino acids rather than isocaloric glucose were infused; in reality, this study was a comparison of patients who were partially fed with those who were not fed. 2, 10, 48 No difference in survival was seen when essential versus nonessential plus essential amino acids were provided isonitrogenously12, 56 or with higher nonessential plus essential than essential amino acid intake. 27 These studies all examined small numbers of patients with acute renal failure, so a type II statistical error is possible. Improved nitrogen balance with no increase in BUN or creatinine occurred when patients with acute renal failure were given 150 g rather than 75 g/day of nonessential plus essential amino acids. 72 Higher protein intake may increase the requirement for dialysis because of the fluid needed to deliver additional amino acids and the additional urea generated, and the necessary dialysis procedures may be complicated by hypotension or catheter sepsis.
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The acute effects of nutrient infusion on the kidney are interesting. Amino acid infusion causes an increase in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) which is mediated by angiotensin and prostaglandins. 15, 68, 75 Lipid infusions cause no such change. 65 Whether such hemodynamic effects have any implications for long-term preservation of renal function is unknown. The effects of nutritional support on the metabolic derangements of acute renal failure vary with the patient's prior nutritional state, the level of catabolism, nutrient intake, and residual renal function plus the effects of dialysis. Significant catabolism of muscle occurs in response to cytokines in order to generate amino acids for gluconeogenesis and the synthesis of acute-phase proteins, This catabolism of muscle releases K, P, and Mg as well as urea, causing increased serum levels in patients with acute renal failure. When patients are malnourished, serum levels of K, Mg, and P decrease with provision of adequate calories and protein. The mechanism appears to be the movement of these nutrients intracellularly. The greater the degree of catabolism and the less the pre-existing malnutrition, the less likely is it that there will be any beneficial effect on serum micronutrient levels. Mildly catabolic patients who receive total parenteral nutrition with essential amino acids have decreases in the serum levels of K and P.2, 22 Patients who have severe hypercatabolism do not show this effect. 13 Intake of K, Mg, and P can be controlled parenterally, as oral intake is generally minimal. Commonly used medications also supply Mg, and others bind phosphorus, so careful prescription of medications is helpful. Because dialysis procedures remove variable quantities of K, Mg, P, and fluid, and because the dialysis procedure of choice may change with the patient's clinical state, daily monitoring of these micronutrients and fluid status is essential. Subjects with normal or starvation metabolism have a decrease in muscle catabolism in response to nutrient supply. In normal subjects, the protein catabolic rate increases when dietary protein intake is reduced to less than 0.4 g/kg. Tracer studies note a stepwise decrease in protein catabolism when the dietary intake increases from 1 to 2 g of protein/kg per day. 62, 76 Abel and Dudrick and their coworkers showed a similar decrease in urea generation in acute renal failure in patients with limited hypercatabolism.2, 22 In highly catabolic patients, the response to nutrient supply is to increase protein synthesis. In burned patients, protein synthesis increases to a level equal to the protein catabolic rate when the protein intake is increased from 1.5 to 2.2 g/kg.42 A similar process in patients with acute renal failure was suggested by nitrogen balance studies.72 However, it may not be possible in all hypercatabolic patients to increase the level of protein synthesis to that of protein catabolism. The effects of nutritional support on nutritional status in patients with acute renal failure have not been well explored. Positive nitrogen balance has been achieved,22, 27, 72 although serial transport protein levels are not available. Serum amino acid profiles before and after amino acid infusion evidence utilization of all administered amino acids. 2 Caloric balance is difficult to maintain, but no long-term effects of weight change in acute
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renal failure are known. Nutritional support is known to replete serum transport proteins and to promote protein synthesis and weight gain in subjects with normal renal function. Amino acid requirements are based on the protein catabolic rate as measured by urea generation. Protein intake adequate to achieve a positive nitrogen balance is the appropriate goal. Patients with limited catabolism may have a positive nitrogen balance with a low intake (0.6 g of protein/ kg), whereas others who are more catabolic may require 2 glkg for a positive nitrogen balance. If dialysis is not feasible, protein intake may be curtailed by the volume of fluid and urea the patient can excrete. Amino acid profiles can consist of either essential amino acids alone or a mixture of essential and nonessential amino acids. Current consensus favors a mixed profile of nonessential and essential amino acids. Better nitrogen utilization is achieved with nonessential plus essential amino acids than with essential amino acids provided isonitrogenously,46 and nonessential plus essential amino acids decrease BUN levels better than essential' amino acids and are needed for optimal healing of the nephron cell membrane. 79 The protein metabolism goals are to enhance synthesis and to decrease catabolism. Both catabolized muscle protein and the portion of parenteral amino acids that is oxidized appear as urea. Amino acids used for synthesis do not appear as urea, and if a patient's catabolism of body protein stores decreases with feeding, urea levels may decline. 2. 65 The urea, electrolytes, P, and Mg generated by hypercatabolism also require dialysis for removal. Dialysis may likewise be required to remove fluid and the byproducts of high protein and caloric intake. Caloric requirements in acute renal failure are determined in the usual fashion. Caloric overfeeding is undesirable, as it produces hepatic steatosis, excess CO 2 production, catecholamine release, and accretion of fat more than muscle. Caloric underfeeding produces loss of body fat stores, which may be desirable; however, this may have a negative impact on nitrogen balance unless protein intake is increased. Recommended caloric intake should be less than 75% of the total energy expenditure (TEE) if fat loss is desired, at TEE if fat weight maintenance is the goal, and 130% of TEE to induce fat gain. Measured REE is assumed to be 75% of TEE in sick hospitalized patients. Other nutrient requirements are individualized by serial monitoring of serum levels. Phosphorus, magnesium, and potassium requirements vary widely, and these substances may need to be deleted from or supplemented in the nutrient solutions. Hypercalcemia in patients with acute renal failure, critical illness, and immobilization may necessitate deletion of vitamins A and D and of Ca from the nutrient solutions. 29. 34
CHRONIC RENAL FAILURE The nutritional effects of end-stage renal failure include caloric, protein, and micronutrient intake limitations in the setting of dialytic protein loss and normometabolism. Both patients requiring hemodialysis and those with
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chronic renal failure not receiving dialysis are normometabolic. 59 • 69 This implies that their weight loss over time is attributable to inadequate caloric intake. As multiple dietary restrictions are common (Na, K, P, fluid, protein, Ca), food intake decreases and gradual weight loss occurs. In a study of 168 stable patients with end-stage renal disease but without underlying diabetes or malignancy, a mean intake of 23 kcallkg and 0.9 g of proteinlkg per day was achieved despite nutrition counseling to achieve 35 kcallkg per day and 0.8 to 1.4 g of proteinlkg. 70 In 50 patients with endstage renal disease and a range of diagnoses, 44% had moderate to severe marasmic malnutrition. 19 More than half of patients undergoing hemodialysis (54%) or chronic ambulatory peritoneal dialysis (56%) had moderate to severe depletion of fat stores, muscle mass, transferrin levels, and body weight. 53 Limitations in serum protein status have been linked with increased morbidity. Significantly more hospitalizations were observed in patients with limited protein intake, particularly in those whose dialysis treatment was less vigorous than the usual treatment. 3, 70 A higher frequency of hospitalizations was likewise observed in patients when serum albumin levels were less than normal, with a graduated increase in the risk of hospitalization as the albumin level decreased. 50 More than two thirds of this 12,000-patient group had below-normal levels of albumin. Metabolic bone disease further complicates the nutritional support of patients with chronic renal failure. Because the kidney has limited ability to hydroxylate vitamin D to its active form, control of Ca and P metabolism is inadequate, and these minerals leave bone. Momentary low Ca levels stimulate parathyroid hormone secretion, and the kidney is unable to produce calcitonin to turn this off.lO, 20 Nutritional support should be provided with limited P and Ca intake to avoid metastatic calcification and osteoporotic bone disease. Although osteoporosis is the most common type of bone disease, osteomalacia and other types have been observed as well. Treatment of the metabolic bone disease of end-stage renal disease currently involves use of a phosphorus-binding medication, dietary P restriction, or both in order to control the serum Ca-P product, Parathyroidectomy has also been used to control the production of parathyroid hormone and to decrease its effects on Ca and P removal from bone. Intravenous calcitonin has recently been infused during the hemodialysis treatment to decrease parathyroid hormone secretion. The current preference in phosphatebinding medications is for calcium-containing binders, with avoidance of aluminum hydroxide binders over the long term to prevent aluminum accumulation in bone and body fluids, Approximately 30% of patients with chronic renal failure have hypertriglyceridemia (>300 mg/dL) which is thought to be secondary to an increase in the production of very low-density lipoprotein and inadequate lipoprotein lipase secretion. 35 Low levels of high-density lipoproteincholesterol accompany hypertriglyceridemia, but hypercholesterolemia is unusual. When acute illness occurs in a patient with end-stage renal disease, protein requirements are increased, and hypermetabolism may occur. Urea generation (see Table 1) provides information about the protein catabolic rate. The increase in catabolic rate also increases the production of K, Mg,
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P, and urea and may necessitate additional dialysis treatments for removal of these toxins as well as the fluid and byproducts of optimal nutritional support. Measurement of energy expenditure provides guidance for caloric requirement. NEPHROTIC SYNDROME The _nutritional effects of the nephrotic syndrome are primarily evidenced by hypoalbuminemia and hypercholesterolemia. The hypoalbuminemia is attributable to increased urinary excretion of albumin secondary to a loss of selectivity and charge characteristics of the glomerular membrane. 44 Albumin synthesis is supranormal in nephrotic syndrome and correlates positively with urinary albumin 10ss.11 Cholesterol levels are inversely correlated with serum albumin levels, and the increase in cholesterol may be secondary to hepatic overproduction in response to the decreased blood viscosity.7 Hypertriglyceridemia is common because of increased production of very low-density lipoprotein and inadequate secretion of lipoprotein lipase and may limit the clearance of infused lipid. In addition to albumin, transferrin is lost in the urine of patients with nephrotic syndrome, and a low serum level may thus be unreliable as a nutritional marker. 23 With acute illness superimposed on chronic nephrotic syndrome, the rationale for nutritional support is to decrease the loss of body cell mass from catabolism. The effects of adequate protein intake in acutely ill patients with nephrotic syndrome are unknown. Nutrient requirements can be determined by metabolic assessment. Urea generation (Table 1) plus total protein in the urine guide protein intake in the acute setting. In chronic nephrotic syndrome, protein restriction to 0.6 glkg per day results in decreased urinary albumin losses and paradoxically increased serum albumin levels. 45 However, protein restriction in the face of increased protein catabolism leads only to the loss of body protein stores. A daily protein intake of 1 to 1.5 g/kg may be indicated.
NUTRIENT DELIVERY ROUTE Most sick patients in renal failure require forced feeding because of reduced voluntary nutrient intake. Primary attempts should be focused on using enteral feedings if bowel function permits. Enteral formulas can be selected to limit intake of fluid, Na, K, Ca, P, and Mg. To decrease gastrointestinal symptoms when splanchnic blood flow is less because of dialysis, patients should not receive enteral feedings during hemodialysis. Enteral feeding tolerance may be difficult to evaluate in patients who are also receiving peritoneal dialysis, and patients with uremic symptoms of nausea and vomiting may have difficulty maintaining a nasoenteric feeding tube. Parenteral nutrients should be used if the enteral route is not functional or accessible. Concentrated glucose, amino acid, and lipid solutions will minimize the volume of fluid required for optimal caloric and protein intake but will necessitate central venous access for delivery.
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ALTERNATIVE DELIVERY ROUTES Dialysis can be adapted for provision of nutrients. Peritoneal dialysis without amino acids in the dialysate generates a loss of 24 to 36 g of protein daily in sick patients. In patients with peritonitis, this loss increases to 36 to 44 g/day. 43 Stable patients on chronic ambulatory peritoneal dialysis without other illness lose only 10 g/day because they have only three or four exchanges per day, and peritonitis is less common. 33 Peritoneal dialysis provides significant caloric intake. Patients absorb 60% to 80% of the dialysate glucose,6 and this may provide 700 to 4000 kcal of glucose daily. Excess glucose supply from the combination of peritoneal dialysis and total parenteral nutrition results in elevation of hepatic enzymes in the serum. 52 Total parenteral nutrition with amino acids and no glucose may be optimal for patients receiving peritoneal dialysis who are relying on dialysate glucose. Chronic ambulatory peritoneal dialysis with 1.1% or 2% amino acids instead of glucose as dialysate has been well tolerated as judged symptomatically.8.37 The measured absorption of amino acids was 77%, and gastrointestinal side effects were minimized when the amino acids were buffered. Provision of full peritoneal parenteral nutrition has been explored in dogs. 61 On autopsy, peritoneal hyperplasia and phagocytosis were noted but no organ damage. Concurrent jejunal feedings are well tolerated if the feeding access site and wound are completely sealed. Gastric feedings may be tolerated poorly because of abdominal fullness when dialysate is in the peritoneum. Abdominal distention secondary to poor tolerance of enteral feedings is difficult to detect in the presence of peritoneal dialysis. Continuous hemofiltration (CAVH, SCUF, CAVHD) involves no protein intake and documented losses of 11 g of protein per day. 18, 21 Fortythree per cent of glucose infused is retained, providing 500 kcal daily, assuming a 1.5% glucose dialysate. 71 The primary advantage of continuous hemofiltration for nutrition support is its optimal removal of fluid volume (up to 24 Uday), which allows more parenteral intake. Enteral access is usually contraindicated in patients with such severe hemodynamic instability that continuous hemofiltration is required. Hemodialysis provides no protein intake and a loss of 9 to 12 g of amino acids per treatment. Caloric intake and losses are minimal. Hemodialysis can be used to provide nutrients via the venous return line. Such intradialytic parenteral nutrition increases transport proteins,4O, 50, 78 promotes positive nitrogen balance, 78, 81 and induces weight gain17, 64, 67 in stable malnourished patients with end-stage renal disease. The use of intradialytic parenteral nutrition in patients with greater protein requirements because of acute illness has not been systematically studied. The limitations of intradialytic parenteral nutrition are related to the patient's tolerance of rapid infusion of glucose, lipid, and fluid. Hemodialyzed patients with end-stage renal disease have only 75% of normal lipid clearance. 49 Hemodialysis heparin may increase lipid clearance. No changes in cardiac output or pulmonary capillary wedge pressure occur with intakes of 0.3 g of lipid/kg per hour. 1 The lipid infusion rate should be limited to
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1 glkg per hour. 36 Unfortunately, the symptoms of intolerance to rapid infusion of lipid mimic those of intolerance to excess fluid volume removal with dialysis. Lipids should not be used if serum triglyceride levels are greater than 300 mg!dL before dialysis, indicating poor lipid clearance. The provision of glucose calories via intradialytic parenteral nutrition requires gradual increases in glucose intake with blood sugar monitoring and administration of the necessary insulin if the blood sugar exceeds 300 mg! dL. Glucose administration should not exceed the known maximal oxidation rate of 1. 2 g!kg per dialysis treatment. 80 Intradialytic parenteral nutrition with amino acids has been studied minimally. Ninety per cent of infused amino acids were retained when 40 g of protein and 850 kcal of glucose were provided over 4 hours.8] No acute symptoms secondary to the peritoneal administration of amino acids have been described.
REFERENCES 1. Abel R, Fisch D, Grossman M: Hemodynamic effects of intravenous 20% soy oil emulsion following coronary bypass surgery. JPEN 7:534, 1983 2. Abel R, Beck C, Ahbott W, et al: Improved survival from acute renal failure after treatment with essential amino acids and glucose. N Engl J Med 288:695, 1973 3. Acchiardo S, Moore L, Latour P: Malnutrition as the main factor in morbidity and mortality of hemodialysis patients. Kidney Int 24:S199, 1983 4. Albert A, Takamatsu H, Fonkalsrud E: Absorption of glucose solutions from the peritoneal cavity in rabbits. Arch Surg 119:1247, 1984 5. Anderson CF, Wochos D: The utility of serum albumin values in the nutritional assessment of hospitalized patients. Mayo Clin Proc 57:181, 1982 6. Andersson G, Bergquist-Poppen M, Bergstrom J, et al: Glucose absorption from the dialysis fluid during peritoneal dialysis. Scand J Urol Nephrol 5:77, 1971 7. Appel G, Blum C, Chien S, et al: The hyperlipidemia of the nephrotic syndrome: Relation to plasma albumin concentration, oncotic pressure, and viscosity. N Engl J Med 312:1544, 1985 8. Arfeen S, Goodship T, Kirkwood A, et al: The nutritional/metabolic and hormonal effects of 9 weeks continuous ambulatory peritoneal dialysis with a 1% amino acid solution. Clin Nephrol 33:192, 1990 9. Avioli L, Teitelbaum S: Renal osteodystrophy. In Lawrence E, Earley E, Gottschalk C (eds): Diseases of the Kidney I. Boston, Little, Brown, 1979, p 307 10. Baek S, Makabali G, Bryan-Brown C, et al: The influence of total parenteral nutrition on the course of acute renal failure. Surg Gynecol Obstet 141:405, 1975 11. Ballmer P, Walshe D, Weber B, et al: Modulation of albumin synthesis in diseases of the liver and kidney. Clin Nutr 9:23, 1990 12. Blackburn G, Etter G, Mackenzie T: Criteria for choosing amino acid therapy in acute renal failure. Am J Clin Nutr 31:1841, 1978 13. Blumenkrantz M, Kopple J, Komer A, et al: Total parenteral nutrition in the management of acute renal failure. Am J Clin Nutr 31:1831, 1978 14. Bondy P, Engle F, Farror B: The metabolism of amino acids and protein in the adrenalectomized and nephrectomized rat. Endocrinology 44:174, 1949 15. Bosch J, Lew S, Glabman S, et al: Renal hemodynamic changes in humans: Response to protein loading in normal and diseased kidneys. Am J Med 81:809, 1986 16. Buzby G, Williford W, Peterson 0, et al: A randomized clinical trial of total parenteral nutrition in malnourished surgical patients: The rationale and impact of previous clinical trials and pilot study on protocol design. Am J Clin Nutr 47:357, 1988 17. Cano N, Labastic-Coeyrehouro J, Lacombe P, et al: Perdialytic parenteral nutrition with lipids and amino acids in malnourished dialysis patients. Am J Clin Nutr 52:726, 1990 18. Chanard J, Toupance 0, Gillery P, et al: Evaluation of protein loss during hemofiltration. Kidney Int 33:S114, 1988
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