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Calciuretic response to protein loading in burn patients
198 8urns.6. 198-201
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Calciuretic response to protein loading in burn patients A. November-Dusansky,
J. A. Moylan, H. Linkswiler and C. Elson
Departments of Nutritional Sciences and Surgery, University of Wisconsin, Madison, Duke University Medical Center, Durham, N. Carolina
Summary
The effect of dietary protein on calcium excretion has been evaluated in 6 patients with major bums. A marked calciuresis was noted when patients received more than 150 g protein per day while urinary calciums approaching normal levels were noted when protein intake was less than 150 g. Excessive calcium mobilization and excretion secondary to protein loading may account for heterotopic calcium deposits and renal stones frequently seen in bum patients.
Although the mechanism is not clearly defined, a primary alteration in calcium transport by the kidney seems likely. INTRODUCTION FOLLOWING
severe thermal injury, patients exhibit negative nitrogen balance, weight loss, increased heat production and disturbed carbohydrate metabolism (Kinney, 1967). Depending on the severity of the injury, resting oxygen demand (Kinney et al., 1970a) and nitrogen excretion (Kinney, 1960) are increased from 40 to 100 per cent above normal. Following the initial stabilization, nutritional support is directed towards the replacement and supplementation of those nutrients required in the healing process. Until recently, the extensive nitrogen loss was thought to reflect an adaptive response to the patient’s increased energy expenditure (Moore, 1959). It is now recognized that increased nitrogen metabolism develops concomitantly with the derangement of carbohydrate metabolism which elicits an increased flow of intermediates towards glucose (Duke et al., 1970; Kinney et al., 1970a, b).
Kinney et al. (1970a) discussed a number of alternative mechanisms for this response. For the thermally injured patient, the antagonism of the catecholamines (Hinton et al., 1971) and adrenal corticoids (Howard, 1955) to insulin action appears to be operative. Although the energy contribution of protein to the patients’ calorie expenditure does not rise above 15 to 20 per cent (Kinney et al., 1970a), nutrient supplementation often incorporates higher levels of protein. Recent reports from Linkswiler’s laboratory (Johnson et al., 1970; Walker and Linkswiler, 1972; Anand and Linkswiler, 1974; Linkswiler et al., 1974) and Margen’s laboratory (Margen et al. 1974) demonstrate that levels of protein similar to those given to bum patients exert an adverse effect on the calcium balance of adult males. The additive effects of trauma, bedrest and excessive nitrogen loading may cause an increase in calcium mobilization, negative calcium balance and many side-effects including extra-osseous calcium deposits and renal stones. The bum patient is subjected to external and internal forces, e.g. immobilization, stress and endocrine imbalance, that cannot be modified to reduce bone calcium mobilization and urinary calcium excretion. However, dietary modifrcation of protein, energy and calcium intakes might be manipulated to reduce the complications of excessive calcium mobilization. In this report, the individual calciuretic responses of 6 burn patients to dietary modifrcations of protein intakes and intravenous albumin administration are recorded.
November-Dusansky
199
et al.: Calciuretic Response to Protein Loading
Tab/e/. Six male patients with burns averaging
Age
Admission weight kg)
50%
Burn % body
surface
Patient
(vr)
Degree
1
31
60.2
76
3rd
2 3
34 22
86.0 76.9
4
33
87.9
37 34 6 40
5
27
100.3
49
2nd 2nd 3rd 2nd and 3rd 1 stand
Convalescence period (d) 102 23 20 17
Disposition Transferred grafting Discharged Discharged
19
Transferred Grafting Discharged
36
-
for home home for home
2nd 6
52
82.2
57.5
PATIENTS AND METHODS
Selected patients with major thermal injuries admitted to the University of Wisconsin Bum Center were evaluated. Following the initial stabilization period, nitrogen and calcium studies were evaluated for a minimum of 15 days. All patients were enterally fed by regular diets with supplementary high protein and high calorie drinks. Total intakes and outputs as well as daily weights were recorded for all patients. Laboratory studies included haematocrit, white blood cell counts, blood sugars, serum albumin and total calciums as well as 24-h urinary calciums. The dietary protein and calorie load as well as intravenous albumin replacement was regulated by the attending physician’s discretion based on clinical indications.
2nd and 3rd
average (> and < 150 g/day). On protein intakes averaging 188 g/day (high) urinary calcium excretions of 551 mg/day were noted (32 observations). With protein administration of 102 g/day (low) urinary calcium levels of 238 mg/day were recorded (Fig. 1) (29 observations). Urinary output averaged 2258 cc/day during the hospitalization of these patients. Twentyfour-hour urine volumes of 18 14 cc on the high protein diet and 1948 cc on the low protein diet were noted. Serum albumin levels were maintained at 2.8 g per cent on the average during the study period. Three patients required periodic i.v. albumin supplementation to achieve these levels. Serum calcium levels during the same period averaged 8.5 mg per cent.
RESULTS
DISCUSSION
Six male patients with bum injuries averaging 50 per cent of the body surface area (range 37-76 per cent) are the basis of this report (Table I). All patients but one (52 years old) were less than 35 years of age. Hospitalization for complete healing averaged 37 days with a range of 17 to 100 days. Body weight was stabilized and maintained with a vigorous enteral diet. Average loss was less than 2 per cent of their initial admission weight (range l-3 per cent). Intakes averaged 3675 calories per day during the study period with 2760 calories being the lowest average intake and 4900 calories the maximum. Patients did not receive any calcium supplementation except that which was incorporated into the diet 1.35 g/day (1.0-1.7 g). Protein intakes are divided into high and
Trauma and prolonged bedrest have been shown to increase mobilization of calcium from bone with a resultant calciuresis. Iatrogenic aggravation of this complication could lead to increased morbidity and mortality for the injured patient. Since protein loading has been shown to increase calcium excretion in normal volunteers and many have advocated high protein administration for burn patients, we have studied the effect of protein in the diet on urinary calcium excretion. Normal urinary calcium excretion of less than 150 mg/day and greater than 200 mg/day is considered lithogenic (Willis, 196 1). Recommended daily calcium supplements for parenterally fed patients vary from 97 to 270 mgday (Lutwak, 1974) and up to 800 mg of oral calcium for
200
Burns Vol. ~/NO. 3
Low
High
600
700 3
600
0
take I\
?? Albumin - ur1~nary
intokedz50 colcum - 2002
5
z
u 4002 :
300-
5 s 2
-15oi & -lOOE
zoo-
Fig. 2. Effect of albumin intake on calcium excretion.
Fig. 1. Protein intake (g/24 h, unshaded) and calcium excretion (mg/24 h, shaded) in low and high protein diets.
enteral supported patients. While most hospital diets and commercially available products provide up to this amount of calcium, absorption of this element in seriously burned individuals is extremely variable and dietary intolerance is evidenced by significant diarrhoea is clinically common in bum patients fed on high carbohydrate diets. Both of these variables if combined with increased calciuresis could result in a significant negative calcium balance. Complications of calcium mobilization have been frequently reported in bum patients including heterotopic calcium deposits, osteoporosis and renal stones. Acute shifts in ionized calcium have been associated with coagulation abnormalities and cardiac dysarrhythmias. On an average protein intake (< 150 g/day), urinary calcium was slightly over 230 mg per day. With higher protein diets (450 g/day) there was a two and one-half fold increase in calcium excretion. While calcium balance studies were not directly performed during this evaluation, the additional calcium ingested on a high protein diet as compared to the normal protein intake was not sufficient to account for the two and one-half increase in urinary calcium. Furthermore, administration of salt-poor albumin, which is essentially calcium-free, was associated with a dramatic increase in calcium
excretion (Fig. 2) indicating a relationship between protein ingestion and calciuresis. No calcium-related complication was noted in this series although the study period was not of sufficient duration for long term complications to develop, i.e. extra-osseous deposits and renal stones. However, recently a high incidence of ankylosis and intra-articular calcification of the elbow joint occurring in bum patients receiving up to 300 g/day of dietary protein was reported. The exact mechanism of the calciuretic effect of high protein intake is not clear. Possibilities, include: (a) increase filtered load of calcium; (b) lowered parathyroid hormone (PTH) resulting in increased urinary calcium; (c) a block in phosphorus excretion; and (d) a primary block ofcalcium reabsorption in the distal tubules. The primary mechanism of an increase in the filtered load of calcium would be an increase in glomerular filtration rate. Direct measurements of GFR were not made during this study. However, the daily urinary volumes were similar (1948 v. 18 14) for both the normal and high protein loads, making this mechanism unlikely. Unpublished data from our laboratory concerning parathyroid levels and phosphorus excretion in burn and injury patients reveal similar serial PTH levels on both high and low protein diets. There was also not a primary block of phosphorus excretion since daily phosphorus excretion was higher, not lower on a high protein regimen (Schenk and Moylan, 1970). The exact mechanism of hypercalciuresis in bum patients receiving high nitrogen administration is not clearly defined but appears to be due to a primary alteration in calcium transport by the kidney rather than a secondary alteration
November-Dusansky
et al.: Calciuretic Response to Protein Loading
in calcium homeostasis since the first three aetiologies seem unlikely; however, further work must be performed.
REFERENCES Anand C. and Linkswiler H. (1974) Effect of protein intake on calcium balance of young men given 500 mg calcium daily. J. Nutr. 104,695. Duke J. H., Jorgensen S. B., Bore11 J. R. et al. (1970) Contribution of protein to caloric expenditure following injury. Surgery 68, 168. Hinton P., Allison S., Littlejohn S. et al. (1971) Insulin and glucose to reduce catabolic response to injury in burned patients. Lance1 1,767. Howard J. M. (1955) Studies of the absorption and metabolism of glucose following injury. Ann. Surg. 141,321. Johnson N., Alcantara E. and Linkswiler H. (1970) Effect of level of protein intake on urinary and fecal calcium and calcium retention of young adult males. J. Nutr. 100, 1425. Kinney J. (1960) A consideration of energy exchange in human trauma. Bull. NY Acad. Med. 36,6 17. Kinney J. (1967) The effect of injury on metabolism. Br. J. Surg. (Suppl.) 54,435.
Kinney J. M., Long C. L. and Duke J. H. (1970a) Carbohydrate and nitrogen metabolism after injury.
RCFP.SE /or rcpnnl~ 27710, USA.
vhou/dk
addressed
201
In: Porter R. and Knight J. (ed.) Ciba Foundation on in Trauma. London, Churchill, pp. 103-126. Kinney J. M., Long C. L. and Duke J. H. jun. (1970b) Energy demands in the surgical patient. In: Fox C. L. jun. and Nahas G. G. (ed.) Body Fluid Replacement in the Surgical Patient. New York, Grune and Stratton, pp. 296-300. Linkswiler H.. Jovce C. and Anand C. (1974) Calcium retention of young adult males as affected by level of protein and of calcium intake. Trans. NY Acad. Sci. Energy Metabolism
36,333.
Lutwak L. (I 974) Continuing need for dietary calcium. Geriatrics 29, I7 I. Margen S., Chu J. Y., Kaufman N. et al. (1974) The calciuretic effect of dietarv_ .orotein. Am. J. Clin. Nutr. 27, 584.
Moore. F. D. (1959) Metabolic Care of the Suraical Patient. Philadelphia, Saunders, Chapt. 4, p. 94: Schenk W. G. and Movlan J. A. (1979) Hvoercalciuresis in trauma patients. J. Traima 19,227. Walker R. and Linkswiler H. (1972) Calcium retention in the adult human male as affected by protein intake. J. Nutr. 102, 1297. Willis J. B. (1961) Determination of calcium and magnesium in urine by atomic absorption spectroscopy. Anal. Chem. 33,556. Paper accepted 1 February 1979.
10: Dr J. A. Moylan, Box 3043, Duke University Medical Center, Durham, N. Carolma
PrintedinGreatBritain
Calciuretic response to protein loading in burn patients A. November-Dusansky,
J. A. Moylan, H. Linkswiler and C. Elson
Departments of Nutritional Sciences and Surgery, University of Wisconsin, Madison, Duke University Medical Center, Durham, N. Carolina
Summary
The effect of dietary protein on calcium excretion has been evaluated in 6 patients with major bums. A marked calciuresis was noted when patients received more than 150 g protein per day while urinary calciums approaching normal levels were noted when protein intake was less than 150 g. Excessive calcium mobilization and excretion secondary to protein loading may account for heterotopic calcium deposits and renal stones frequently seen in bum patients.
Although the mechanism is not clearly defined, a primary alteration in calcium transport by the kidney seems likely. INTRODUCTION FOLLOWING
severe thermal injury, patients exhibit negative nitrogen balance, weight loss, increased heat production and disturbed carbohydrate metabolism (Kinney, 1967). Depending on the severity of the injury, resting oxygen demand (Kinney et al., 1970a) and nitrogen excretion (Kinney, 1960) are increased from 40 to 100 per cent above normal. Following the initial stabilization, nutritional support is directed towards the replacement and supplementation of those nutrients required in the healing process. Until recently, the extensive nitrogen loss was thought to reflect an adaptive response to the patient’s increased energy expenditure (Moore, 1959). It is now recognized that increased nitrogen metabolism develops concomitantly with the derangement of carbohydrate metabolism which elicits an increased flow of intermediates towards glucose (Duke et al., 1970; Kinney et al., 1970a, b).
Kinney et al. (1970a) discussed a number of alternative mechanisms for this response. For the thermally injured patient, the antagonism of the catecholamines (Hinton et al., 1971) and adrenal corticoids (Howard, 1955) to insulin action appears to be operative. Although the energy contribution of protein to the patients’ calorie expenditure does not rise above 15 to 20 per cent (Kinney et al., 1970a), nutrient supplementation often incorporates higher levels of protein. Recent reports from Linkswiler’s laboratory (Johnson et al., 1970; Walker and Linkswiler, 1972; Anand and Linkswiler, 1974; Linkswiler et al., 1974) and Margen’s laboratory (Margen et al. 1974) demonstrate that levels of protein similar to those given to bum patients exert an adverse effect on the calcium balance of adult males. The additive effects of trauma, bedrest and excessive nitrogen loading may cause an increase in calcium mobilization, negative calcium balance and many side-effects including extra-osseous calcium deposits and renal stones. The bum patient is subjected to external and internal forces, e.g. immobilization, stress and endocrine imbalance, that cannot be modified to reduce bone calcium mobilization and urinary calcium excretion. However, dietary modifrcation of protein, energy and calcium intakes might be manipulated to reduce the complications of excessive calcium mobilization. In this report, the individual calciuretic responses of 6 burn patients to dietary modifrcations of protein intakes and intravenous albumin administration are recorded.
November-Dusansky
199
et al.: Calciuretic Response to Protein Loading
Tab/e/. Six male patients with burns averaging
Age
Admission weight kg)
50%
Burn % body
surface
Patient
(vr)
Degree
1
31
60.2
76
3rd
2 3
34 22
86.0 76.9
4
33
87.9
37 34 6 40
5
27
100.3
49
2nd 2nd 3rd 2nd and 3rd 1 stand
Convalescence period (d) 102 23 20 17
Disposition Transferred grafting Discharged Discharged
19
Transferred Grafting Discharged
36
-
for home home for home
2nd 6
52
82.2
57.5
PATIENTS AND METHODS
Selected patients with major thermal injuries admitted to the University of Wisconsin Bum Center were evaluated. Following the initial stabilization period, nitrogen and calcium studies were evaluated for a minimum of 15 days. All patients were enterally fed by regular diets with supplementary high protein and high calorie drinks. Total intakes and outputs as well as daily weights were recorded for all patients. Laboratory studies included haematocrit, white blood cell counts, blood sugars, serum albumin and total calciums as well as 24-h urinary calciums. The dietary protein and calorie load as well as intravenous albumin replacement was regulated by the attending physician’s discretion based on clinical indications.
2nd and 3rd
average (> and < 150 g/day). On protein intakes averaging 188 g/day (high) urinary calcium excretions of 551 mg/day were noted (32 observations). With protein administration of 102 g/day (low) urinary calcium levels of 238 mg/day were recorded (Fig. 1) (29 observations). Urinary output averaged 2258 cc/day during the hospitalization of these patients. Twentyfour-hour urine volumes of 18 14 cc on the high protein diet and 1948 cc on the low protein diet were noted. Serum albumin levels were maintained at 2.8 g per cent on the average during the study period. Three patients required periodic i.v. albumin supplementation to achieve these levels. Serum calcium levels during the same period averaged 8.5 mg per cent.
RESULTS
DISCUSSION
Six male patients with bum injuries averaging 50 per cent of the body surface area (range 37-76 per cent) are the basis of this report (Table I). All patients but one (52 years old) were less than 35 years of age. Hospitalization for complete healing averaged 37 days with a range of 17 to 100 days. Body weight was stabilized and maintained with a vigorous enteral diet. Average loss was less than 2 per cent of their initial admission weight (range l-3 per cent). Intakes averaged 3675 calories per day during the study period with 2760 calories being the lowest average intake and 4900 calories the maximum. Patients did not receive any calcium supplementation except that which was incorporated into the diet 1.35 g/day (1.0-1.7 g). Protein intakes are divided into high and
Trauma and prolonged bedrest have been shown to increase mobilization of calcium from bone with a resultant calciuresis. Iatrogenic aggravation of this complication could lead to increased morbidity and mortality for the injured patient. Since protein loading has been shown to increase calcium excretion in normal volunteers and many have advocated high protein administration for burn patients, we have studied the effect of protein in the diet on urinary calcium excretion. Normal urinary calcium excretion of less than 150 mg/day and greater than 200 mg/day is considered lithogenic (Willis, 196 1). Recommended daily calcium supplements for parenterally fed patients vary from 97 to 270 mgday (Lutwak, 1974) and up to 800 mg of oral calcium for
200
Burns Vol. ~/NO. 3
Low
High
600
700 3
600
0
take I\
?? Albumin - ur1~nary
intokedz50 colcum - 2002
5
z
u 4002 :
300-
5 s 2
-15oi & -lOOE
zoo-
Fig. 2. Effect of albumin intake on calcium excretion.
Fig. 1. Protein intake (g/24 h, unshaded) and calcium excretion (mg/24 h, shaded) in low and high protein diets.
enteral supported patients. While most hospital diets and commercially available products provide up to this amount of calcium, absorption of this element in seriously burned individuals is extremely variable and dietary intolerance is evidenced by significant diarrhoea is clinically common in bum patients fed on high carbohydrate diets. Both of these variables if combined with increased calciuresis could result in a significant negative calcium balance. Complications of calcium mobilization have been frequently reported in bum patients including heterotopic calcium deposits, osteoporosis and renal stones. Acute shifts in ionized calcium have been associated with coagulation abnormalities and cardiac dysarrhythmias. On an average protein intake (< 150 g/day), urinary calcium was slightly over 230 mg per day. With higher protein diets (450 g/day) there was a two and one-half fold increase in calcium excretion. While calcium balance studies were not directly performed during this evaluation, the additional calcium ingested on a high protein diet as compared to the normal protein intake was not sufficient to account for the two and one-half increase in urinary calcium. Furthermore, administration of salt-poor albumin, which is essentially calcium-free, was associated with a dramatic increase in calcium
excretion (Fig. 2) indicating a relationship between protein ingestion and calciuresis. No calcium-related complication was noted in this series although the study period was not of sufficient duration for long term complications to develop, i.e. extra-osseous deposits and renal stones. However, recently a high incidence of ankylosis and intra-articular calcification of the elbow joint occurring in bum patients receiving up to 300 g/day of dietary protein was reported. The exact mechanism of the calciuretic effect of high protein intake is not clear. Possibilities, include: (a) increase filtered load of calcium; (b) lowered parathyroid hormone (PTH) resulting in increased urinary calcium; (c) a block in phosphorus excretion; and (d) a primary block ofcalcium reabsorption in the distal tubules. The primary mechanism of an increase in the filtered load of calcium would be an increase in glomerular filtration rate. Direct measurements of GFR were not made during this study. However, the daily urinary volumes were similar (1948 v. 18 14) for both the normal and high protein loads, making this mechanism unlikely. Unpublished data from our laboratory concerning parathyroid levels and phosphorus excretion in burn and injury patients reveal similar serial PTH levels on both high and low protein diets. There was also not a primary block of phosphorus excretion since daily phosphorus excretion was higher, not lower on a high protein regimen (Schenk and Moylan, 1970). The exact mechanism of hypercalciuresis in bum patients receiving high nitrogen administration is not clearly defined but appears to be due to a primary alteration in calcium transport by the kidney rather than a secondary alteration
November-Dusansky
et al.: Calciuretic Response to Protein Loading
in calcium homeostasis since the first three aetiologies seem unlikely; however, further work must be performed.
REFERENCES Anand C. and Linkswiler H. (1974) Effect of protein intake on calcium balance of young men given 500 mg calcium daily. J. Nutr. 104,695. Duke J. H., Jorgensen S. B., Bore11 J. R. et al. (1970) Contribution of protein to caloric expenditure following injury. Surgery 68, 168. Hinton P., Allison S., Littlejohn S. et al. (1971) Insulin and glucose to reduce catabolic response to injury in burned patients. Lance1 1,767. Howard J. M. (1955) Studies of the absorption and metabolism of glucose following injury. Ann. Surg. 141,321. Johnson N., Alcantara E. and Linkswiler H. (1970) Effect of level of protein intake on urinary and fecal calcium and calcium retention of young adult males. J. Nutr. 100, 1425. Kinney J. (1960) A consideration of energy exchange in human trauma. Bull. NY Acad. Med. 36,6 17. Kinney J. (1967) The effect of injury on metabolism. Br. J. Surg. (Suppl.) 54,435.
Kinney J. M., Long C. L. and Duke J. H. (1970a) Carbohydrate and nitrogen metabolism after injury.
RCFP.SE /or rcpnnl~ 27710, USA.
vhou/dk
addressed
201
In: Porter R. and Knight J. (ed.) Ciba Foundation on in Trauma. London, Churchill, pp. 103-126. Kinney J. M., Long C. L. and Duke J. H. jun. (1970b) Energy demands in the surgical patient. In: Fox C. L. jun. and Nahas G. G. (ed.) Body Fluid Replacement in the Surgical Patient. New York, Grune and Stratton, pp. 296-300. Linkswiler H.. Jovce C. and Anand C. (1974) Calcium retention of young adult males as affected by level of protein and of calcium intake. Trans. NY Acad. Sci. Energy Metabolism
36,333.
Lutwak L. (I 974) Continuing need for dietary calcium. Geriatrics 29, I7 I. Margen S., Chu J. Y., Kaufman N. et al. (1974) The calciuretic effect of dietarv_ .orotein. Am. J. Clin. Nutr. 27, 584.
Moore. F. D. (1959) Metabolic Care of the Suraical Patient. Philadelphia, Saunders, Chapt. 4, p. 94: Schenk W. G. and Movlan J. A. (1979) Hvoercalciuresis in trauma patients. J. Traima 19,227. Walker R. and Linkswiler H. (1972) Calcium retention in the adult human male as affected by protein intake. J. Nutr. 102, 1297. Willis J. B. (1961) Determination of calcium and magnesium in urine by atomic absorption spectroscopy. Anal. Chem. 33,556. Paper accepted 1 February 1979.
10: Dr J. A. Moylan, Box 3043, Duke University Medical Center, Durham, N. Carolma