Urinary Urea Excretion Research Articles

Effects of growth hormone (GH) administration on functional hepatic nitrogen clearance: studies in normal subjects and GH-deficient patients.

A decline in serum urea levels and urinary urea excretion is usually seen after GH administration in humans, indicating overall protein anabolism. Whether this reflects the diminished supply of alpha-amino acids for urea synthesis or a substrate-independent hepatic mechanism is unknown. To pursue this we measured the urea nitrogen synthesis rate (UNSR) and blood alanine levels before, during, and after a 4-h constant iv infusion of alanine (2 mmol/kg BW.h). UNSR was estimated hourly as urinary excretion corrected for gut hydrolysis and accumulation in total body water. The slope of the linear relationship between UNSR and circulating alanine levels represents the hepatic components of conversion of amino nitrogen and is denoted the functional hepatic nitrogen clearance (FHNC). Eight male volunteers were randomly investigated on three occasions: 1) after 12-h iv saline infusion, 2) after 12-h iv GH infusion (1 IU/h), and 3) after 2-day sc GH treatment (8 IU/day), followed by 12-h iv infusion of GH (1 IU/h). The UNSR (millimoles per h) during alanine infusion was significantly lower when the subjects were receiving GH therapy [maximum +/- SE, 133.0 +/- 6.9 (saline) vs. 96.7 +/- 11.1 (12-h GH; P < 0.01) vs. 106.5 +/- 7.5 (2-day GH; P < 0.05)]. FHNC (liters per h) was similar in all three studies [30.3 +/- 1.2 (saline) vs. 26.6 +/- 3.4 (12-h GH) vs. 27.0 +/- 2.6 (2-day GH)]. Six GH-deficient adult patients were randomly studied twice: 1) on regular daily (at 2000 h) sc GH therapy (3 IU/m2.day), and 2) after discontinuation of GH for 2 days. The UNSR during alanine infusion was likewise significantly lower when the patients were receiving GH therapy [147.7 +/- 11.7 mmol/h (no GH) vs. 123.9 +/- 9.1 mmol/h; P < 0.01]. FHNC (liters per h) values were similar in the two studies [29.2 +/- 3.8 (GH) vs. 27.5 +/- 4.5 (no GH)]. Our data confirm the anabolic action of GH and show that short term GH deprivation is associated with catabolism in terms of increased UNSR. The finding of unaltered FHNC suggests a GH-induced extrahepatic regulation of amino nitrogen conversion, rather than a substrate-independent hepatic mechanism.

Control of non-insulin-dependent diabetes mellitus partially normalizes the increase in hepatic efficacy for urea synthesis

The relation of urea synthesis rate to blood alanine concentration was assessed in seven healthy controls and eight patients with non-insulin-dependent diabetes mellitus (NIDDM) before (hemoglobin A 1c [HbA 1c] = 9.9% ± 1.9%, mean ± SD) and after (HbA 1c = 7.9% ± 0.8%) improvement of metabolic control. Following an overnight fast, alanine was infused at a rate of 2 mmol/(h · kg body weight [BW]). The hourly rate of urea synthesis was determined as the urinary excretion of urea corrected for accumulation of urea in total body water (TBW) and intestinal hydrolysis. The functional hepatic nitrogen clearance (FHNC) was calculated as the slope of the linear relation of urea synthesis rate to blood alanine concentration. The glucagon level was increased by twofold at the first investigation, but was not increased at the second. The insulin level was moderately increased at both investigations. In controls FHNC was 21.8 ± 4.4 L/h, in poorly controlled patients it was increased to 36.6 ± 4.3 L/h ( P < .01), and following improvement of metabolic control it was not different from control levels at 28.6 ± 4.3 L/h. By correlation analyses, FHNC was found only to be related to the fasting glucose value, albeit weakly ( R 2 = .39). In conclusion, hepatic kinetics of urea synthesis in poorly controlled NIDDM patients are changed in favor of increased conversion of alanine N to urea N at any amino acid concentration. This perturbation is partially normalized by improved metabolic control.

Simplified approach to calculation of V, G, and nPCR for monitoring hemodialysis patients.

Urea kinetic modeling (KM) permits the calculation of urea volume (VKM), urea generation rate (GKM), and normalized protein catabolic rate (nPCRKM) but requires complex, iterative calculations. Simpler methods for estimation of these parameters (V(est), G(est), nPCR(est)) were compared with those obtained from kinetic modeling. Kinetic modeling was performed on 17 patients using the 3 BUN method, producing 19 data sets. All were within 25% ideal body weight and all had less than 20% difference between VKM and V(est). V(est) was estimated as 0.195 (height) + 0.296 (weight) - 14.01. G(est) was estimated, using interdialytic changes as: [formula: see text] where U is urinary urea excretion rate. nPCR(est) was estimated as: (G(est) x 9.35) + (0.294 x V(est)) x (0.58/V(est)). There was no significant difference (Student's t test) between mean +/- SD V(est) (41.24 +/- 3.86 L) and VKM (40.71 +/- 5.24 L), G(est) (7.23 +/- 1.92 mg/min) and GKM (7.04 +/- 2.10 mg/min), and nPCR(est) (1.12 +/- 0.24 g/kg/day) and nPCRKM (1.10 +/- 0.23 g/kg/day). Correlation between V(est) and VKM was poor (r2 = 0.56, slope = 0.41). Correlations between G(est) and GKM and nPCR(est) and nPCRKM were good (r2 = 0.95, slope = 0.87; and r2 = 0.99, slope = 1.02, respectively). Assessment of nutritional status using G(est) and nPCR(est) can be carried out with high degree of accuracy even if V(est) and VKM are not identical.

Effect of dietary protein restriction on the progression of renal failure: a prospective randomized trial

One hundred twenty-eight patients with different renal diseases and chronic renal failure, stratified according to the underlying disease, were enrolled in a randomized controlled trial to investigate the effects on the rate of decline of renal function of two diets, a controlled protein diet (CPD) of 1 g protein/kg ideal body-weight (i.b.w.)/day, and a low-protein diet (LPD) of 0.6 g protein/kg i.b.w./day, given for 27.1 +/- 21.8 months. Dietary compliance was assessed by a dietary questionnaire, dietary interviews and measurement of 24-h urinary urea excretion. At the end of 6 months, actual mean protein intake was higher than expected (1.06 +/- 0.25 g/kg i.b.w./day) in CPD patients, and (0.80 +/- 0.21 g/kg i.b.w./day) in LPD patients: values were similar at 12 and 18 months after the time of enrollment. The end-point, defined as halving of creatinine clearance, was reached in 40% of patients on CPD, and in 28.6% of those on LPD (P = 0.038 by comparative life-table analysis). Multivariate regression analysis confirmed that CPD was associated with a higher risk of progression than LPD, and that two additional parameters (creatinine clearance at the time of randomization and average proteinuria during the follow-up) were significant independent risk factors, even more important than protein intake.

Effects of intraruminal infusions of urea, sucrose or urea plus sucrose on plasma urea and glucose kinetics in sheep fed chopped lucerne hay

SUMMARYThe effect of rumen fermentation on the relationship between urea and glucose kinetics was examined in sheep fed chopped lucerne hay with intraruminal infusions of water, urea, sucrose, or urea plus sucrose at Palmerston North, New Zealand in 1986. Sheep were fed hourly and infused intraruminally with water (1200 m1/day), or a similar volume containing either urea alone (13·7g/day), sucrose alone (178·2 g/day) or urea (14·6 g/day) plus sucrose (175·0 g/day). The added sucrose resulted in a lower rumen ammonia concentration (P&lt; 0·05), lower plasma urea concentration (P&lt; 0·05) and reduced urinary urea excretion (P&lt; 0·05). Urea recycled to the gut tended to increase with the sucrose, urea or sucrose plus urea treatments compared with the water treatment. The fermentation of sucrose in the rumen resulted in decreases in ruminal pH (P&lt; 0·05) and in the ratio of acetate to propionate (A:P) (P&lt; 0·05). The infusion of sucrose also increased the concentration of propionate in rumen fluid (P&lt; 0·05), tended to increase the plasma glucose level and increased plasma glucose irreversible loss (P&lt; 0·05). The infusion of urea resulted in an increase in the plasma urea level (P&lt; 0·05), urea pool size (P&lt; 0·05) and urea irreversible loss (P&lt; 0·01). However, urea infusion did not affect glucose metabolism or volatile fatty acid (VFA) fermentation. The effects of sucrose infusion on glucose and urea kinetics were broadly similar when given alone or with urea, apart from changes in the urea degradation rate. It was concluded that the additional fermentative activity resulting from sucrose increased propionate production which, in turn, was available for glucose production, thus ‘sparing’ amino acids for tissue protein utilization and reducing urea excretion.

Renal responses to magnesium lithospermate B in rats with adenine‐induced renal failure

AbstractA study was conducted to investigate the effects of magnesium lithospermate B on the uraemic symptoms and development of hypertension in rats with adenine‐induced renal failure. Chronic administration of 10 mg/kg body weight/day magnesium lithospermate B significantly reduced serum urea nitrogen, creatinine, methylguanidine, guanidinosuccinic acid and inorganic phosphate, accompanied by increased urinary excretion of urea, creatinine and electrolytes. In addition, renal tissue blood flow was significantly increased and mean blood pressure significantly decreased in the magnesium lithospermate B‐treated group compared with the control group. These results confirm that chronic administration of magnesium lithospermate B to rats with adenine‐induced renal failure ameliorates the uraemic symptoms and development of hypertension by improving renal haemodynamics and electrolyte metabolism.

Effect of chemotherapy on the energy and protein metabolism of children near the end of treatment for acute lymphoblastic leukemia

Eight children in the final 3 mo of chemotherapy for acute lymphoblastic leukemia were studied while on oral 6-mercaptopurine (6MP) maintenance therapy and then again 4-9 mo after chemotherapy had been completed. Six of the eight were also studied a second time while on 6MP in the 24-h period after receiving intravenous methotrexate (MTX). 6MP reduced protein oxidation after a test meal and reduced fasting urinary urea excretion by enhancing the reutilization of endogenous amino acids for protein synthesis. MTX had no detectable effects on protein metabolism but reduced overnight carbohydrate utilization by enhancing fat utilization. A similar enhancement of fat utilization was evident after a test meal. The two drugs in combination resulted in effects on protein and energy metabolism that were the sum of the individual effects plus an increase in the rate of whole-body protein turnover and synthesis.

Arginine affects urea synthesis in rats treated with thyroid hormone.

The purpose of the present study was to determine whether the regulation of urea synthesis was mediated through the activation of N-acetylglutamate synthesis by arginine and whether the concentration of glutamate or activity of N-acetylglutamate synthetase might control N-acetylglutamate concentration when the thyroid status was manipulated. Three groups of rats were given 6-propyl-2-thiouracil (PTU, thyroid inhibitor) without triiodothyronine (T3) treatment, treated with PTU + T3 or treated with neither PTU nor T3 (control). Urinary excretion of urea, liver concentration of N-acetylglutamate and plasma concentration of arginine in rats given PTU + T3 were significantly lower than in rats given PTU alone. Liver concentration of N-acetyl-glutamate was correlated with plasma concentration of arginine (r = 0.842, P < 0.001). The activity of N-acetylglutamate synthetase and glutamate concentration in liver of the PTU + T3-treated group were significantly higher than in the group treated with PTU alone. Arginine administration (0.5 mmol/100 g body wt) elevated the liver concentration of N-acetylglutamate in all three groups. The results suggest that the greater concentration of arginine in the hypothyroid (PTU alone) rats is likely to increase the N-acetylglutamate concentration and stimulate urea synthesis.

Role of Amino Acid-catabolizing Enzymes in Urea Synthesis for Rats Treated with the Thyroid Hormone

The purpose of the present study was to determine whether the regulation of urea synthesis was mediated through the supply of nitrogen by amino acid-catabolizing enzymes and whether the concentration of acetylCoA would control the N-acetylglutamate concentration when the thyroid status was manipulated. Experiments were conducted on three groups of rats, each being given 6-propyl-2-thiouracil (PTU, thyroid inhibitor) without a triiodothyronine (T3) treatment, or PTU + T3, or neither PTU nor T3 (control), respectively. The urinary excretion of urea, the liver concentration of N-acetylglutamate, and the hepatic activities of serine dehydratase, threonine dehydratase, alanine transaminase (GPT) and aspartate transaminase (GOT) in rats given PTU + T3 were significantly lower than those in rats given PTU alone. The activity of glutamate dehydrogenase and the concentrations of free amino acids and acetylCoA in the liver of the PTU + T3-treated group were significantly higher than those in the group treated with ...

Measurement of urea kinetics with a single dose of [15N15N]-urea in free-living female vegetarians on their habitual diet

Urea kinetics were measured in a group of six healthy female vegetarians with no restrictions on lifestyle. Following a single oral dose of [15N15N]-urea, all urine was collected for 48h and the amounts of [15N15N]-urea and [15N14N]-urea were measured and used to determine the rates of urea production and urea salvage by the colonic microflora. Dietary intake was recorded over the same period and the intake of energy and nitrogen was derived from food composition tables. There was wide inter-individual variability within the group. Body mass index (BMI) ranged from 18.8 to 25.6 kg/m2, energy intake between 7.1 and 10.7MJ/day and protein intake between 46.4 and 73.6g/day. When expressed in relation to body mass, nitrogen intake ranged between 106 and 209mgN/kg/day, urea production between 114 and 248 mgN/kg/day and urinary urea excretion between 78 and 174 mgN/kg/day. The proportion of the urea produced which was excreted in the urine varied with the protein intake from 50 to 70%, with 30 to 50% of the ure...

Changes in Serum Amino Acid Concentrations during Prolonged Endurance Running.

Eight endurance trained distance runners (5 male and 3 female) ran on a treadmill at 60% of their VO2max for 3 h. Blood samples (about 12 ml) were taken immediately prior to the exercise, and thereafter every 30 min during and at the end of exercise. Urinary urea excretion was determined for the day of exercise, and for a control day a week after the exercise. Blood samples were analyzed for glucose, free fatty acids, urea and free amino acids concentrations. As the exercise was continued, there was a gradual decrease in the concentrations in serum of alanine and proline such that the concentrations of both the amino acids were significantly less at the end of exercise than the resting values (p < 0.01). These changes appeared to be highly correlated (r = 0.981, p < 0.05). The serum glucose concentration increased significantly (p < 0.05) after 30 min of exercise, remained significantly elevated until 150 min of exercise and then decreased to reach the resting value at the completion of the exercise. Serum free fatty acid (FFA) concentration was significantly higher at the end of exercise compared to the resting value. The increase in serum FFA concentration and the decreases in the concentrations in serum of alanine and proline were also found to be highly correlated (alanine versus FFA: r = -0.986, p < 0.05; proline versus FFA: r = -0.961, p < 0.05). The total urinary urea excretion (332 +/- 43 mmol versus 424 +/- 46 mmol) and urine volume (978 +/- 187 ml versus 1,480 +/- 245 ml) were less on the day fo exercise than on the control day. The decrease in urine volume was found to be significant (p < 0.05).

Compliance and effects of nutritional treatment on progression and metabolic disorders of chronic renal failure

Low-protein, low-phosphorus diets (LPD) are prescribed to patients with chronic renal failure (CRF) to slow down the rate of progression of CRF and to control uraemic symptoms. A satisfactory adherence of patients to the prescribed diet is needed to meet these two goals. We studied the compliance of CRF patients to a LPD providing daily (per kg body weight) 0.3 g protein, 3-5 mg phosphorus, 35 kcal, and supplemented with essential amino-acids and keto-analogues. Forty CRF patients were studied for 23.3 +/- 10.8 months (range 12-45). Compliance to LPD was evaluated by dietary inquiry and protein intake estimated from urinary urea excretion. According to compliance to LPD, patients were retrospectively assigned to the compliant (n = 27) or the non-compliant (n = 13) group. GFR measured by the urinary clearance of [51Cr]-EDTA was identical in the two groups at the start of the study: compliant patients 15.7 +/- 5.3 ml/mn, non-compliant patients 15.4 +/- 5.9 ml/mn. The decrease of GFR was -0.08 +/- 0.22 ml/min per month in compliant patients versus -0.31 +/- 0.37 ml/min per month in non-compliant patients (P < 0.02). These results were not demonstrated if the progression of CRF was assessed by the linear regressions over time of creatinine clearance or the reciprocal of creatinine. Serum bicarbonate, serum phosphorus and PTH levels were corrected by LPD in compliant patients (P < 0.005 for all parameters) but not in non-compliant patients. These results suggest that evaluation of compliance is necessary to assess the response of CRF patients to LPD, whether the aim is to slow the progression of CRF or to control its metabolic consequences. A beneficial effect of compliance to LPD was demonstrated upon these two goals.

Effect of high-protein diet on renal concentration capacity in rabbits

In the present studies, we have found that New Zealand White rabbits kept on normal rabbit chow (16% protein, LP) are unable to raise fractional free water reabsorption [TCH2O divided by glomerular filtration rate (GFR)] as the fractional osmotic load (Cosm/GFR) is increased. Acute administration of urea (400 mosmol/l) or indomethacin (10 mg/kg iv bolus, followed by 0.25 mg/min infusion) corrects the defect. Moreover, rabbits kept for 2 wk on a 40% protein diet (HP) showed marked improvement in their renal concentration capacity. Balance studies showed that, in rabbits on HP, urine prostaglandin E2 (PGE2) excretion was lower while GFR, urine urea, and osmolar excretion were significantly higher than in rabbits in the LP group. Medullary tissue electrolytes in the HP vs. LP group were as follows: urea, 1,035 +/- 90 vs. 790 +/- 60 mmol.l-1 x g wet tissue wt-1; tissue Na+, 548 +/- 96 vs. 298 +/- 37 meq.l-1 x g wet wt-1; and K+, 201 +/- 43 vs. 99 +/- 16 meq.l-1 x g wet wt-1. Also, medullary slices from animals on HP had a lower PGE2 synthesis than those on LP when stimulated with angiotensin II (ANG II). Papillary plasma flow (PPF) measured by the accumulation of 125I-labeled albumin, after infusion of vasopressin, was 13.7 +/- 2.0 in the HP group and 22.7 +/- 3.4 ml.min-1 x 100 g-1 in the LP group. These findings suggest that lower PPF and higher urea and electrolyte content in the medullary interstitium of HP intake results from inability to produce medullary PGE2 even during ANG II or antidiuretic hormone (ADH) stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of dietary protein and phosphate restriction to retard the rate of progression of chronic renal failure: a prospective, randomized, controlled trial

Ninety-five patients (63 male, 32 female), age 45 +/- 2 years (mean +/- SEM) with chronic renal failure of varied aetiology were randomized to receive either a conventional low protein diet (0.6 g/kg/day protein, 800 mg phosphate; n = 33), a low phosphate diet (providing approximately 1000 mg phosphate plus an orally administered phosphate binder, minimum protein intake 0.8 g/kg/day; n = 30) or to control (minimum protein intake 0.8 g/kg/day, no phosphate restriction; n = 32). Patients were reviewed for a minimum of 6 months before randomization and were withdrawn from the study if plasma creatinine exceeded 900 mumol/l, plasma phosphate was greater than 2.0 mmol/l or at the onset of uraemic symptoms. Following randomization patients were studied for an average of 19 +/- 3 months. Mean plasma creatinine rose from 398 +/- 33 to 600 +/- 50 mumol/l. Dietary protein intake was estimated at 0.69 +/- 0.02 g/kg/day in the low protein group, 1.02 +/- 0.05 in the low phosphate and 1.14 +/- 0.05 in the controls, phosphate intake was 815 +/- 43, 1000 +/- 47, and 1315 +/- 57 mg/day, respectively. Urinary urea excretion and protein catabolic rates were significantly reduced (p less than 0.01) only in those on protein restriction, at 213 +/- 9 mmol/24 hours and 0.71 g/kg/day, respectively. Phosphate excretion was significantly lower (p less than 0.05) in both the low protein group (17.9 +/- 0.8 mmol/24 hours) and the low phosphate group (18.6 +/- 1.0 mmol/24 hours) compared to controls. Changes in body weight, muscle mass and serum transferrin, albumin and immunoglobulins were comparable between the groups. Mean blood pressure following randomization was 150/89 +/- 3/1 (low protein), 148/87 +/- 3/1 (low phosphate) and 146/87 +/- 3/1 (controls). Progression of renal failure was analysed by rate of all of creatinine clearance (ml/min/1.73 m2/month), by rate of deterioration derived from reciprocal plasma creatinine against time plots (1/mmol/year) and to assess individual patient's response to treatment by two phase linear regression ('breakpoint') analysis of reciprocal plasma creatinine/time plots. Progression was analysed only in patients seen for at least 3 months following randomization. The rate of fall of creatinine clearance was not significantly different between the groups (ANOVA): 0.56 +/- 0.08 ml/min/1.73 m2/month (low protein, n = 28), 0.44 +/- 0.07 (low phosphate, n = 23) and 0.69 +/- 0.11 (control, n = 27).(ABSTRACT TRUNCATED AT 400 WORDS)

Dietary Supplementation With l-Arginine Ameliorates the Progression of Renal Disease in Rats With Subtotal Nephrectomy

We studied the effect of dietary supplementation with L-arginine for 6 weeks on the progression of renal disease in female Sprague-Dawley rats subjected to sham-operation (groups 1 and 2) or surgical ablation of 85% to 90% of the total renal mass (groups 3 and 4). All rats were fed a standard rat chow containing 22.8% protein. Rats in groups 1 (n = 5) and 3 (n = 9) served as controls and drank tap water ad libitum. Rats in groups 2 (n = 6) and 4 (n = 6) drank tap water supplemented with 1% L-arginine. Rats in groups 1 and 2 had similar values for glomerular and tubular function and serum chemistries 6 weeks after sham-operation. Sham-operated rats given L-arginine had significantly greater urine urea excretion than similar rats drinking tap water. Rats with subtotal nephrectomy (groups 3 and 4) had a significantly higher blood pressure, greater proteinuria, and a significantly lower plasma albumin than sham-operated rats (groups 1 and 2). Rats with remnant kidneys given 1% L-arginine (group 4) had significantly greater values for glomerular filtration rate (GFR) and P-amino hippurate (PAH) clearance than similar rats given tap water (group 3), despite comparable levels of systemic blood pressure, hematocrit, body weight, plasma chemistries, including L-arginine, and urine chemistries, except urea excretion. The remnant kidney of rats given L-arginine (group 4) had a greater number of normal or minimally abnormal glomeruli and fewer interstitial changes than that of rats given tap water (group 3).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of dietary pectin on rapid catch-up weight gain and urea kinetics in children recovering from severe undernutrition.

The rates of weight gain and urea kinetics were measured in 12 children receiving one of two energy dense, isonitrogenous formulae (711 kJ/kg/day, 170 kcal/kg/day) during recovery from severe undernutrition. Both formulations contained added arachis oil but in one a source of complex carbohydrate was added in the form of pectin (3.4% of total energy). The children taking the pectin diet had a rate of weight gain which was highly significantly less (7 g/kg/day) than the children not receiving pectin (14 g/kg/day). Urea production was significantly less on the pectin diet (0.37 +/- 0.07 vs 0.55 +/- 0.18 gN/kg/day). On the pectin diet there was a reduction in the rate of excretion of urea in urine and in the rate at which urea nitrogen was salvaged by the lower bowel, but these differences failed to reach statistical significance.

Changes in Liver Concentration of N-Acetylglutamate and Ornithine are Involved in Regulating Urea Synthesis in Rats Treated with Thyroid Hormone

The purpose of this study was to elucidate the mechanism by which thyroid hormone alters urea synthesis. A set of three experiments was investigated in three groups of rats given 6-propyl-2-thiouracil (a thyroid inhibitor) without triiodothyronine treatment, treated with 6-propyl-2-thiouracil plus triiodothyronine or neither 6-propyl-2-thiouracil nor triiodothyronine (control). We attempted to determine whether the concentration of ornithine and N-acetylglutamate regulated urea synthesis and whether activities of two ornithine-catabolizing enzymes accounted for changes in ornithine concentration. Urinary excretion of urea and the liver concentration of N-acetylglutamate and ornithine in rats given 6-propyl-2-thiouracil plus triiodothyronine were significantly lower than in rats given 6-propyl-2-thiouracil alone. The liver concentration of N-acetylglutamate was correlated to urea excretion (r = 0.911, P < 0.001). The activities of carbamylphosphate synthetase, ornithine aminotransferase and ornithine decarboxylase in liver of the group treated with 6-propyl-2-thiouracil alone were significantly lower than those of the 6-propyl-2-thiouracil plus triiodothyronine-treated group. The results suggest that a higher liver concentration of N-acetylglutamate and ornithine in the hypothyroid (6-propyl-2-thiouracil only) rats is likely to stimulate urea synthesis. The thyroid hormone-induced increase in activities of ornithine catabolizing enzymes may be primarily responsible for changes in ornithine concentration.

The effect of dietary protein intake on glutamine and glutamate nitrogen metabolism in humans

The response of glutamine and glutamate kinetics were studied in five healthy young adult men on diets containing deficient (0.1), adequate (0.8), or surfeit (2.2 g.kg-1.d-1) amounts of protein. Glutamate, glutamine, and phenylalanine kinetics were measured in the postabsorptive state at the end of each diet period. Urinary urea and ammonia excretion correlated with protein intake (the sum of the two was 2.1 +/- 0.2, 5.7 +/- 0.3, and 11.9 +/- 1.2 g N g.kg-1.d-1 for the respective 0.1, 0.8, and 2.2 g.kg-1.d-1 protein intakes). Glutamate and glutamine concentrations varied inversely with protein intake. Phenylalanine concentrations and phenylalanine flux did not change significantly with the changing protein intake. Both glutamate and glutamine fluxes varied inversely with protein intake (glutamate flux was 177 +/- 15, 120 +/- 10, and 125 +/- 11 mumol.kg-1.h-1 and glutamine flux was 373 +/- 29, 343 +/- 26, and 318 +/- 15 mumol.kg-1.h-1 at the respective 0.1, 0.8, and 2.2 g.kg-1.d-1 protein intakes). These changes in glutamine or glutamate flux in response to alterations in dietary protein intake were attributable to changes in de novo production.

Renal Hemodynamics and Urinary Concentrating Capacity in Protein Deprivation: Role of Antidiuretic Hormone

The role of antidiuretic hormone (ADH) in the renal concentration defect and hemodynamic changes in protein malnutrition was evaluated in rats with diabetes insipidus (DI) after 2 weeks of low protein feeding. Free water reabsorptive capacity (TcH2O), glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured in the protein deprived rats and in DI rats fed a normal protein diet. The effect of urea supplementation of the low protein diet on renal concentrating capacity was also evaluated. In addition, the renal hemodynamic response to acute administration of ADH was measured and correlated with changes in plasma renin concentration and renal renin content (RRC). Protein deprivation in DI rats resulted in reduced urine osmolality and urea excretion, differences which were reversed by urea supplementation. Protein deprivation did not affect free water reabsorptive capacity but did reduce GFR and RPF. Acute ADH administration significantly increased GFR and RPF in protein-deprived rats; these changes were associated with a reduction in RRC and release. These results suggest that dietary protein restriction does not directly affect the tubular capacity to generate and reabsorb free water. The hemodynamic changes seen in protein deprivation are not mediated by ADH and may be secondary to increased intrarenal angiotensin II.

Effect of Selenium Deficiency on Urinary Ketone Body Excretion in Starved Rats

Abstract Rats were fed a Se-deficient (Se content: 0.011 μ g/g) or a Se-adequate diet (the basal diet supplemented with 0.1 μg Se/g as sodium selenite). On the 22nd week of the feeding period, the rats were starved for 72 h and the urinary excretion of ketone bodies (acetoacetate and 3-hydroxybutyrate), urea, and creatinine were examined. The urinary excretion of ketone bodies were markedly higher in the Se-deficient rats than in the Se-adequate rats 24 h after the start of starvation, while the excretion of urea and creatinine were similar in the Se-deficient and Se-adequate rats. Se status did not effect on the plasma urea and creatinine contents as well as urinary N-acetyl-β-D-glucosaminidase activity; renal function was not impaired by Se deficiency. These results indicate that Se deficiency causes an increase of urinary ketone body excretion in starved rats and that the increase is ketone-specific with no changes in major urinary profiles.