Guarnieri G, Panzetta G, Toigo G (eds): Metabolic and Nutritional Abnormalities in Kidney Disease. Contrib Nephrol. Basel, Karger, 1992, vol 98, pp 183-191
Factors Affecting Nitrogen Balance in Hemodialysis Patients Giovanni Panzettaa, Francesco Bianco a, Nicola Tessitoreb, Rocco Μicciolo°
Evidence of protein malnutrition may be found in most of nutritional surveys of dialysis patients and wasting is present in 10-15 % of all patients [l-8]. Several factors have been considered responsible for protein malnutrition; however, increased protein catabolism and decreased protein intake are the major causes [9]. The enhanced protein catabolism has been usually ascribed to abnormalities in cellular metabolism secondary to hormonal disturbances [l0], accumulation of uremic toxins [11], removal of substrates during dialysis [ 12], and enhanced proteolytic activity of plasma [9]. More recently, two other factors have been identified: the blood-membrane interaction through the release of cytokines by activated leukocytes [ 13] and metabolic acidosis [9], which may be only partially corrected by dialysis (table 1). On the other hand, factors responsible for a poor nutritional intake include (table 2): uremic anorexia, intercurrent diseases and surgical therapy, dialysis-related side effects, drug assumption [ 14], psychological and social difficulties. In addition, Lindsay and Spanner [15] have recently postulated that an increase in dialysis therapy, as reflected by an increase in kt/V index, and the use of more permeable membranes could ameliorate the appetite and, hence, protein intake by the patients. Owing to both protein hypercatabolism and hampered dietary protein intake, nitrogen balance is expected to be negative in a substantial number of apparently uncomplicated dialysis patients. Indeed, short-term experi-
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aServizío di Nefrologia e Dialisi, Ospedale Maggiore, Trieste; b Divisione Clinicizzata di Nefrologia, Università degli Studi dí Verona, Verona; rIstituto dí Statistica, Università degli Study di Trento, Trento, Italia
Panetta/Bianco/Tessitore/Micciolo
184
Table 1. Causes of protein hypercatabolism Hormonal disturbances Insulin resistance Glucocorticoid, glucagon, PTH excess Uremic toxins Enhanced proteolytic activity of serum Removal of substrates during dialysis Amino acids, peptides Glucose metabolites, vitamins Blood-membrane interaction Metabolic acidosis
Table 2. Causes of decreased protein intake
mental studies have demonstrated that nitrogen balance is negative if about 1 g protein and 35 kcal/kg body weight are not provided [16, 17]. However, conventional nitrogen balance studies are complex and cannot be routinely applied to large dialysis patient populations. Moreover, these studies are based on changes in dietary regimen that might last not enough to make sure of a complete metabolic equilibration to the new level of nutrient intake, particularly if proteins or energy are very low. Therefore, it is possible that in patients long adapted to their usual low protein diets less proteins and calories are required to maintain nitrogen balance, at the expenses, however, of an abnormal nutritional status. In addition, it is also likely that, beside the nutrient intake, several other factors, such as acid-base balance, dialysis dosage or membrane, can significantly affect nitrogen metabolism in clinical practice. To try to define some of these questions we decided to study the nitrogen balance in a large group of dialysis patients. To this purpose, we did not use dietary manipulations and conventional nitrogen balance tech-
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Uremic anorexia Intercurrent diseases, surgical therapy Dialysis-related side effects Drug assumption Psychological and social factors Inadequate dialysis dose (kt/V) Membrane permeability of filters
Factors Affecting Nitrogen Balance in Hemodialysis Patients
185
niques, which are essential for optimal precision, but are unsuitable in a clinical setting. We rather studied all patients on their usual diets that contain very different amounts of proteins and calories as it is usual in every dialysis patient population and we used the fractional urea synthesis as a measure of nitrogen balance. Patients and Methods We studied 36 nondiabetic patients, 23 males and 13 females, aged 31-69 years, on treatment for 6-116 months. The primary renal disease was chronic glomerulonephritis in 12 patients, hypertensive nephrosclerosis in 9, chronic pyelonephritis in 5, polycystic kidney disease in 4, and unknown in 6 patients. All patients were dialyzed with a 4-hour, 3 times/week schedule, using either hollowfiber or parallel-flow filters with 1-1.3 m2 cuprophane membranes. Dialysate and blood flow rates were regularly controlled and maintained at 500 and 300 ml/min, respectively. The patients were selected on the basis of two main criteria: (1) stable clinical conditions in absence of systemic diseases, gastro-enteric tract disorders, infections, and intercurrent diseases, and (2) consent to participate in the study and ability to provide complete and accurate information about their nutrient intake. The study period lasted 7 days, during which a food-intake record was obtained and urea production was measured in all patients. The ideal body weight was also estimated according to patients' size class.
Urea Production All patients underwent a urea kinetic study according to the direct dialysis quantification method. Urea production (UPr) was estimated by measuring urea excretion in dialysate (D) and urine (U) and by taking into account changes in body urea pool (P) during the observation period: UPr = D + U ± P. The spent dialysate was collected in separate tanks every hour during the three hemodialysis sessions of the week. This was accomplished to allow optimal mixing of dialysis fluid and aliquots from each collection were frozen until they were analyzed in duplicate. Urine samples were acidified with hydrochloric acid and similarly preserved and analyzed in 6 patients with a daily diuresis exceeding 200 ml.
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Food-Intake Record All patients were trained by the medical staff and the dietitian assessed their dietary intakes at frequent intervals in a program of nutritional surveillance. Therefore, patients were encouraged to avoid changes in their dietary habits at the moment of the survey. Patients were provided with scales and were required to weigh the food before cooking. When necessary, precision in assessing food consumption was obtained with the weighing of plates before and after meal. The dietary intake was recorded during the entire observation period and written diaries were critically examined by the dietitian during the dialysis sessions, when patients had a fresh memory of the food ingested. From the foodintake records the average daily ingestion of nutrients was calculated using a computerized diet-analysis system (Dietalog).
Panzetta/Bianco/Tessitore/Micciolo
186
Table 3. Clinical and biochemical data of patients, protein and energy content of diets, fractional urea synthesis (ui/dl) Age, years Dialysis duration, months BUN concentration, mg/dl Plasma HCO3, mEq/1 kt/V Protein intake, g/kg Energy intake, kcal/kg uN/dN
54± 11 33 ± 30 66 ± 13 20.0± 2.5 1.05±0.20 0.98±0.23 29.0± 4.3 0.82±0.20
Changes in body urea pool (P) were calculated according to the formula: P = V (Ct—Co), where V was the urea distribution volume derived by urea kinetics [ 18], Co and Ct were plasma urea concentrations at the beginning and at the end of the study. Fractional Urea Synthesis Nitrogen balance in our patients was estimated by fractional urea synthesis, which is the ratio between urea nitrogen production and dietary nitrogen intake. It represents the fraction of ingested nitrogen which is metabolized to urea nitrogen. This parameter is a useful index of nitrogen balance [ 19-21 ] since urea generation in normal subjects is regularly equal to the 80% of dietary nitrogen when nitrogen balance is neutral [22]. In dialysis patients a negative nitrogen balance may be assumed when fractional urea synthesis exceeds 0.85 [21]. Assay Methods Urea concentration was determined enzymatically with the urease method. Predialytic acid-base status of arterial blood was evaluated with the pH-meter IL 213; plasma bicarbonate concentration was derived from pH and pCO2 using the Henderson-Hasselbach equation. Statistical Analysis We used the linear correlation analysis and the multiple correlation analysis, according to the `best fitting' model. A level of significance of at least 0.05 was always adopted.
The dietary survey in our patients demonstrated that protein and energy intakes were 0.98 ± 0.23 g/kg and 29.0 ± 4.3 kcal/kg ideal body weight, respectively (table 3).
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Results and Comment
Factors Affecting Nitrogen Balance in Hemodialysis Patients
187
1.6 1.4
3 1.2 ■
O)
■
■• ■ ■
■
■ ■
•• ■
■
■ ■
. ■
■
■ ■
•
■
■ ■
0.4 0.2 ι ι ι Ι Ι ι Ι ι ι Ι Ι ι ι ι ι 0 ~~ 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 Energy intake, kcal/kg b w
Although the mean value of nutrients might appear satisfactory, a great variability in the dietary intake was noted in individual patients. Indeed, most of our patients had an inadequate caloric intake (lower than 35 kcal/kg) and about 50% of them ingested less than 1 g protein/kg body weight. From figure 1, which shows the distribution of data with respect to the recommended intake, it is also evident that energy and protein contents were directly related in the patients' diet (r = 0.639; p < 0.01). Table 4 shows the results of the linear correlation analysis: among the different clinical parameters, only age of patients and predialytic bicarbonate concentration were significantly correlated with protein intake. As expected, both protein and energy in patients' diet were found to be inversely related with fractional urea synthesis. In particular, when protein intake fell below 0.94 g/kg, fractional urea synthesis rose over 0.85, suggesting that nitrogen balance became negative with a protein intake just below 1 g/kg body weight.
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Fig. 1. Daily caloric and protein intakes. Distribution of individual data with respect to ideal levels.
188
Panzetta /Bianco/Tessitore/Micciolo
Table 4. Linear correlation analysis between protein or energy content of diet and different clinical and biochemical parameters Proteins r Age Dialysis duration BUN Plasma bicarbonate kt/V uI/dl
—0.358 NS NS —0.363 NS —0.52
Calories r NS NS NS NS IS —0.39
p 0.05 0.05 0.01-0.05
Dependent variable
Independent variables
ui/dl
1 Proteins 2 Calories 3 kt/V 4 BUN 5 HCO3 6 Acetate/bicarbonate
ui/dl vs. 1 — 6: r = 0.699 ui/di vs. 1 + 4: r = 0.677
To better define the role of dietary and clinical factors on nitrogen balance, we submitted our data to multiple regression analysis. We considered fractional urea synthesis as the dependent variable and proteins, calories, kt/V, predialysis BUN values, plasma bicarbonate levels, and presence of acetate or bicarbonate (22 patients) in the dialysis fluid as the independent variables (table 5). We found a significant correlation between fractional urea synthesis and the six variables (r = 0.699); however, by eliminating those variables which did not reach a significant level in the regression equation, only dietary proteins (negatively) and BUN levels (positively) significantly correlated with nitrogen balance (r = 0.677). These two factors were able to explain about 50% of the total variability of nitrogen balance. Therefore, according to our data, a negative nitrogen
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Table 5. Multiple regression analysis between fractional urea synthesis (ui/dl) and six different variables (`best fitting' model procedure)
Factors Affecting Nitrogen Balance in Hemodialysis Patients
189
balance was present when both a low protein intake and a relatively higher plasma urea level were simultaneously associated. Energy intake, on the contrary, which was significantly correlated with nitrogen balance at the linear correlation analysis, lost its statistical significance when proteins and BUN levels were taken into account with the multiple regression analysis. A direct relationship between kt/V and protein catabolic rate (PCR) in dialysis patients has been recently observed by Lindsay and Spanner [ 15]. These authors postulated that the dietary protein intake, as reflected by the PCR values, was dependent upon the amount of dialysis therapy. Indeed, in their study, PCR varied according to dialysis dosage. Our data do not support this hypothesis, since both protein intake and nitrogen balance were independent of kt/V. It is important to note, however, that the minimum dialysis dose was different in the two studies: a kt/V value lower than 0.8 was occasional in our patients (3 cases), while these values were quite common in the patients studied by Lindsay and Spanner [ 15]. It is very likely, therefore, that a direct dependence of protein intake upon kt/V may be appreciated only when a more adequate treatment is prescribed to patients receiving an inadequate dialysis dose, or vice versa. It is known that acidosis stimulates muscle protein catabolism [23] and that correction of metabolic acidosis or bicarbonate hemodialysis improve nitrogen balance and body mass [23, 24]. In our study we did not find any difference in nitrogen balance between patients on acetate and those on bicarbonate hemodialysis treatment. It is to note, however, that metabolic acidosis was effectively controlled in both groups of patients.
Our study confirms the prominent role of protein intake on nitrogen metabolism in dialysis patients. About 1 g protein/kg body weight was required even in subjects long adapted to their diets. A role for energy intake was not evident in our study probably because caloric content varied in proportion to protein content in patients' diet. In our patients, whose dialysis therapy was adequate and acid-base balance correct, nitrogen metabolism was independent of kt/V, plasma bicarbonate levels and type of buffer in dialysis fluid.
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Conclusions
Panzetta/Bianco/Tessitore/Micciolo
190
l Kopple JD, Swendseid ΜΕ: Protein and amino acid metabolism in uremic patients undergoing maintenance hemodialysis. Kidney Int 1975;7(suppl 2):S64—S72. 2 Schaeffer G, Heinze V, Jontofsohn R, Katz N, Rippich TH, Schäfer B, Südhoff A, Zimmerman W, Kluthe R: Amino acid and protein intake in RDT patients. A nutritional and biochemical analysis. Clin Nephrol 1975;3:228-233. 3 Phillips ΜΕ, Havard J, Howard JP: Oral essential amino acid supplementation in patients on maintenance hemodialysis. Clin Nephrol 1978;9:241-248. 4 Klute R, Lüttgen MF, Capetianu T, Heinze V, Katz N, Südhoff A: Protein requirements in maintenance hemodialysis. Am J Clin Nutr 1978;31:1812-1820. 5 Furst P, Alvestrand A, Bergström J: Effects of nutrition and catabolic stress on intracellular amino acid pools in uremia. Am J Clin Nutr 1980;33:1387-1395. 6 Blumenkrantz MJ, Kopple JD, Gutman RA, Chan VK, Barbour GL, Roberts C, Shen VC, Tucker CT, Curtis FK, Coburn SW: Methods for assessing nutritional status of patients with renal failure. Am J Clin Nutr 1980;33:1567-1585. 7 Young GA, Swanepoel CR, Craft MR, Hobson SM, Parsons FM: Anthropometry and plasma valine, amino acids, and proteins in the nutritional assessment of hemodialysis patients. Kidney Int 1982;21:492-499. 8 Feinstein EI, Kopple JD: Severe wasting and malnutrition in a patient undergoing maintenance dialysis. Am J Nephrol 1985;5:398-405. 9 Heidland A, Schaefer RI, Heidbreder, Hörl WH: Catabolic factors in renal failure: therapeutic approaches. Nephrol Dial Transplant 1988;3:8-16. 10 Emmanouel DS, Lindheimer MD, Katz AI: Endocrine abnormalities in chronic renal failure: pathogenetic principles and clinical implications. Serif Nephrol 1981;1:151-175. 11 Cernacek P, Spustova U, Dzurik R: Inhibitor(s) of protein synthesis in uremic serum and urine: partial purification and relationship to amino acid transport. Biochem Med 1982;27:305-316. 12 Wolfson M, Jones MR, Kopple JD: Amino acid losses during hemodialysis with infusion of amino acids and glucose. Kidney Int 1982;21:500-506. 13 Gutierrez A, Aalvestrand A, Wahren J, Bergström J: Effect of in vivo contact between blood and dialysis membranes on protein catabolism in humans. Kidney Int 1990;38:487-494. 14 Kopple JD: Nutritional therapy in kidney failure. Nutr Rev 1981;39:193-206. 15 Lindsay RI, Spanner E: A hypothesis: the protein catabolic rate is dependent upon the type and amount of treatment in dialyzed uremic patients. Am J Kidney Dis 1989;13:382-389. 16 Borah MF, Schoenfeld PV, Gotch FA, Sargent JA, Wolfson M, Humphreys MH: Nitrogen balance during intermittent dialysis therapy of uremia. Kidney Int 1978; 14:491-500. 17 Slomovitz LA, Monteon FJ, Grosvenor M: Effect of energy intake on nutritional status in maintenance hemodialysis patients. Kidney Int 1989;35:704-711. 18 Lankhorst BJ, Ellis P, Nosse C, Malchesky P, Magnusson MO: A practical guide to kinetic modeling using the technique of direct dialysis quantification. Dial Transplant 1983;12:694-706.
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References
Factors Affecting Nitrogen Balance in Hemodialysis Patients
191
Dr. G. Panzetta, Servizio di Nefrologia e Dialisi, Ospedale Maggiore, I-34125 Trieste (Italy)
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19 Abitbol CL, Holliday MA: The effect of energy and nitrogen intake upon urea production in children with uremia and undernutrition. Clin Nephrol 1978;10:9-15. 20 Abitbol C, Jean G, Broyer M: Urea synthesis in moderate experimental uremia. Kidney Int 1981;19:648-653. 21 Arisi L: Nutritional status and nitrogen metabolism in patients treated with short dialysis; in Cambi V (eds): Short Dialysis. Boston, Nijhoff, 1987, pp 149-163. 22 Marini BJ, Steinman TI, Mitch WE: A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int 1985;27:58-65. 23 Seyffart G, Ensminger A, Scholz R: Increase of body mass during long-term bicarbonate hemodialysis. Kidney Int 1987; 32(supp122):S174-5177. 24 Papadoyannakis NJ, Stefanidis CJ, Patricarea A, Kotsovasilis K, Georgiopoulou A: The effect of calcium carbonate administration on nitrogen metabolism in patients on hemodialysis. Proc EDTA-ERA 1985;22:83-87.
Factors Affecting Nitrogen Balance in Hemodialysis Patients Giovanni Panzettaa, Francesco Bianco a, Nicola Tessitoreb, Rocco Μicciolo°
Evidence of protein malnutrition may be found in most of nutritional surveys of dialysis patients and wasting is present in 10-15 % of all patients [l-8]. Several factors have been considered responsible for protein malnutrition; however, increased protein catabolism and decreased protein intake are the major causes [9]. The enhanced protein catabolism has been usually ascribed to abnormalities in cellular metabolism secondary to hormonal disturbances [l0], accumulation of uremic toxins [11], removal of substrates during dialysis [ 12], and enhanced proteolytic activity of plasma [9]. More recently, two other factors have been identified: the blood-membrane interaction through the release of cytokines by activated leukocytes [ 13] and metabolic acidosis [9], which may be only partially corrected by dialysis (table 1). On the other hand, factors responsible for a poor nutritional intake include (table 2): uremic anorexia, intercurrent diseases and surgical therapy, dialysis-related side effects, drug assumption [ 14], psychological and social difficulties. In addition, Lindsay and Spanner [15] have recently postulated that an increase in dialysis therapy, as reflected by an increase in kt/V index, and the use of more permeable membranes could ameliorate the appetite and, hence, protein intake by the patients. Owing to both protein hypercatabolism and hampered dietary protein intake, nitrogen balance is expected to be negative in a substantial number of apparently uncomplicated dialysis patients. Indeed, short-term experi-
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
aServizío di Nefrologia e Dialisi, Ospedale Maggiore, Trieste; b Divisione Clinicizzata di Nefrologia, Università degli Studi dí Verona, Verona; rIstituto dí Statistica, Università degli Study di Trento, Trento, Italia
Panetta/Bianco/Tessitore/Micciolo
184
Table 1. Causes of protein hypercatabolism Hormonal disturbances Insulin resistance Glucocorticoid, glucagon, PTH excess Uremic toxins Enhanced proteolytic activity of serum Removal of substrates during dialysis Amino acids, peptides Glucose metabolites, vitamins Blood-membrane interaction Metabolic acidosis
Table 2. Causes of decreased protein intake
mental studies have demonstrated that nitrogen balance is negative if about 1 g protein and 35 kcal/kg body weight are not provided [16, 17]. However, conventional nitrogen balance studies are complex and cannot be routinely applied to large dialysis patient populations. Moreover, these studies are based on changes in dietary regimen that might last not enough to make sure of a complete metabolic equilibration to the new level of nutrient intake, particularly if proteins or energy are very low. Therefore, it is possible that in patients long adapted to their usual low protein diets less proteins and calories are required to maintain nitrogen balance, at the expenses, however, of an abnormal nutritional status. In addition, it is also likely that, beside the nutrient intake, several other factors, such as acid-base balance, dialysis dosage or membrane, can significantly affect nitrogen metabolism in clinical practice. To try to define some of these questions we decided to study the nitrogen balance in a large group of dialysis patients. To this purpose, we did not use dietary manipulations and conventional nitrogen balance tech-
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Uremic anorexia Intercurrent diseases, surgical therapy Dialysis-related side effects Drug assumption Psychological and social factors Inadequate dialysis dose (kt/V) Membrane permeability of filters
Factors Affecting Nitrogen Balance in Hemodialysis Patients
185
niques, which are essential for optimal precision, but are unsuitable in a clinical setting. We rather studied all patients on their usual diets that contain very different amounts of proteins and calories as it is usual in every dialysis patient population and we used the fractional urea synthesis as a measure of nitrogen balance. Patients and Methods We studied 36 nondiabetic patients, 23 males and 13 females, aged 31-69 years, on treatment for 6-116 months. The primary renal disease was chronic glomerulonephritis in 12 patients, hypertensive nephrosclerosis in 9, chronic pyelonephritis in 5, polycystic kidney disease in 4, and unknown in 6 patients. All patients were dialyzed with a 4-hour, 3 times/week schedule, using either hollowfiber or parallel-flow filters with 1-1.3 m2 cuprophane membranes. Dialysate and blood flow rates were regularly controlled and maintained at 500 and 300 ml/min, respectively. The patients were selected on the basis of two main criteria: (1) stable clinical conditions in absence of systemic diseases, gastro-enteric tract disorders, infections, and intercurrent diseases, and (2) consent to participate in the study and ability to provide complete and accurate information about their nutrient intake. The study period lasted 7 days, during which a food-intake record was obtained and urea production was measured in all patients. The ideal body weight was also estimated according to patients' size class.
Urea Production All patients underwent a urea kinetic study according to the direct dialysis quantification method. Urea production (UPr) was estimated by measuring urea excretion in dialysate (D) and urine (U) and by taking into account changes in body urea pool (P) during the observation period: UPr = D + U ± P. The spent dialysate was collected in separate tanks every hour during the three hemodialysis sessions of the week. This was accomplished to allow optimal mixing of dialysis fluid and aliquots from each collection were frozen until they were analyzed in duplicate. Urine samples were acidified with hydrochloric acid and similarly preserved and analyzed in 6 patients with a daily diuresis exceeding 200 ml.
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Food-Intake Record All patients were trained by the medical staff and the dietitian assessed their dietary intakes at frequent intervals in a program of nutritional surveillance. Therefore, patients were encouraged to avoid changes in their dietary habits at the moment of the survey. Patients were provided with scales and were required to weigh the food before cooking. When necessary, precision in assessing food consumption was obtained with the weighing of plates before and after meal. The dietary intake was recorded during the entire observation period and written diaries were critically examined by the dietitian during the dialysis sessions, when patients had a fresh memory of the food ingested. From the foodintake records the average daily ingestion of nutrients was calculated using a computerized diet-analysis system (Dietalog).
Panzetta/Bianco/Tessitore/Micciolo
186
Table 3. Clinical and biochemical data of patients, protein and energy content of diets, fractional urea synthesis (ui/dl) Age, years Dialysis duration, months BUN concentration, mg/dl Plasma HCO3, mEq/1 kt/V Protein intake, g/kg Energy intake, kcal/kg uN/dN
54± 11 33 ± 30 66 ± 13 20.0± 2.5 1.05±0.20 0.98±0.23 29.0± 4.3 0.82±0.20
Changes in body urea pool (P) were calculated according to the formula: P = V (Ct—Co), where V was the urea distribution volume derived by urea kinetics [ 18], Co and Ct were plasma urea concentrations at the beginning and at the end of the study. Fractional Urea Synthesis Nitrogen balance in our patients was estimated by fractional urea synthesis, which is the ratio between urea nitrogen production and dietary nitrogen intake. It represents the fraction of ingested nitrogen which is metabolized to urea nitrogen. This parameter is a useful index of nitrogen balance [ 19-21 ] since urea generation in normal subjects is regularly equal to the 80% of dietary nitrogen when nitrogen balance is neutral [22]. In dialysis patients a negative nitrogen balance may be assumed when fractional urea synthesis exceeds 0.85 [21]. Assay Methods Urea concentration was determined enzymatically with the urease method. Predialytic acid-base status of arterial blood was evaluated with the pH-meter IL 213; plasma bicarbonate concentration was derived from pH and pCO2 using the Henderson-Hasselbach equation. Statistical Analysis We used the linear correlation analysis and the multiple correlation analysis, according to the `best fitting' model. A level of significance of at least 0.05 was always adopted.
The dietary survey in our patients demonstrated that protein and energy intakes were 0.98 ± 0.23 g/kg and 29.0 ± 4.3 kcal/kg ideal body weight, respectively (table 3).
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Results and Comment
Factors Affecting Nitrogen Balance in Hemodialysis Patients
187
1.6 1.4
3 1.2 ■
O)
■
■• ■ ■
■
■ ■
•• ■
■
■ ■
. ■
■
■ ■
•
■
■ ■
0.4 0.2 ι ι ι Ι Ι ι Ι ι ι Ι Ι ι ι ι ι 0 ~~ 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 Energy intake, kcal/kg b w
Although the mean value of nutrients might appear satisfactory, a great variability in the dietary intake was noted in individual patients. Indeed, most of our patients had an inadequate caloric intake (lower than 35 kcal/kg) and about 50% of them ingested less than 1 g protein/kg body weight. From figure 1, which shows the distribution of data with respect to the recommended intake, it is also evident that energy and protein contents were directly related in the patients' diet (r = 0.639; p < 0.01). Table 4 shows the results of the linear correlation analysis: among the different clinical parameters, only age of patients and predialytic bicarbonate concentration were significantly correlated with protein intake. As expected, both protein and energy in patients' diet were found to be inversely related with fractional urea synthesis. In particular, when protein intake fell below 0.94 g/kg, fractional urea synthesis rose over 0.85, suggesting that nitrogen balance became negative with a protein intake just below 1 g/kg body weight.
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Fig. 1. Daily caloric and protein intakes. Distribution of individual data with respect to ideal levels.
188
Panzetta /Bianco/Tessitore/Micciolo
Table 4. Linear correlation analysis between protein or energy content of diet and different clinical and biochemical parameters Proteins r Age Dialysis duration BUN Plasma bicarbonate kt/V uI/dl
—0.358 NS NS —0.363 NS —0.52
Calories r NS NS NS NS IS —0.39
p 0.05 0.05 0.01-0.05
Dependent variable
Independent variables
ui/dl
1 Proteins 2 Calories 3 kt/V 4 BUN 5 HCO3 6 Acetate/bicarbonate
ui/dl vs. 1 — 6: r = 0.699 ui/di vs. 1 + 4: r = 0.677
To better define the role of dietary and clinical factors on nitrogen balance, we submitted our data to multiple regression analysis. We considered fractional urea synthesis as the dependent variable and proteins, calories, kt/V, predialysis BUN values, plasma bicarbonate levels, and presence of acetate or bicarbonate (22 patients) in the dialysis fluid as the independent variables (table 5). We found a significant correlation between fractional urea synthesis and the six variables (r = 0.699); however, by eliminating those variables which did not reach a significant level in the regression equation, only dietary proteins (negatively) and BUN levels (positively) significantly correlated with nitrogen balance (r = 0.677). These two factors were able to explain about 50% of the total variability of nitrogen balance. Therefore, according to our data, a negative nitrogen
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Table 5. Multiple regression analysis between fractional urea synthesis (ui/dl) and six different variables (`best fitting' model procedure)
Factors Affecting Nitrogen Balance in Hemodialysis Patients
189
balance was present when both a low protein intake and a relatively higher plasma urea level were simultaneously associated. Energy intake, on the contrary, which was significantly correlated with nitrogen balance at the linear correlation analysis, lost its statistical significance when proteins and BUN levels were taken into account with the multiple regression analysis. A direct relationship between kt/V and protein catabolic rate (PCR) in dialysis patients has been recently observed by Lindsay and Spanner [ 15]. These authors postulated that the dietary protein intake, as reflected by the PCR values, was dependent upon the amount of dialysis therapy. Indeed, in their study, PCR varied according to dialysis dosage. Our data do not support this hypothesis, since both protein intake and nitrogen balance were independent of kt/V. It is important to note, however, that the minimum dialysis dose was different in the two studies: a kt/V value lower than 0.8 was occasional in our patients (3 cases), while these values were quite common in the patients studied by Lindsay and Spanner [ 15]. It is very likely, therefore, that a direct dependence of protein intake upon kt/V may be appreciated only when a more adequate treatment is prescribed to patients receiving an inadequate dialysis dose, or vice versa. It is known that acidosis stimulates muscle protein catabolism [23] and that correction of metabolic acidosis or bicarbonate hemodialysis improve nitrogen balance and body mass [23, 24]. In our study we did not find any difference in nitrogen balance between patients on acetate and those on bicarbonate hemodialysis treatment. It is to note, however, that metabolic acidosis was effectively controlled in both groups of patients.
Our study confirms the prominent role of protein intake on nitrogen metabolism in dialysis patients. About 1 g protein/kg body weight was required even in subjects long adapted to their diets. A role for energy intake was not evident in our study probably because caloric content varied in proportion to protein content in patients' diet. In our patients, whose dialysis therapy was adequate and acid-base balance correct, nitrogen metabolism was independent of kt/V, plasma bicarbonate levels and type of buffer in dialysis fluid.
Downloaded by: Université de Paris 193.51.85.197 - 2/10/2020 12:36:00 PM
Conclusions
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References
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