Urinary Urea Excretion Research Articles

Effects of ruminal casein and glucose on forage digestion and urea kinetics in beef cattle1

Effects of supplemental glucose and degradable intake protein on nutrient digestion and urea kinetics in steers (Bos taurus) given ad libitum access to prairie hay (4.7% CP) were quantified. Six ruminally and duodenally cannulated steers (initial BW 391 kg) were used in a 4 × 4 Latin square with 2 extra steers. Treatments were arranged as a 2 × 2 factorial and included 0 or 1.2 kg of glucose and 240 or 480 g of casein dosed ruminally once daily. Each period included 9 d for adaptation, 4 d for total fecal and urine collections, and 1 d for ruminal and duodenal sampling. Jugular infusion of (15)N(15)N-urea with measurement of enrichment in urine was used to measure urea kinetics. Glucose reduced forage intake by 18% (P < 0.01), but casein did not affect forage intake (P = 0.69). Glucose depressed (P < 0.01) total tract NDF digestion. Glucose supplementation decreased ruminal pH 2 h after dosing, but the effect was negligible by 6 h (treatment × time; P = 0.01). Providing additional casein increased the ruminal concentration of NH(3), but the increase was less when glucose was supplemented (casein × glucose; P < 0.01). Plasma urea-N was increased (P < 0.01) by additional casein but was reduced (P < 0.01) by glucose. Microbial N flow to the duodenum and retained N increased (P ≤ 0.01) as casein increased, but neither was affected by glucose supplementation. Urea-N entry rate increased (P = 0.03) 50% with increasing casein. Urinary urea-N excretion increased (P < 0.01) as casein increased. The proportion of urea production that was recycled to the gut decreased (P < 0.01) as casein increased. Glucose supplementation decreased (P < 0.01) urinary urea excretion but did not change (P ≥ 0.70) urea production or recycling. The amount of urea-N transferred to the gut and captured by ruminal microbes was less for steers receiving 480 g/d casein with no glucose than for the other 3 treatments (casein × glucose interaction, P = 0.05), which can be attributed to an excess of ruminally available N provided directly to the microbes from the supplement. Overall, the provision of supplemental glucose decreased forage intake and digestibility. Increasing supplemental casein from 240 to 480 g/d increased urea production but decreased the proportion of urea-N recycled to the gut.

Relationship of whole body nitrogen utilization to urea kinetics in growing steers1

Urea kinetics were measured in 2 experiments, with treatments designed to change protein deposition by the animal. Our hypothesis was that increased protein deposition by cattle (Bos taurus) would reduce urea production and recycling to the gastrointestinal tract. Urea kinetics were measured by continuous intravenous infusion of (15)N(15)N-urea followed by measurement of enrichment in urinary urea at plateau. In Exp. 1, 6 steers (139 kg) were maintained in a model in which leucine was the most limiting AA. Treatments were arranged as a 2 × 3 factorial and were provided to steers in a 6 × 6 Latin square design. Leucine treatments included 0 or 4 g/d of abomasally supplemented L-leucine, and energy treatments included control, abomasal glucose infusion (382 g DM/d), or ruminal VFA infusion (150 g/d of acetic acid, 150 g/d of propionic acid, and 50 g/d of butyric acid). Leucine supplementation increased (P < 0.01) N retention, and energy supplementation tended to increase (P = 0.09) N retention without differences between glucose and VFA supplements (P = 0.86). Energy supplementation did not strikingly improve the efficiency of leucine utilization. Although both leucine and energy supplementation reduced urinary urea excretion (P ≤ 0.02), treatments did not affect urea production (P ≥ 0.34) or urea recycling to the gut (P ≥ 0.30). The magnitude of change in protein deposition may have been too small to significantly affect urea kinetics. In Exp. 2, 6 steers (168 kg) were maintained in a model wherein methionine was the most limiting AA. Steers were placed in 2 concurrent 3 × 3 Latin squares. Steers in one square were implanted with 24 mg of estradiol and 120 mg trenbolone acetate, and steers in the other square were not implanted. Treatments in each square were 0, 3, or 10 g/d of L-methionine. Implantation numerically improved N retention (P = 0.13) and reduced urea production rate (P = 0.03), urinary urea excretion (P < 0.01), and urea recycling to the gastrointestinal tract (P = 0.14). Effects of methionine were similar to implantation, but smaller in magnitude. When protein deposition by the body is increased markedly, ruminally available N in the diet may need to be increased to offset reductions in urea recycling.

A review of factors influencing milk urea concentration and its relationship with urinary urea excretion in lactating dairy cattle

SUMMARYMilk urea nitrogen (MUN) concentration in dairy cows may serve as an on-farm indicator to guide nutritional strategies and to help reduce emissions of nitrogen (N) to the environment. Excretion of urinary urea nitrogen (UUN) is positively related to MUN, but the relationship is highly variable. The accuracy of MUN as a predictor of UUN may improve when various factors that affect this relationship can be taken into account. The current review discusses the impact of a number of UUN : MUN ratio influencing factors related to: physiological mechanisms in the dairy cow, farm management, differences between individual cows, nutrition and analysis methods for MUN. Factors related to variation in water intake, urine production, dietary protein level, body weight (BW) and time and frequency of feeding and milking are shown to affect MUN and its relationship with UUN. In addition, a number of factors are discussed that are likely to affect this relationship such as biological rhythm, renal reabsorption of urea during periods of protein deficiency and breeding value for MUN. Accounting for these above-mentioned factors in the relationship between MUN and UUN might substantially improve the applicability and accuracy of MUN as a predictor of protein utilization efficiency and UUN.

Protective Effect of Heat-processed Ginseng (Sun Ginseng) in the Adenine-induced Renal Failure Rats

The effect of orally administered sun ginseng (SG), which is a ginseng processed by steaming, was examined in adenine-induced chronic renal failure rat. SG significantly decreased both blood urea nitrogen and serum creatinine levels, indicating an improvement of renal function. Also, SG significantly increased the urinary excretion of both urea and creatinine. Furthermore it lowered the blood pressure, and inhibited adenine-induced kidney hypertrophy and edema. Based on these findings, SG may ameliorate chronic renal failures.

DIETARY PROTEIN INTAKE IS INDEPENDENTLY ASSOCIATED WITH THE URINARY EXCRETION OF PHOSPHATE

Decrease of urinary phosphate (P) excretion and P retention triggers activation of phosphotonins and subsequent development of secondary hyperparathyroidism in progressing of chronic kidney disease (CKD). The main source of P is dietary protein. No large studies are presented to-date to evaluate the relationship between dietary protein intake and parameters of P metabolism in CKD patients. This was a goal of the cross-sectional cohort study .11315 CKD patients were entered (males 43%). Median (10th-90th percentile) of age and estimated glomerular filtration rate (GFR) were 46 (24-69) and 64 (24-104). The analyzed data were: age, gender, body mass index (BMI) serum albumin, creatinine, calcium and phosphate; 24-h urine creatinine, phosphate (P),proteinuria (DP). Estimated parameters includes: eGFR, fractional P excretion (FEP), 24-h P excretion (24-h UP), and P clearance (CP). Dietary protein intake (DPI) was based on 24-h urinary urea excretion. No significant differences in serum phosphate were found in groups with various DPI. FEP, 24-h UP and CP were significantly higher in higher DPI range. DPI was positively associated with 24-h UP ( β =0,287, p <0.000001) in multivariate model adjusted for age, gender, DP, eGFR, serum P, FEP, BMI, and Ca. Thus, DPI is considered to be the independent factor influencing urinary P excretion and hence contributing to progression of mineral and bone disease in renal dysfunction.

Protein abundance of urea transporters and aquaporin 2 change differently in nephrotic pair-fed vs. non-pair-fed rats

Salt and water retention is a hallmark of nephrotic syndrome (NS). In this study, we test for changes in the abundance of urea transporters, aquaporin 2 (AQP2), Na-K-2Cl cotransporter 2 (NKCC2), and Na-Cl cotransporter (NCC), in non-pair-fed and pair-fed nephrotic animals. Doxorubicin-injected male Sprague-Dawley rats (n = 10) were followed in metabolism cages. Urinary excretion of protein, sodium, and urea was measured periodically. Kidney inner medulla (IM), outer medulla, and cortex tissue samples were dissected and analyzed for mRNA and protein abundances. At 3 wk, all doxorubicin-treated rats developed features of NS, with a ninefold increase in urine protein excretion (from 144 ± 21 to 1,107 ± 165 mg/day; P < 0.001) and reduced urinary sodium excretion (from 0.17 to 0.12 meq/day; P < 0.001). Urine osmolalities were reduced in the nephrotic animals (1,057 ± 37, treatment vs. 1,754 ± 131, control). Unlike animals fed ad libitum, UT-A1 protein abundance was unchanged in nephrotic pair-fed rats. Glycosylated AQP2 was reduced in the IM base of both nephrotic groups. Abundances of NKCC2 and NCC were consistently reduced (71 ± 7 and 33 ± 13%, respectively) in both nephrotic pair-fed animals and animals fed ad libitum. In pair-fed nephrotic rats, we observed an increase in the cleaved form of membrane-bound γ-epithelial sodium channel (ENaC). However, α- and β-ENaC subunits were unaltered. NKCC2 and AQP2 mRNA levels were similar in treated vs. control rats. We conclude that dietary protein intake affects the response of medullary transport proteins to NS.

Magnesium intervention and blood pressure—A study on risk groups

Hypothesis: Although mineral deficiency in particular magnesium is a known risk factor for cardiovascular disease intervention experiments with magnesium show only modest results. Previously published data suggest that there may be particular risk groups in the population. The study was undertaken to investigate if such risk groups could be identified. Experimental design: Subjects (n = 31) were 50 - 79 years old with no disease. The 24 hour urinary excretion of urea (proxy for acidity), magnesium, calcium, and potassium was measured at two week intervals, with and without intervention with mineral water. Intervention with mineral water comprised 75 mL daily, supplying 3.1 mmol Mg, 2.3 Ca, and 0.02 K. Major results: There was a significant relation between acidity and excretion of magnesium, calcium, and potassium, both at one occasion and regarding changes over time. Among subjects with a high secretion of urea there was an inverse relation between the excretion of magnesium and systolic blood pressure. After intervention with mineral water, there was a strong tendency to a decrease in the systolic blood pressure among those with an initial high excretion of urea and a low excretion of magnesium. Conclusions: The results demonstrate the importance of acid-base conditions for mineral homeostasis and suggest the presence of risk groups in the population, related either to a low intake or to a disorder in the reabsorbtion mechanisms. Mineral water decreased the systolic blood pressure in that particular risk group.

Effect of methanolic fraction of Kalanchoe crenata on metabolic parameters in adriamycin-induced renal impairment in rats

Objectives:To investigate the effect of Kalanchoe crenata methanolic fraction (MEKC) on proteinuria, glucosuria, and some other biochemical parameters in adriamycin-induced renal impairment in rats.Materials and Methods:Ether anesthetized rats received three intravenous injections (days 0, 14, and 28) of 2 mg/kg body weight of adriamycin. Repeated doses of the extract (0, 50, and 68 mg/kg b.w.) and losartan (10 mg/kg b.w.) were administered orally once daily, for 6 weeks, to these rats. Kidney functions were assessed through biochemical parameters.Results:MEKC decreased proteinuria and also the urinary excretion of creatinine, glucose, and urea significantly in diseased rats. A decrease in serum levels of creatinine, urea, potassium, alkaline phosphatase, conjugate bilirubin, and alanine transaminase level was also recorded in nephropathic rats, but plasma levels of uric acid and glucose remained unchanged. Moreover, the plant extract markedly (P < 0.05) increased plasma sodium and decreased (P < 0.01) the urinary sodium and potassium levels.Conclusions:The results indicated that the treatment with the methanolic fraction of K. crenata may improve proteinuria and all other symptoms due to adriamycin-induced nephropathy and, more than losartan, could ameliorate kidney and liver functions. K. crenata could be a potential source of new oral antinephropathic drug.

Nitrogen metabolism and recycling in yaks (Bos grunniens) offered a forage - concentrate diet differing in N concentration

An experiment was conducted to characterise N use efficiency and quantify urea fluxes in yaks offered four levels of dietary N (1.43%, 1.97%, 2.45% and 2.90% of diet DM) in a 4 × 4 Latin square design. The incremental increase in N intake linearly increased N retention (P = 0.003) and the excretion of urinary N (P &lt; 0.001), but no difference (P &gt; 0.05) in faecal N excretion was observed in growing yaks fed any of the four diets. Microbial N production had quadratic (P &lt; 0.001) responses to dietary N, characterised by the highest microbial N production occurring in the 1.97% N diet (P &lt; 0.05). As the N content of the diet increased, the urinary excretion of urea increased from 13% to 27% of urea entry rate (quadratic, P &lt; 0.001), whereas gastrointestinal entry urea returned to ornithine cycling decreased from 46% to 40% (linear, P &lt; 0.001), and the gastrointestinal entry urea used for anabolism increased from 50% to 56% (linear, P &lt; 0.001). Gastrointestinal entry urea incorporated into bacterial N decreased linearly (P &lt; 0.001) with incremental increase in N intake, and the greatest concentration (23.5%) of bacterial N originating from plasma urea N was in yaks fed the 1.43% N diet. As much as 87% of the urea synthesised in the liver was returned to the gastrointestinal tract when the yaks were fed a diet with 1.43% N (1.1 times the maintenance N level). Moreover, constantly greater urea production than the intake of digestible N, and the gastrointestinal-urea clearance than the kidney-urea clearance were observed, respectively, in the growing yaks, regardless of the level of N intake. These results suggest that yaks might be more efficient at utilising N under harsh environment than are cattle.

Collecting duct-specific knockout of adenylyl cyclase type VI causes a urinary concentration defect in mice

Collecting duct (CD) adenylyl cyclase VI (AC6) has been implicated in arginine vasopressin (AVP)-stimulated renal water reabsorption. To evaluate the role of CD-derived AC6 in regulating water homeostasis, mice were generated with CD-specific knockout (KO) of AC6 using the Cre/loxP system. CD AC6 KO and controls were studied under normal water intake, chronically water loaded, or water deprived; all of these conditions were repeated in the presence of continuous administration of 1-desamino-8-d-arginine vasopressin (DDAVP). During normal water intake or after water deprivation, urine osmolality (U(osm)) was reduced in CD AC6 KO animals vs. controls. Similarly, U(osm) was decreased in CD AC6 KO mice vs. controls after water deprivation+DDAVP administration. Pair-fed (with controls) CD AC6 KO mice also had lower urine osmolality vs. controls. There were no detectable differences between KO and control animals in fluid intake or urine volume under any conditions. CD AC6 KO mice did not have altered plasma AVP levels vs. controls. AVP-stimulated cAMP accumulation was reduced in acutely isolated inner medullary CD (IMCD) from CD A6 KO vs. controls. Medullary aquaporin-2 (AQP2) protein expression was lower in CD AC6 KO mice vs. controls. There were no differences in urinary urea excretion or IMCD UT-A1 expression; however, IMCD UT-A3 expression was reduced in CD AC6 KO mice vs. controls. In summary, AC6 in the CD regulates renal water excretion, most likely through control of AVP-stimulated cAMP accumulation and AQP2.

Effect of forage source and a supplementary methionine hydroxy analog on nitrogen balance in lactating dairy cows offered a low crude protein diet

Four primiparous and 4 multiparous midlactation dairy cows were stratified by pre-experimental milk yield (23.5±2.3kg/d), protein yield (0.75±0.066kg/d), parity, and days in lactation (121±10 d) into 4 groups of 2 in a 2×2 factorial, Latin square design (n=8) to assess the effect of forage source and a supplementary methionine hydroxy analog on nitrogen (N) balance where low crude protein (CP) diets (13.3%) are offered. Diets contained either predominantly grass silage [GS (G− and G+)] or corn silage [CS (C− and C+)] as the forage source and were offered with (G+ and C+) or without (G− and C−) the isopropyl ester of 2-hydroxy-4 methylthio butanoic acid (HMBi). The G− and G+ contained 46% GS and 10% CS in the dry matter (DM), whereas C− and C+ contained 12% GS and 52% CS in the DM. Supplementary HMBi was included at a rate of 0.2% of DM in G+ and C+ diets. Diets were isonitrogenous (9.8±0.4% protein truly digested in the small intestine) and isoenergetic (0.96±0.01 units of energy for lactation; kg/DM). Each of the 4 experimental periods lasted 24 d: 14 d for dietary adaptation, followed by 10 d of housing in individual metabolism stalls; N balance was conducted on the last 5 d of each experimental period. Intake of DM was higher for CS-based vs. GS-based diets (20.23 vs. 18.41kg/d). No effect of dietary treatment was found on milk yield or yields of milk fat, protein, and lactose. Supplementing with HMBi tended to improve milk solids yield (1.69 vs. 1.59kg/d), casein yield (0.59 vs. 0.55kg/d), and concentrations of casein (2.89 vs. 2.73%) and protein (3.58 vs. 3.49%) in the milk. Dietary N intake was higher for CS-based vs. GS-based diets (0.460 vs. 0.422kg/d). However, forage source or supplementary HMBi had no effect on N excretion in the feces, urine, or milk. Excretion of urinary urea was positively related to N intake. Concentrations of urea N in the plasma (2.34 vs. 1.72mmol/L), milk (2.54 vs. 2.24mmol/L), and urine (123.32 vs. 88.79mmol/L), and total excretion of urinary urea N (40.23 vs. 35.09g/d) were higher for animals offered CS-based vs. GS-based diets. Corn silage improved N intake through improved DM intake. However, neither forage source nor HMBi supplementation affects N output in the feces, urine, or milk.

Condensed Tannin in Drinking Water Reduces Greenhouse Gas Precursor Urea in Sheep and Cattle Urine

Abstract Ingestion of small amounts of condensed tannin (CT) by ruminants may provide benefits including reduction of ammonia and nitrous oxide emissions by reducing urine urea excretion. However, providing grazing ruminants with sufficient amounts of CT-containing forages is difficult, and an alternative may be to provide CT in their drinking water. We conducted three trials to determine if urine urea levels in sheep and cattle decrease after they drink water containing CT. In two initial trials, blood serum urea was measured as a surrogate for urine urea when lambs or steers drank tap water containing low to higher amounts of quebracho tannin (QT). Serum urea concentration was measured after lambs drank the treatments for 7 d or steers for 4–6 d. Lambs consumed pellets (16% crude protein [CP] as fed) at 3.5% of body weight, and steers were fed cubes (15% CP as fed) at 3% of body weight. Mean serum urea concentration in sheep was reduced when they consumed water with QT ( P = 0.03) and was also reduced for cattle ( P P = 0.03). Reductions in daily urea excretion as a percentage of nitrogen intake were 3.5%, 6.6%, and 12.6%, respectively, for the low, medium, and high QT intake. Small amounts of QT in the drinking water of grazing ruminants can reduce their urine urea excretion.

Butyrate regulates urea metabolism and nitrogen use in sheep

Butyrate has been implicated in regulation of rumen urea transporter expression and thus urea recycling, yet direct evidence is absent. This study aimed to determine the effect of butyrate on urea recycling by infusion of butyrate into the rumen. Wether sheep (42 kg BW) fitted with rumen cannula were fed to 1.8× energy maintenance a standard diet (130 g CP/kg, 9.3 MJ ME/kg) and infused into the rumen with isoenergetic (1.2 MJ/d) and isonatremic solutions of either Na‐Acetate (control) or Na‐Butyrate for 10‐d periods in a crossover design. [15N2]Urea was continuously infused IV for the last 5 d, and all urine and feces were collected. Compared to no infusion, Butyrate increased (P &lt; 0.05) rumen acetate and butyrate, whereas Acetate increased (P &lt; 0.05) rumen acetate. Compared to Acetate, Butyrate decreased urea entry (17.2 vs 14.3 g urea‐N/d, P &lt; 0.05) and urinary urea excretion (9.3 vs 7.7 g urea‐N/d, P = 0.11). Although transfer of urea to the gut was not different, Butyrate increased (0.6 vs 2.2 g urea‐N/d, P &lt; 0.05) microbial capture of the urea‐N that was transferred to the gut. The results suggest that butyrate does not increase urea recycling to the gut compared to acetate. However, the reduction in urea synthesis coupled with increased capture of recycled urea‐N by gut microbes suggests that butyrate enhanced overall capture of feed and urea derived ammonia by microbes. Supported by Maryland Agricultural Experiment Station.

Effect of feeding different sources of rumen-protected methionine on milk production and N-utilization in lactating dairy cows

Objectives of this study were to quantify production responses of lactating dairy cows to supplying absorbable Met as isopropyl-2-hydroxy-4-(methylthio)-butanoic acid (HMBi), or rumen-protected Met (RPM, Smartamine M; Adisseo, Alpharetta, GA) fed with or without 2-hydroxy-4-(methylthio)-butanoic acid (HMB), and to determine whether Met supplementation will allow the feeding of reduced dietary crude protein (CP). Seventy cows were blocked by parity and days in milk into 14 blocks and randomly assigned within blocks to 1 of the 5 dietary treatments based on alfalfa and corn silages plus high-moisture corn: 1 diet with 15.6% CP and no Met source (negative control); 3 diets with 15.6% CP plus 0.17% HMBi, 0.06% RPM + 0.10% HMB, or 0.06% RPM alone; and 1 diet with 16.8% CP and no Met supplement (positive control). Assuming that 50% of ingested HMBi was absorbed from the gastrointestinal tract and 80% of the Met in RPM was absorbed at intestine, the HMBi and RPM supplements increased metabolizable Met supply by 9g/d and improved the Lys:Met ratio from 3.6 to 3.0. After a 2-wk covariate period during which all cows received the same diet, cows were fed test diets continuously for 12 wk. Diet did not affect dry matter intake (mean ± SD, 25.0±0.3kg/d), body weight gain (0.59±0.2kg/d), or milk yield (41.7±0.6kg/d). However, feeding HMBi increased yield of energy-corrected milk and milk content of protein and solids-not-fat. Moreover, trends were observed for increased milk fat content and yield of fat and true protein on all 3 diets containing supplemental Met. Apparent N efficiency (milk N/N intake) was highest on the RPM treatment. Feeding 16.8% CP without a Met source elevated milk urea N and urinary excretion of urea N and total N and reduced apparent N efficiency from 34.5 to 30.2%, without improving production. Overall results suggested that feeding HMBi or RPM would give similar improvements in milk production and N utilization.

Effect of the Quality of Dietary Amino Acids Composition on the Urea Synthesis in Rats

We have shown that urinary urea excretion increased in rats given a lower quality protein. The purpose of present study was to determine whether the composition of dietary amino acids affects urea synthesis. Experiments were done on three groups of rats given diets containing a 10% gluten amino acid mix diet or 10% casein amino acid mix diet or 10% whole egg protein amino acids mix diet for 10 d. The urinary excretion of urea, the liver concentration of N-acetylglutamate, and the liver concentration of free serine, glutamic acids and alanine were greater in the group given the amino acid mix diet of lower quality. The fractional and absolute rates of protein synthesis in tissues declined with a decrease in quality of dietary amino acids. The hepatic concentration of ornithine and the activities of hepatic urea-cycle enzymes were not related to the urea excretion. These results suggest that the increased concentrations of amino acids and N-acetylglutamate seen in the liver of rats given the amino acid mix diets of lower quality are likely among the factors stimulating urea synthesis. The protein synthesis in tissues is at least partly related to hepatic concentrations of amino acids. The composition of dietary amino acids is likely to be one of the factors regulating urea synthesis when the quality of dietary protein is manipulated.

High sodium and low potassium intake in patients with Type 2 diabetes

To document dietary sodium and potassium intake and adherence to the Australian National Heart Foundation (NHF) guidelines in patients with Type 2 diabetes mellitus attending an Australian tertiary referral and university teaching hospital. In a longitudinal study, 24h urinary sodium (uNa), potassium (uK), creatinine (uCr), urea (uUrea) and glucose (uGlu) excretions, urine volume (uVol) and body mass index were recorded in 122 regular attenders over an 8 year period (2001-2008; mean of 1.9 samples/patient/year). In a cross-sectional study, the same measurements were recorded in patients providing urine samples in the month of June from 2001 to 2009 (782 patients, averaging 87/year). In the longitudinal study, uNa (mmol/24 h) was 170 ± 53 (mean ± SD) in males and 142 ± 51 in females, whereas uK (mmol/24 h) was 75 ± 22 in males and 62 ± 18 in females. Once adjusted for insensible losses, only 3% of males and 14% of females met the NHF dietary sodium intake guidelines, and 14% of males and 3% of female patients met the NHF dietary potassium guidelines. Body mass index, uUrea, uVol and uGlu were independent predictors of uNa (adjusted r(2) =0.57, P<0.0001). The mean intra-individual coefficient of variation of the corrected uNa was 21 ± 1%. The cross-sectional study confirmed these findings, and no temporal trends were observed. There was no correlation with glycated haemoglobin to suggest natriuresis with hyperglycaemia. Most patients with Type 2 diabetes mellitus do not meet NHF sodium or potassium intake guidelines. A diet high in sodium and low in potassium may contribute to the development of hypertension and to resistance to blood-pressure-lowering therapies.

Copeptin, a Surrogate Marker of Vasopressin, Is Associated with Disease Severity in Autosomal Dominant Polycystic Kidney Disease

Experimental studies suggest a detrimental role for vasopressin in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, it is unknown whether endogenous vasopressin concentration is associated with disease severity in patients with ADPKD. Plasma copeptin concentration (a marker of endogenous vasopressin levels) was measured in 102 ADPKD patients (diagnosis based on Ravine criteria) by an immunoassay. Plasma and urinary osmolarity were also measured. To assess disease severity, GFR and effective renal blood flow were measured by continuous infusion of 125I-iothalamate and 131I-hippuran, total renal volume by magnetic resonance imaging, and 24-hour urinary albumin excretion by nephelometry. In these ADPKD patients, copeptin was associated with the various markers of disease severity in ADPKD (positively with total renal volume [R=0.47] and albuminuria [R=0.39] and negatively with GFR [R=-0.58] and effective renal blood flow [R=-0.52], all P<0.001). These associations were independent of age, gender, and use of diuretics. Copeptin was furthermore associated with plasma osmolarity (P<0.001) but not with 24-hour urinary volume, 24-hour urinary osmolarity or fractional urea excretion (P=0.7, 0.9, and 0.3, respectively). On cross-sectional analysis, copeptin is associated with disease severity in ADPKD patients, supporting the results of experimental studies that suggest that vasopressin antagonists have a renoprotective effect in ADPKD and offering a good prospect for clinical studies with these agents.

Estimating fermentative amino acid losses in the upper gut of pigs

Fermentative catabolism of dietary and endogenous amino acids (AA) in the upper gut of pigs (FAAC) can result in significant loss of AA available for protein synthesis and body maintenance functions. A continuous infusion trial was performed using isotope tracers to determine ammonia flux in the upper gut, whole body urea flux, urea recycling (urea flux − urinary urea excretion), and FAAC (ammonia flux in the upper gut − urea recycling) in ileal-cannulated growing pigs fed a control diet (C, 19.3% CP), the control diet with added fibre (F, 12% pectin added at expense of cornstarch), or a diet low in protein (LP, 13.6% CP). 15N-ammonium chloride and 13C-urea were infused intragastrically and intravenously, respectively, for a period of 4 days. In samples obtained on days 3 and 4 of infusion, 15N-enrichments in blood urea (6.21 ± 1.65, 8.93 ± 2.01, and 9.78 ± 1.40 atoms percent excess (APE) for C, F and LP, respectively) were higher than those in ileal ammonia (0.44 ± 0.12, 0.37 ± 0.14, and 0.71 ± 0.10 APE). This suggests a rapid absorption of ammonia prior to the distal ileum and lack of uniformity for enrichment in the digesta ammonia pool. Simple isotope dilution calculations are, therefore, inadequate for calculating FAAC and ammonia flux in the upper gut of pigs. A two compartment (ileal ammonia and plasma urea) model was developed to determine possible value ranges for FAAC in the upper gut (0.0 to 13.3 ± 1.42, 15.5 ± 1.65, and 10.7 ± 1.20 mmol N/kg/d for the three treatments), but this model also has limitations. Quantifying FAAC in the upper gut of pigs offers a number of challenges, but warrants further investigation.

Assessing the effects of low dose aspirin on uricacid and renal function in healthy adults

Objective: To evaluate the effects of low daily aspirin doses on uric acid (UA) level and renal functions in healthy adults. Methods: Healthy adults were randomized to receive 100 mg (n= 33), or 300 mg (n = 31) aspirin daily for one month. Laboratory tests included measurement of blood urea nitrogen (BUN), serum creatinine, and uric acid (UA) levels. Urine creatinine, urea and uric acid excretion were measured in a 24 h collection of urine, 24 hours urine uric acid, creatinine clearance (Ccr), were measured at baseline and then after 4 weeks of therapy. Results: After 4 weeks of therapy, 100 and 300 mg/d dosage, aspirin caused a 7% and 12% decrease in the rate of UA excretion respectively (P< 0.05). Patients at the dosage 300 mg/d but not the 100mg/day had an increase in serum levels of uric acid (UA), creatinine and urea with a significant decrease in 24 hour creatinine clearance and urinary urea excretion (P<0.05) when compared with the baseline. Conclusion: Because of the effects of 300 mg dose aspirin, in the lowering of kidney function and the potential of aspirin to cause dose-dependent impairment of renal function, patients taking low-dose aspirin therapy should be monitored for the development of impaired renal function.

Acid-base conditions regulate calcium and magnesium homeostasis

Previous experimental studies demonstrate that the acid-base balance influences mineral homeostasis by regulating the absorption of calcium and magnesium in the kidneys. No intervention studies are available on population samples. To study the urinary excretion of calcium and magnesium before and after an intervention with the aim of decreasing the acid load. Healthy subjects aged 50-75 years were recruited by advertising. Urinary calcium, magnesium and urea as well as blood pressure were measured before and after the intervention. This comprised taking tablets containing potassium hydrogen carbonate or potassium chloride (placebo) during 7-10 days. There were significant relationships between the urinary excretion of urea and magnesium and calcium before the intervention. Comparing before and after intervention, the change in urinary excretion of urea was related to a change in urinary excretion of calcium and magnesium. There was a significant decrease in systolic as well as diastolic blood pressure both after administration of potassium hydrogen carbonate and citrate. The results confirm previous studies showing a relation between acid conditions in the body and the excretion of calcium and add new data on magnesium. A blood pressure decrease after potassium has been found in previous studies. This suggests an alternative for the treatment of moderately increased levels of blood pressure that should be further explored.