Urinary Urea Excretion Research Articles

Uréia para Vacas em Lactação: 2. Estimativas do Volume Urinário, da Produção Microbiana e da Excreção de Uréia

Esta pesquisa foi desenvolvida, utilizando 15 vacas lactantes (Holandês x Gir) alimentadas à vontade com rações isoprotéicas constituídas de 60% de silagem e 40% de concentrado na matéria seca (MS) e 0; 0,7; 1,4; e 2,1% de uréia, correspondentes aos teores de 2,08; 4,01; 5,76; e 8,07% de proteína bruta na forma de compostos nitrogenados não-protéicos (NNP), com os objetivos de desenvolver metodologia não-invasiva, para estimar a produção de proteína microbiana, utilizando-se a excreção total de derivados de purinas (DP); avaliar as concentrações de creatinina, uréia e N-uréia no plasma e no leite; e comparar as excreções de DP e uréia obtidas a partir de coletas de urina total e spot. Os animais tinham peso vivo médio inicial de 511,8 kg e foram distribuídos ao acaso entre tratamentos. O período experimental teve duração de 90 dias para cada vaca, iniciando-se imediatamente após o parto. Os resultados obtidos foram avaliados estatisticamente por análises de variância e de regressão. As amostras de urina foram obtidas a partir de coletas com 24 horas de duração ou a partir de amostra de urina obtida aproximadamente 4 horas após a alimentação (urina spot), enquanto as de sangue foram obtidas 4 horas após o fornecimento do alimento. As concentrações de uréia e N-uréia no plasma e leite, assim como a excreção de creatinina, que apresentou valor médio de 23,60 mg/kg PV, não foram afetadas pela adição de quantidades crescentes de NNP à ração. As excreções urinárias de uréia, alantoína, ácido úrico e DP, as purinas absorvidas e a produção de N microbiano não foram influenciadas pela dieta. As excreções diárias estimadas de uréia, alantoína e ácido úrico seguiram o mesmo padrão obtido pela coleta de 24 horas de duração. Amostra spot de urina foi capaz de estimar satisfatoriamente a excreção de DP e, subseqüentemente, a produção de N microbiano.

Effect of N fertilisation rate, energy supplementation and supplementation strategy on efficiency of N utilisation in the sheep rumen

The effect of nitrogen (N) fertilisation (200 vs. 400 kg N ha‐1 year‐1) of pasture cut in the beginning (end of May) and the end (end of August) of the grazing season and of simultaneous or separated feeding of maize and grass (400 kg N ha‐1 year‐1) on efficiency of N utilisation in the rumen has been studied using four rumen canulated wethers. Doubling N fertiliser rate increased grass CP production by about 60%, but induced extensive excess of rumen degradable N, reflected in high urinary urea excretion (rpearson = 0.747). The latter was lower (74% at the maximum) when feeding less fertilised or older grass or when supplementing with maize silage. Although simultaneous feeding of maize silage with grass changed patterns of rumen ammonia concentrations, no change in urinary excretion of purine derivatives was observed. Hence, faecal or urinary N excretion was unaffected by the supplementation strategy. Microbial growth efficiency was estimated from urinary excretion of purine derivatives and fermented OM. The latter was calculated from total rumen CH4 production, based on rumen fermentation stoichiometry and taking into account proportional concentrations of individual volatile fatty acids. Higher levels of intake tended to improve rumen microbial growth efficiency slightly (rpearson=0.406), which, however, could not compensate for the reduced effective rumen DM degradability (rpearson =‐0.442). The latter was apparently associated with a partial shift of the fermentation from the rumen to the hindgut, as suggested from the negative correlation (rprarson =‐0.745) between faecal RNA concentrations and rumen effective degradability.

Nitrite/Nitrate responses to endotoxin in calves.

Plasma concentrations and urinary excretions of nitrite plus nitrate (NOx) increase in heifers after endotoxin-induced nitric oxide synthase activation. The rise can be enhanced by administration of arginine, the substrate for the production of nitric oxide, whose effects may be modified by the iron status. In 10-week-old veal calves (six Simmental x Red Holstein) arginine (0.5 g/kg body weight for 6 h) was intravenously infused. At 2 h after the start of the infusions Escherichia coli endotoxin O26:B6 (2 microg/kg body weight) was intravenously injected. This caused a rise of rectal temperature, heart rate, respiration rate, and of urinary NOx excretion, but not of plasma NOx concentrations, in contrast to the experience with older cattle to which the same amounts of arginine were infused before and during endotoxin administration. In 8-week-old veal calves (18 Simmental x Red Holstein) the question of whether oral supplementation with arginine and iron modifies NOx responses to endotoxin (2 microg/kg) was also investigated. The calves were divided between three groups (GrA-, GirA+, GrC) and before endotoxin injections GrA- was fed 0.5 g arginine/kg for 4 days, GrA+ was fed 0.5 g arginine/kg for 4 days plus 80 mg iron/kg milk for 2 weeks, whereas GrC was not supplemented with arginine or iron. Iron supplementation increased plasma iron concentrations and arginine supplementation increased plasma arginine and urea concentrations and urinary urea excretion. Ensuing administration of endotoxin enhanced plasma tumour necrosis factor-alpha concentrations, rectal temperature, heart rate, and respiration rate, but not plasma NOx concentrations in GrC and GrA- and only transiently and slightly increased plasma NOx concentrations in GrA+ but did not affect urinary NOx excretions. In conclusion, the expected stimulation of NOx responses to endotoxin by intravenous arginine infusion appears to be much weaker in young veal calves than in older cattle. The NOx responses in young veal calves were not modified if arginine was orally administered and plasma NOx were barely enhanced by combined oral supplementation of arginine and iron.

Produção de proteína microbiana e estimativas das excreções de derivados de purinas e de uréia em vacas lactantes alimentadas com rações isoprotéicas contendo diferentes níveis de compostos nitrogenados não-protéicos

Foram objetivos do presente trabalho estimar a produção de proteína microbiana, utilizando-se a excreção total de derivados de purina (DP); comparar as excreções de DP e uréia obtidas a partir de coletas spot de urina com aquelas observadas em coletas de 24 horas; e avaliar as concentrações de N-uréia no plasma e no leite e as excreções de uréia. Utilizaram-se 16 vacas holandesas em quatro quadrados latinos balanceados 4 x 4, distribuídos de acordo com o período de lactação. Cada período experimental teve duração de 21 dias, sendo sete dias de adaptação e 14 dias para as coletas de amostras. As quatro rações experimentais, isoprotéicas, foram formuladas para conter na base da MS 60% de silagem de milho e 40% de concentrado. Foram utilizados níveis crescentes de uréia no concentrado: 0; 0,7; 1,4; e 2,1%, correspondentes aos níveis de proteína bruta na forma de compostos nitrogenados não-protéicos (NNP) das rações de 2,22; 4,18; 5,96; e 8,09%, respectivamente. O volume urinário foi estimado utilizando amostras de urina obtidas quatro horas após a alimentação (spot), dividindo-se a excreção diária média de creatinina pela concentração de creatinina na urina spot. O volume urinário e as excreções de DP e de uréia, estimados por meio da urina spot, não diferiram daqueles obtidos pela coleta de urina por 24 horas. As produções de N-microbiano estimadas e obtidas apresentaram valores máximos de 198,05 e 196,96 g/dia, nos níveis de compostos nitrogenados não-protéicos de 5,33 e 4,44%, respectivamente. A concentração de alantoína no leite decresceu linearmente com o aumento dos níveis de NNP na dieta e representou 4,5% da excreção total de DP. A excreção de creatinina não foi afetada pelos níveis de NNP na dieta (23,41 mg/kg PV), enquanto as excreções estimada e obtida de uréia, as concentrações de uréia e N-uréia no plasma e no leite aumentaram linearmente com os níveis de NNP na ração. Concentrações plasmáticas e no leite de N-uréia de 19 a 20 mg% e 24 a 25 mg%, respectivamente, representariam valores limites a partir dos quais ocorreriam perdas de compostos nitrogenados.

Guar gum does not impair the absorption and utilization of dietary nitrogen but affects early endogenous urea kinetics in humans

Viscous gums enhance viscosity in the upper gastrointestinal lumen, quickly disturbing motility and promoting fluid secretion. We sought to determine whether guar gum could acutely affect the absorption and utilization of dietary nitrogen and whether these luminal effects could also perturb the kinetics of urea. We studied the short-term effect of adding 1% of highly viscous guar gum to a (15)N-labeled protein meal (30 g soy protein isolate in 500 mL water) during the postprandial phase in humans. The effects on bioavailability were studied by using the [(13)C]glycine breath test (to assess gastric emptying) and (15)N enrichment in plasma amino acids (for systemic amino acid bioavailability). The kinetics of dietary and endogenous urea were assessed in plasma and urine. Guar gum modulated the gastric emptying kinetics of the liquid phase of the meal slightly (P < 0.05), but had no significant effect on either the systemic appearance of dietary amino acids or plasma and urinary dietary urea kinetics. Without significantly affecting plasma urea concentrations, guar gum reduced by approximately 40% the urinary excretion of endogenous urea for the first 2-h period after the meal (P < 0.01), although endogenous urinary excretion was similar at later stages. Guar gum did not significantly affect the bioavailability or utilization of dietary protein. We showed an early effect of guar gum on endogenous urea kinetics, which most probably arose from very early, short-term stimulation of the intestinal disposal of endogenous urea, at the expense of its urinary excretion.

Level of hydration and renal function in healthy humans

High hydration is commonly used in renal studies to improve the completeness of urine collection. The renal effects of hydration are not well defined. Renal function was studied under fasting conditions (baseline) and after a meat meal (2 g of protein/kg body weight) in 12 healthy adults on a low and high hydration regimen of 0.5 and 4 mL of oral water per kg body weight/30 min, respectively. Urine flow, urinary and plasma Na, K, urea, and osmolality were stably different on low and high hydration regimens. At baseline, there were significant or borderline significant correlations of plasma and urine osmolality with glomerular filtration rate (GFR; inulin clearance) only in the low hydration regimen. GFR was higher in the low than the high hydration regimen at all time points. The difference was significant at baseline (19.2%) and at 90 to 180 minutes after the meal (14.4%). After the meal, GFR increased significantly over baseline values only in the high hydration regimen (30.0% at peak time). Urinary excretion of Na, urea, and osmoles was lower in the low than the high hydration regimen at all time points: The difference was significant for Na (at baseline) and osmoles (all time points). Urinary K excretion was not different in the two regimens. After the meal, there were significant increases in urinary excretion of Na (in the low hydration regimen) and urea (90 to 180 min after the meal). In fasting adults, high hydration lowered GFR and increased natriuresis. After a meat meal, GFR increased only in the high hydration regimen and natriuresis only in the low hydration regimen. Hydration affects GFR and natriuresis under fasting conditions and after a meat meal.

Growth hormone/insulin-like growth factors axis in children undergoing cardiac surgery.

To describe the sequential changes in the growth hormone (GH)/insulin-like growth factors axis and their relationship with nitrogen balance in children following cardiac surgery. Prospective, descriptive study. Pediatric intensive care unit of a university hospital. Twenty three postoperative cardiac surgical patients after bypass. Blood and urine samples were taken on days 1, 2, and 7 of pediatric intensive care unit admission. An intraanesthesia, presurgery sample was also obtained. Serum concentrations of insulin, insulin growth factor-I (IGF-I), insulin growth factor binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), growth hormone binding protein (GHBP), and urinary concentrations of GH and free cortisol (UFC) were measured on days 1, 2, and 7 of the study period. C-reactive protein and prealbumin, were also measured in blood samples as conventional markers of inflammatory or nutritional status. Pediatric Risk of Mortality II score and UFC were used as indicators of acute stress. The nitrogen balance and urinary nitrogen urea excretion were used as markers of catabolic state. Urinary concentrations of GH were high from days 1 to 7. Plasma concentrations of IGF-I and GHBP were low and remained low throughout the study period. IGFBP-3 levels were below normal but without reaching statistical significance. The IGFBP-1 levels were initially high but descended progressively toward normal values. Urinary nitrogen urea production was persistently elevated and was associated with a negative nitrogen balance. No relationship was found between nitrogen balance and IGF-I, prealbumin, or C-reactive protein. A GH-resistant state is observed in postoperative children following cardiac surgery. Stress response is characterized by an elevation of growth hormone secretion that is not followed by the corresponding increment in IGF-I and IGFBP-3 concentrations. These hormonal changes may be permissive for the catabolic state of these patients. IGF-I and IGFBP-1 and -3 are not related to either nitrogen balance or urinary nitrogen urea excretion.

High versus low protein diets to mink‐postprandial plasma urea and creatinine response, osmotic load and pattern of nitrogen and electrolyte excretion

Nitrogen balance, pattern of excretion of nitrogenous end‐products, endogenous urinary N excretion, postprandial plasma urea and creatinine, osmotic load, urinary electrolyte excretion and water intake/output relationships were studied in 12 adult female mink fed a high protein diet (HP; n=6) providing about 155g protein/kg or a low protein diet (LP; n=6) providing about 95 g protein/kg. Two balance periods of each 3 d were used and diets were fed raw or cooked. After the last balance period followed a 48 h fasting period. Postprandial plasma urea and creatinine were studied for 48 h following a test meal given after an overnight fast. Osmotic load was determined based on collection of non‐acidified urine carried out during 48h. Level of protein supply did not affect N balance, being close to zero, whereas slightly negative balances were achieved for fasting animals. Protein supply was clearly reflected in excretion of urinary urea and allantoin but not in creatinine and uric acid. Endogenous urinary N excretion was estimated by a second order regression equation giving an intercept of 280mg/kg0.75. Post‐prandial plasma urea concentrations were strongly influenced by protein supply, HP animals having substantially higher peaks than LP animals, but values returned to fasting values within 24 h after the test meal. Plasma creatinine followed a biphasic pattern with a peak about 2 h after feeding and a nadir approximately 6 h after feeding. Physical form of diet influenced postprandial urea, animals fed raw diets having a higher peak, but not creatinine. The HP diet provided almost the double osmotic load of the LP diet and a corresponding increase in urine volume. The resulting water balances were identical irrespective of diet, showing that water intake/output relationships are very accurately regulated.

Dietary lactulose decreases apparent nitrogen absorption and increases apparent calcium and magnesium absorption in healthy dogs

To study the effect of lactulose on the route of nitrogen excretion, we fed six healthy, adult dogs on diets containing either 0, 1 or 3 g lactulose/MJ metabolizable energy according to a 3 x 3 Latin square design. The results were analysed to identify statistically significant linear trend effects of lactulose. Faecal pH was significantly lowered by lactulose. Faecal ammonium and nitrogen excretion tended to be raised by lactulose feeding whereas urinary urea excretion was significantly reduced. Lactulose feeding significantly lowered apparent nitrogen digestibility. It is concluded that lactulose feeding shifts nitrogen excretion from urine to faeces in dogs which may be beneficial for liver patients. The data are in line with the concept that lactulose stimulates bacterial growth in the colon which in turn enhances faecal nitrogen excretion and lowers the entry of colonic ammonia into the bloodstream, leading to a lesser workload for the liver and less urinary nitrogen excretion. Lactulose consumption was also found to produce a dose-dependent increase in the apparent absorption of calcium and magnesium, but not phosphorus.

Short-term effects of a hypocaloric diet on nitrogen excretion in morbid obese women.

To determine whether the daily pattern of urine excretion of N wastes is affected by obesity and very low-calorie diets (VLCD). The plasma amino acid, urea and other energy parameters, as well as the urinary excretion of total nitrogen, urea and creatinine were studied in obese and normal-weight women. The obese women's data were obtained under hospital basal controlled conditions (8.1 MJ/day) and after 3 days of VLCD diet (1.9 MJ/day) controls were studied only once (5.8 MJ/day). The hourly excretion patterns of total N, urea and creatinine were determined from the composition of each bladder voiding. Twenty morbidly obese and 10 age-matched normal-weight control women. Plasma amino acid levels were higher in obese women, which showed a limited ability to metabolize amino acid hydrocarbon skeletons. Neither differences in the patterns between groups nor total 24 h values for urine volume were found. Total N and urea excretion diminished under VLCD diet. Hourly creatinine excretion showed a flat pattern and was higher in obese women than in the controls, VLCD diet diminished the amount of creatinine excreted in 24 h. The early change in energy availability that the creatinine excretion figures reflect may result from the energy conservation mechanisms induced in response to energy restriction. The early onset of this effect (3 days, and the extent of decrease (approximately 19%) also suggest that the impact of VLCD on the muscle energy budget of the obese is more marked than usually assumed.

Endocrine responses to 7 days of head-down bed rest and orthostatic tests in men and women.

The objective of this study was to investigate plasma volume (PV), total body water, hormones and hydroelectrolyte responses in eight males (25-40 years) and eight females (25-31 years) during 7 days of exposure to simulated microgravity (-6 degrees head-down bed rest, HDBR). Bed rest is a model that has commonly been used to simulate spaceflight. Heart rate (HR), blood pressure (BP) and vasoactive hormone responses were studied before and after HDBR during a 10-min stand test. No change in total body water and body mass was noted in either sex. The decrease in PV was similar in both men (9.1 +/- 1.4%) and women (9.4 +/- 0.8%). Urinary normetanephrine (NMN) was decreased during HDBR in both sexes. Urinary metanephrine (MN) and plasma catecholamines were unchanged. Daily urinary excretion of urea, an indirect index of protein breakdown, was increased only in the female subjects during HDBR. Plasma active renin (AR) and aldosterone were increased in both sexes, but urinary atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were unchanged throughout the study. Also, the hormonal responses to 7 days of HDBR were comparable between men and women. Moreover, the results show similar cardiovascular and endocrine responses to standing after HDBR. However, the orthostatic intolerance following HDBR was associated with a blunted increase in noradrenaline (NA) only in the women during the stand test. It is concluded that: (i) 7 days of physical inactivity achieved during HDBR resulted in a reduced sympathetic activity in both sexes and alterations in protein metabolism in women and (ii) standing after HDBR resulted in an attenuated release of noradrenaline in women.

The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown.

The metabolic response to fasting involves a series of hormonal and metabolic adaptations leading to protein conservation. An increase in the serum level of growth hormone (GH) during fasting has been well substantiated. The present study was designed to test the hypothesis that GH may be a principal mediator of protein conservation during fasting and to assess the underlying mechanisms. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state (basal), 2) after 40 h of fasting (fast), 3) after 40 h of fasting with somatostatin suppression of GH (fast-GH), and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement (fast+GH). The two somatostatin experiments were identical in terms of hormone replacement (except for GH), meaning that somatostatin, insulin, glucagon and GH were administered for 28 h; during the last 4 h, substrate metabolism was investigated. Compared with the GH administration protocol, IGF-I and free IGF-I decreased 35 and 70%, respectively, during fasting without GH. Urinary urea excretion and serum urea increased when participants fasted without GH (urea excretion: basal 392 +/- 44, fast 440 +/- 32, fast-GH 609 +/- 76, and fast+GH 408 +/- 36 mmol/24 h, P < 0.05; serum urea: basal 4.6 +/- 0.1, fast 6.2 +/- 0.1, fast-GH 7.0 +/- 0.2, and fast+GH 4.3 +/- 0.2 mmol/1, P < 0.01). There was a net release of phenylalanine across the forearm, and the negative phenylalanine balance was higher during fasting with GH suppression (balance: basal 9 +/- 3, fast 15 +/- 6, fast-GH 17 +/- 4, and fast+GH 11 +/- 5 nmol/min, P < 0.05). Muscle-protein breakdown was increased among participants who fasted without GH (phenylalanine rate of appearance: basal 17 +/- 4, fast 26 +/- 9, fast-GH 33 +/- 7, fast+GH 25 +/- 6 nmol/min, P < 0.05). Levels of free fatty acids and oxidation of lipid decreased during fasting without GH (P < 0.01). In summary, we find that suppression of GH during fasting leads to a 50% increase in urea-nitrogen excretion, together with an increased net release and appearance rate of phenylalanine across the forearm. These results demonstrate that GH-possibly by maintenance of circulating concentrations of free IGF-I--is a decisive component of protein conservation during fasting and provide evidence that the underlying mechanism involves a decrease in muscle protein breakdown.

Pharmacokinetic Studies of [14C]Urea. (1); Absorption, Distribution, Metabolism and Excretion after Single Administration of [14C]Urea in Fasted Rats.

Absorption, distribution, metabolism and excretion after a single intravenous and oral administration of [14C]urea at a main dose of 2 mg/kg were investigated in non-fasted rats. Comparison of the pharmacokinetics in rats between under non-fasted and fasted conditions was also investigated. 1. The radioactivity levels in plasma were decreased biphasically with t1/2α of 2-3 hr and t1/2β of 6-11 hr, irrespective of administration routes and doses. After oral administration at doses of 2, 62.5, 250 and 1000 mg /kg, the Cmax and AUC0-∞ were virtually proportional to the administered doses, suggesting linear-pharmacokinetics within the examined dose range. 2. The radioactivity levels in plasma and tissues reached Cmax at 0.5-1 hr after oral administration. The concentration in the kidney, which was 2.4 times as high as that in plasma, was the highest in the examined tissues. The concentrations in other tissues were similar to, or lower than the plasma concentration. After the Cmax, the concentrations in most tissues decreased in almost parallel with the plasma concentration. 3. In plasma at 1 hr after oral administration, only the unchanged drug was observed in the plasma radioactivity. On the other hand, at 8 hr, about 70% and 30% of the plasma radioactivity were unchanged drug and unknown components, respectively. In urine for 24 hr after dosing, only the unchanged drug was also observed, irrespective of administration routes. 4. Within 96 hr, 73.1%, 1.6% and 20.1% of dosed radioactivity were excreted in urine, feces and expired air after intravenous administration, and 54.0%, 1.0% and 42.9% after oral administration, respectively. The bioavailability estimated from the ratio of urinary excretion of urea after oral administration to that after intravenous administration was 74%. 5. Feeding condition in rats enhanced metabolism/decomposition of urea and influenced its plasma concentration-time profiles and excretion profile.

Calculated nitrogen balance in hemodialysis patients: Influence of protein intake

Optimal nutrient intake is important in the maintenance of a positive nitrogen balance in hemodialysis (HD) patients. The objectives of this study were (1) to assess the influence of two levels of protein intakes on nitrogen balance in stable adult HD patients, and (2) to identify a minimum level of protein intake that would result in a negative nitrogen balance, so that preliminary recommendations may be made in Indian patients on maintenance HD (MHD). Stable, adult, nondiabetic MHD patients were recruited after informed consent into a cross over trial with a high-protein (HP) diet [1.2 g/kg ideal body weight (IBW)/day), followed by a low-protein (LP) diet (0.6 g/kg IBW/day] after appropriate periods of equilibration; for both diets, 50% of protein was of high biological value, and calorie intake was 35 kCal/kg IBW/day. Duplicate meals and residues were weighed, homogenized, and stored at -20 degrees C for analysis of dietary N by the Kjeldahl method, used to check the consistency of the N content of the diet supplied. Pre- and post- (30-minute equilibrated) blood urea samples were drawn, and details of weights and other HD parameters were recorded. Interdialytic urine collections for urea were obtained. N input came from dietary protein calculated as 16% of the weight of biological protein; N output was calculated using blood-side urea measurements and urinary urea excretion and was the sum of urea N (UN) and nonurea N (NUN) losses (assumed to be equal to 0.031 g N/kg/day). Fifteen patients were recruited. Twelve patients completed both limbs of the study. The mean age was 30.3 +/- 12.7 years. The body mass index was 18.9 +/- 2.4. Serum albumin was 3.8 +/- 0.35 g/dL, and Kt/V (equilibrated) was 1.17 +/- 0.3 g/dL. Protein consumed was 1.06 +/- 0.18 g/kg IBW/day in the HP limb versus 0.61 +/- 0.1 g/kg IBW/day in the LP limb (P = 0.000). Energy intake was 33 +/- 6.5 vs. 32.8 +/- 6. 7 kCal/kg IBW/day, respectively (P = 0.8). The normalized protein N appearance (nPNA) was 0.88 +/- 0.2 g/kg/day in the HP limb versus 0. 78 +/- 0.2 g/kg/day in the LP limb (P = 0.02). Dietary N was 73.5 +/- 15.3 g in the HP week and 42.5 +/- 7.5 g in the LP week (P = 0. 000). The difference between this and the sum of (UN + NUN) losses over the week was 29 +/- 13.2 g versus 1.2 +/- 8.1 g, respectively (P = 0.001), showing a strong, uniformly positive nitrogen balance with HP diet and neutral to negative nitrogen balance with LP diet. The ratio of dietary protein intake (DPI) to nPNA was significantly lower (anabolic) in the HP limb (0.7 +/- 0.2 vs. 1.12 +/- 0.3, P = 0. 000). On a scatter plot of nPNA to DPI, a catabolic relationship was demonstrated below a DPI of 0.75 g/kg/day (95% CI, 0.65 to 0.85 g/kg/day). A DPI of approximately 1.1 g/kg/day produces a positive nitrogen balance and 0.6 g/kg/day a neutral to negative nitrogen balance, demonstrating protein anabolism as a function of protein intake. It is suggested that a protein intake of 0.85 g/kg/day should be considered unsafe. These conclusions apply in stable nondiabetic adult HD patients in the setting of adequate dialysis and adequate calorie intake.

Nephrotic proteinuria has no net effect on total body protein synthesis: Measurements with 13C valine

In nephrotic syndrome, significant amounts of plasma proteins, mostly of hepatic origin, are lost in urine. Total hepatic protein synthesis increases, suggesting that other protein pools must be conserved to maintain steady state. This can be accomplished either by decreased amino acid oxidation or decreased protein synthesis in other organs to replace lost liver-derived proteins. To determine the effect of nephrotic syndrome on total-body protein metabolism, we compared whole-body valine use in seven nephrotic patients and five controls using a primed continuous infusion of [1-13C]-valine, with additional priming of NaH13CO3 . Plasma [13C]-valine, 13C α ketoisovaleric acid, and the expired 13CO2 enrichments were used to assess whole-body valine flux, valine oxidation, and nonoxidative valine disposal (NOVD). The valine flux into the blood compartment (97.7 ± 3.0 versus 95.3 ± 3.3 μmol/kg/h), oxidation of valine (19.4 ± 1.9 versus 21.2 ± 2.8 μmol/kg/h), and NOVD (78.3 ± 2.5 versus 74.2 ± 2.7 μmol/kg/h) were not statistically different in patients compared with controls. Valine oxidation correlated positively with urinary urea excretion (r = 0.70; P = 0.01) in all subjects. Compared with control subjects who have similar urinary urea excretion, nephrotic subjects do not compensate for urinary loss of protein by decreased amino acid oxidation or decreased nonoxidative valine disposal. Previous studies have shown that synthesis of several hepatic proteins increases when subjects are fed the same dietary regime, whereas the present study shows that total-body protein synthesis does not increase. This would imply reduced synthesis of nonhepatic protein pools.

Physiologic responses to laparoscopic aortofemoral bypass grafting in an animal model.

To measure and compare the physiologic, metabolic, and hemodynamic responses to aortofemoral bypass grafting by three techniques: open or conventional laparotomy, laparoscopic-assisted (minilaparotomy), and totally laparoscopic grafting. Twenty-four laboratory-bred hounds were randomized to one of three groups (open, laparoscopic-assisted, or totally laparoscopic). Four sets of parameters were measured: hemodynamic (intraoperative continuous cardiac output monitoring), inflammatory or hematologic (serial leukocyte and platelet levels), metabolic responses (serial blood glucose, serum cortisol and insulin, plasma epinephrine, plasma norepinephrine, and dopamine levels), and catabolic (24-hour urinary nitrogen excretion). Cardiac output increased transiently with aortic cross-clamping, more in the laparoscopic-assisted and total laparoscopic groups than in the open group, but the differences were not significant. White blood counts nearly doubled within 12 hours of surgery but were similar in all three groups. Platelet counts decreased significantly in all three groups, but no significant intergroup effects were observed. Metabolic parameters (e.g., blood glucose, cortisol, and catecholamine) rose significantly during surgery but fell to normal within 24 hours, with no important difference between groups. For the first 24 hours, urinary urea excretion fell by 50% but returned to normal by 7 days in all three groups. In the experimental animal model, the hemodynamic, hematologic, and metabolic responses to laparoscopic and laparoscopic-assisted aortofemoral bypass grafting are similar to those produced by conventional laparotomy graft placement. These data call into question whether laparoscopic techniques for aortic surgery have a significant physiologic advantage in humans.

Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis

The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs). Ninety-six ICSFs were randomly assigned a low animal protein diet (< 10% of total energy), a high-fiber diet (> 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian. At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria. These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.

Massive loss of sulfur in HIV infection.

Skeletal muscle tissue from SIV-infected macaques was previously found to contain abnormally high sulfate and low glutathione levels indicative of an excessive cysteine catabolism. We now confirm the peripheral tissue as a site of massive cysteine catabolism in HIV infection and have determined the urinary loss of sulfur per time unit. The comparison of the sulfate concentrations of the arterial and venous blood from the lower extremities of 16 symptomatic HIV+ patients and 18 HIV- control subjects (study 1) revealed (1) that the peripheral tissue of HIV+ patients with or without highly active antiretroviral therapy (HAART) releases large amounts of sulfate and (2) that plasma sulfate, thioredoxin, and interleukin-6 levels are elevated in these patients. A complementary investigation of 64 asymptomatic HIV+ patients and 65 HIV- subjects (study 2) revealed increased plasma sulfate levels in the asymptomatic patients. The analysis of the daily urinary excretion of sulfate and urea of another group of 19 HIV+ patients and 22 healthy HIV- subjects (study 3) confirmed (1) that HIV+ patients experience a massive loss of sulfur and (2) that this loss is not ameliorated by HAART. The sulfur loss of asymptomatic patients was equivalent to a mean loss of about 10 g of cysteine per day. If extrapolated, this would correspond to an alarming negative balance of approximately 2 kg of cysteine per year under the assumption that the normal sulfate excretion equivalent to approximately 3 g of cysteine per day is balanced by a standard Western diet. The abnormally high sulfate/urea ratio suggests that this process drains largely the glutathione pool.

Reproducibility and biomarker-based validity and responsiveness of a food frequency questionnaire to estimate protein intake.

This study, conducted in the Netherlands in 1994-1996, assessed the reproducibility, validity, and responsiveness of a food frequency questionnaire (FFQ) used with older subjects with type 2 diabetes. During a period of 6 months, 93 subjects had a stable protein intake according to their urinary urea excretion (UUE). An FFQ was completed before and after this period. Reproducibility was evaluated on the basis of the correlation (0.80) between duplicate FFQ estimates of protein intake. At the group level, the smallest detectable difference was 3 g. For 354 subjects, average protein intake according to the FFQ was similar to that from UUE estimates. Validity was evaluated on the basis of the crude and deattenuated correlations, which were 0.31 and 0.39, respectively. The crude correlation was highest for former smokers (r = 0.39) and for patients with a higher body mass index (r = 0.37), and it was very low for current smokers (r = 0.14, p > 0.20). The correlation did not vary with age or gender. Responsiveness was judged on the crude correlation between changes in intake according to the FFQ and UUE; the correlation was 0.22 (n = 134). The responsiveness ratio was 0.73. The authors concluded that FFQ estimates are well reproducible. At the group level, protein intake was estimated correctly, whereas individual protein intake and changes in intake were reflected to a moderate extent only.

Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure

Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality. One hundred and nine predialysis patients (age 52 +/- 1 years) with terminal CRF (glomerular filtration rate 7 +/- 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-alpha (TNF-alpha; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined. Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 +/- 0.6 vs. 13.2 +/- 0.7 mm2, P < 0.0001) and a higher prevalence of carotid plaques (72 vs. 32%, P = 0.001). The prevalence of malnutrition (SGA 2 to 4) was 44%, and 32% of all patients had an acute-phase response (CRP > or = 10 mg/liter). Malnourished patients had higher CRP levels (23 +/- 3 vs. 13 +/- 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 +/- 0.8 vs. 16.9 +/- 0.7 mm2, P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model. These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques.