Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury.

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.

Nephroprotective effects of Datura metel extract in gentamicin induced mice model: biochemical and histological evidences.

Datura metel is traditionally used as a remedy for renal toxicity. However, the nephroprotection has not been scientifically validated yet. To evaluate the nephroprotective like effect of methanolic extract of D. metel in gentamicin induced mice model, mice of either sex were divided into groups. One group received normal saline as negative control. The 2nd group received gentamicin 100mg/kg for 8 days as positive control, 3rd group received 50mg/kg silymarin as standard, while the reaming groups received 100, 200 and 300 mg/kg of MEDM and gentamicin 100mg/kg, for 8 days. The blood and urine samples were collected on 9th day, animals were then dissected and whole kidneys were removed and preserved in formalin for later histological examinations. The level of serum creatinine, blood urea nitrogen, urine creatinine and urine urea were significantly (P<0.05) elevated and the renal MDA level was also elevated significantly (P<0.05) by gentamicin in mice. After the treatment of test animals with MEDM, the elevated level of serum and urine biomarkers by gentamicin were reversed by MEDM. The nephroprotective effect was found in dose dependent manner. As the MEDM significantly protected the nephrotoxicity via its antioxidant effect. The findings of our study thus proved the scientific background for the nephroprotective effect of MEDM.

The role of urea-induced osmotic diuresis and hypernatremia in a critically ill patient: case report and literature review / O papel da diurese osmótica induzida por ureia na geração de hipernatremia no paciente crítico: relato de caso e revisão da literatura

Abstract Hypernatremia is a common electrolyte problem at the intensive care setting, with a prevalence that can reach up to 25%. It is associated with a longer hospital stay and is an independent risk factor for mortality. We report a case of hypernatremia of multifactorial origin in the intensive care setting, emphasizing the role of osmotic diuresis due to excessive urea generation, an underdiagnosed and a not well-known cause of hypernatremia. This scenario may occur in patients using high doses of corticosteroids, with gastrointestinal bleeding, under diets and hyperprotein supplements, and with hypercatabolism, especially during the recovery phase of renal injury. Through the present teaching case, we discuss a clinical approach to the diagnosis of urea-induced osmotic diuresis and hypernatremia, highlighting the utility of the electrolyte-free water clearance concept in understanding the development of hypernatremia.

Resumo A hipernatremia é um distúrbio eletrolítico comum no ambiente de terapia intensiva, com uma prevalência que pode chegar a 25%. Está associada a maior tempo de internação hospitalar e é um fator de risco independente para a mortalidade. Este relato ilustra um caso de hipernatremia de origem multifatorial no ambiente de terapia intensiva. Destacaremos o papel da diurese osmótica por geração excessiva de ureia, uma causa de hipernatremia pouco conhecida e subdiagnosticada. Este cenário pode estar presente em pacientes em uso de elevadas doses de corticoides, com sangramento gastrointestinal, em uso de dietas e suplementos hiperproteicos e estado de hipercatabolismo, especialmente durante a fase de recuperação de injúria renal. A seguir, discutiremos uma abordagem clínica para o diagnóstico da hipernatremia secundária à diurese osmótica induzida por ureia, destacando a importância do conceito de clearance de água livre de eletrólitos nesse contexto.

Protective effects of spirulina against hemato-biochemical alterations, nephrotoxicity, and DNA damage upon lead exposition.

The current study was aimed at exploring the protective efficacy of spirulina against the hemato-biochemical alterations and nephrotoxicity induced by lead (Pb). Female rats aged 12 weeks were treated for 4 weeks with Pb (0.344 g kg-1 bw) associated or not with spirulina (5.3 g kg-1 bw). Renal damage induced by Pb was related to a severe anemia, increases of oxidative stress-related parameters (thiobarbituric acid reactive substances (TBARS) (+29%), protein carbonyl (PCO) (+66.3%), and advanced oxidation protein product (AOPP) (+110%)), plasma lactate dehydrogenase (LDH) (+80%), creatinine and urea levels in plasma, and uric acid concentration in urine, as well as genotoxic changes (+89.3% and +60% for DNA and mRNA levels, respectively). Conversely, LDH and antioxidant enzyme activities in kidney were decreased, as well as the levels of plasma uric acid, and urinary creatinine and urea levels. Spirulina-supplemented rats exhibited normal peripheral blood and renal parameters and renal histology. It can be suggested that Arthrospira platensis alleviates damages induced by Pb, thanks to its high phenolic content and antioxidant capacity.

The role of urea-induced osmotic diuresis and hypernatremia in a critically ill patient: case report and literature review.

Hypernatremia is a common electrolyte problem at the intensive care setting, with a prevalence that can reach up to 25%. It is associated with a longer hospital stay and is an independent risk factor for mortality. We report a case of hypernatremia of multifactorial origin in the intensive care setting, emphasizing the role of osmotic diuresis due to excessive urea generation, an underdiagnosed and a not well-known cause of hypernatremia. This scenario may occur in patients using high doses of corticosteroids, with gastrointestinal bleeding, under diets and hyperprotein supplements, and with hypercatabolism, especially during the recovery phase of renal injury. Through the present teaching case, we discuss a clinical approach to the diagnosis of urea-induced osmotic diuresis and hypernatremia, highlighting the utility of the electrolyte-free water clearance concept in understanding the development of hypernatremia.

Dietary supplementation of rumen-protected methionine decreases the nitrous oxide emissions of urine of beef cattle through decreasing urinary excretions of nitrogen and urea.

BACKGROUND: Two consecutive trials were carried out to study the effects of dietary supplementation of rumen-protected methionine (RPM) on nutrient digestibility, nitrogen (N) metabolism (Trial 1), and consequently the nitrous oxide (N2 O) emissions from urine in beef cattle (Trial 2). Eight 24-month-old castrated Simmental bulls with liveweights of 494 ± 28 kg, and four levels of dietary supplementation of RPM at 0, 10, 20, and 30 g head-1 d-1 , were allocated in a replicated 4 × 4 Latin square for Trial 1 and the N2 O emissions from the urine samples collected in Trial 1 were measured using a static incubation technique in Trial 2. RESULTS: Supplementation of RPM at 0, 10, 20, and 30 g head-1 d-1 to a basal ration deficient in methionine (Met) did not affect the apparent digestibility of dry matter, organic matter, neutral detergent fiber, or acid detergent fiber (P > 0.05), but decreased the urinary excretions of total N (P < 0.05) and urea (P < 0.001), increased the ratio of N retention / digested N (P < 0.05) in beef cattle, and decreased the estimated cattle urine N2 O-N emissions by 19.5%, 23.4%, and 32.6%, respectively (P < 0.001). CONCLUSION: Supplementation of RPM to Met-deficient rations was effective in improving the utilization rate of dietary N and decreasing the N2 O emissions from urine in beef cattle. © 2019 Society of Chemical Industry.

Roflumilast, a phosphodiesterase 4 inhibitor, attenuates cadmium-induced renal toxicity via modulation of NF-κB activation and induction of NQO1 in rats.

OBJECTIVE: In the present study, the protective effect of Roflumilast (ROF, a selective phosphodiesterase (PDE-4) inhibitor) was investigated against cadmium (Cd)-induced nephrotoxicity in rats. METHODS: A total of 24 rats were selected and randomly divided into four groups ( n = 6). Group 1 served as the control; groups 2-4 administered with CdCl2 (3 mg/kg, i.p.) for 7 days; groups 3 and 4 were co-administered with ROF in doses of 0.5 and 1.5 mg/kg, orally for 7 consecutive days. Nephrotoxicity was evaluated by measuring urine volume, urea and creatinine levels in urine and serum. Oxidative stress was confirmed by measuring malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels in kidney tissue followed by histopathological studies. RESULTS: CdCl2 administration results in a significant ( p < 0.01) decrease in urine volume, urea, and creatinine levels in urine, as well as GSH, SOD, and CAT levels in renal tissue. In addition, Cd also produced significantly increased ( p < 0.01) urea and creatinine levels in serum and TBARS levels in renal tissues. Rats treated with ROF significantly ( p < 0.01) restore the altered levels of kidney injury markers, nonenzymatic antioxidant, as well as depleted enzymes in dose-dependent manner. An increased expression of NF-κB p65 and decreased expression of GST and NQO1 in the Cd only treated group were significantly reversed by high dose of ROF (1.5 mg/kg). Histopathological changes were also ameliorated by ROF administration in Cd-treated groups. CONCLUSION: In conclusion, ROF treatment showed protective effect against renal damage and increased oxidative stress induced by Cd administration.

Usefulness of urinary parameters in advanced chronic kidney disease. / Utilidad de los parámetros urinarios en la enfermedad renal crónica avanzada.

This review discusses the diagnostic value of urinary parameters in the setting of advanced chronic kidney disease and we present the key concepts that summarise the suggestions of the manuscript. URINARY VOLUME: The amount of fluid intake may be a non-established risk factor for CKD. For these patients, a urinary output ≥2-3 l/day is a reasonable proposal. This recommendation is not applicable to patients with cardiorenal syndrome or fluid overload risk. NA: This determination is very useful to monitor salt intake. Reducing urinary Na<120 mEq/day (≅salt intake≤5-6g) is a reasonable objective. URINARY UREA NITROGEN (UUN): This parameter is useful to estimate protein intake (Maroni BJ equation). A protein intake between 48-72g (0.8-0.9g/kg/day according to weight) is equivalent to UUN 7-10g/day approximately. ACID LOAD AND POTASSIUM: Acid load reduction may be an additional strategy in the nutritional management of this population. It may be estimated indirectly from a diet survey or by measuring the elimination of UUN and Kur. The limits of this recommendation have not been established, but we propose a cautious and prudent diet of fruit and vegetables. PHOSPHORUS: There is a significant positive correlation between phosphorus and protein, both in dietary records and urine elimination. Based on this information, we suggest a urinary P excretion<800mg/day or<600mg/day for patients with GFR<25ml/min or<15ml/min, respectively. CONCLUSION: Urinary parameters provide sensitive and useful knowledge for clinical practice, provide information about the dietary habits of patients and the adherence to our recommendations.

Effect of phyllanthus niruri on metabolic parameters of patients with kidney stone: a perspective for disease prevention

ABSTRACT Phyllanthus niruri (P.niruri) or stone breaker is a plant commonly used to reduce stone risk, however, clinical studies on this issue are lacking. Objective: To prospectively evaluate the effect of P. niruri on the urinary metabolic parameters of patients with urinary lithiasis. Materials and Methods: We studied 56 patients with kidney stones <10mm. Clinical, metabolic, and ultrasonography assessment was conducted before (baseline) the use of P. niruri infusion for 12-weeks (P. niruri) and after a 12-week (wash out) Statistical analysis included ANOVA for repeated measures and Tukey's/McNemar's test for categorical variables. Significance was set at 5%. Results: Mean age was 44±9.2 and BMI was 27.2±4.4kg/m2. Thirty-six patients (64%) were women. There were no significant changes in all periods for anthropometric and several serum measurements, including total blood count, creatinine, uric acid, sodium, potassium, calcium, urine volume and pH; a significant increase in urinary potassium from 50.5±20.4 to 56.2±21.8 mg/24-hour (p=0.017); magnesium/creatinine ratio 58±22.5 to 69.1±28.6mg/gCr24-hour (p=0.013) and potassium/creatinine ratio 39.3±15.1 to 51.3±34.7mg/gCr24-hour (p=0.008) from baseline to wash out. The kidney stones decreased from 3.2±2 to 2.0±2per patient (p<0.001). In hyperoxaluria patients, urinary oxalate reduced from 59.0±11.7 to 28.8±16.0mg/24-hour (p=0.0002), and in hyperuricosuria there was a decrease in urinary uric acid from 0.77±0.22 to 0.54±0.07mg/24-hour (p=0.0057). Conclusions: P.niruri intake is safe and does not cause significant adverse effects on serum metabolic parameters. It increases urinary excretion of magnesium and potassium caused a significant decrease in urinary oxalate and uric acid in patients with hyperoxaluria and hyperuricosuria. The consumption of P.niruri contributed to the elimination of urinary calculi.

Pilot Study Examining the Influence of Potassium Bicarbonate Supplementation on Nitrogen Balance and Whole-Body Ammonia and Urea Turnover Following Short-Term Energy Restriction in Older Men.

With aging there is a chronic low-grade metabolic-acidosis that may exacerbate negative protein balance during weight loss. The objective of this randomized pilot study was to assess the impact of 90 mmol∙day-1 potassium bicarbonate (KHCO3) versus a placebo (PLA) on 24-h urinary net acid excretion (NAE), nitrogen balance (NBAL), and whole-body ammonia and urea turnover following short-term diet-induced weight loss. Sixteen (KHCO3; n = 8, PLA; n = 8) older (64 ± 4 years) overweight (BMI: 28.5 ± 2.1 kg∙day-1) men completed a 35-day controlled feeding study, with a 7-day weight-maintenance phase followed by a 28-day 30% energy-restriction phase. KHCO3 or PLA supplementation began during energy restriction. NAE, NBAL, and whole-body ammonia and urea turnover (15N-glycine) were measured at the end of the weight-maintenance and energy-restriction phases. Following energy restriction, NAE was -9.8 ± 27.8 mmol∙day-1 in KHCO3 and 43.9 ± 27.8 mmol∙day-1 in PLA (p < 0.05). No significant group or time differences were observed in NBAL or ammonia and urea turnover. Ammonia synthesis and breakdown tended (p = 0.09) to be higher in KHCO3 vs. PLA following energy restriction, and NAE was inversely associated (r = -0.522; p < 0.05) with urea synthesis in all subjects. This pilot study suggests some benefit may exist with KHCO3 supplementation following energy restriction as lower NAE indicated higher urea synthesis.

Effect of phyllanthus niruri on metabolic parameters of patients with kidney stone: a perspective for disease prevention.

Phyllanthus niruri (P.niruri) or stone breaker is a plant commonly used to reduce stone risk, however, clinical studies on this issue are lacking. OBJECTIVE: To prospectively evaluate the effect of P. niruri on the urinary metabolic parameters of patients with urinary lithiasis. MATERIALS AND METHODS: We studied 56 patients with kidney stones <10mm. Clinical, metabolic, and ultrasonography assessment was conducted before (baseline) the use of P. niruri infusion for 12-weeks (P. niruri) and after a 12-week (wash out) Statistical analysis included ANOVA for repeated measures and Tukey's/McNemar´s test for categorical variables. Significance was set at 5%. RESULTS: Mean age was 44±9.2 and BMI was 27.2±4.4kg/m2. Thirty-six patients (64%) were women. There were no significant changes in all periods for anthropometric and several serum measurements, including total blood count, creatinine, uric acid, sodium, potassium, calcium, urine volume and pH; a significant increase in urinary potassium from 50.5±20.4 to 56.2±21.8 mg/24-hour (p=0.017); magnesium/creatinine ratio 58±22.5 to 69.1±28.6mg/ gCr24-hour (p=0.013) and potassium/creatinine ratio 39.3±15.1 to 51.3±34.7mg/gCr24- hour (p=0.008) from baseline to wash out. The kidney stones decreased from 3.2±2 to 2.0±2per patient (p<0.001). In hyperoxaluria patients, urinary oxalate reduced from 59.0±11.7 to 28.8±16.0mg/24-hour (p=0.0002), and in hyperuricosuria there was a decrease in urinary uric acid from 0.77±0.22 to 0.54±0.07mg/24-hour (p=0.0057). CONCLUSIONS: P.niruri intake is safe and does not cause significant adverse effects on serum metabolic parameters. It increases urinary excretion of magnesium and potassium caused a significant decrease in urinary oxalate and uric acid in patients with hyperoxaluria and hyperuricosuria. The consumption of P.niruri contributed to the elimination of urinary calculi.

Dietary fibre-rich resistant starches promote ammonia detoxification in the human colon as measured by lactose-[¹5N2]ureide.

Three resistant starches (RSs), namely fibre of potatoes (FP), wrinkle pea starch (WPS), and high amylose maize starch (HAMS) with different dietary fibre contents, were supplemented in adults to evaluate their effects on urinary nitrogen and ammonia excretion as well as on faecal nitrogen excretion by means of lactose-[(15)N2]ureide ((15)N-LU) degradation. Twenty subjects received a regular diet either without or with the supplementation of FP, WPS, and HAMS in a randomized order. After administration of (15)N-LU, urine and faeces were collected over 48 and 72 h, respectively, whereas blood was collected after 6 h. The (15)N-abundances were measured by isotope ratio mass spectrometry. In comparison to the dry run, supplementation with RS significantly lowered renal (15)N-excretion (dry run: 43.2%, FP: 34.6%, WPS: 37.9%, HAMS: 36.4%) as well as the corresponding (15)NH3-excretion (dry run: 0.08%, FP: 0.06%, HAMS: 0.05%), clearly indicating a reduced colonic nitrogen generation at high dietary fibre intake.

Combined Aliskiren and L-arginine treatment reverses renovascular hypertension in an animal model.

Renovascular hypertension is characterized by increased renal sympathetic activity, angiotensin II and by endothelial dysfunction. The purpose of this study was to determine the role of renal sympathetic nerve activity (RSNA) in mediating the anti-hypertensive effects of aliskiren (ALSK) and L-arginine (L-ARG) in a rat renovascular hypertension model. Hypertension was induced by clipping the right renal artery, and the following five groups were divided: SHAM operated; 2-kidney, 1-clip (2K1C); 2K1C plus ALSK; 2K1C plus L-ARG; and 2K1C plus ALSK+ L-ARG. The systolic blood pressure (SBP) of 2K1C rats increased from 114.4±5.2 to 204±12.7 mm Hg (P<0.05) and was only reduced by ALSK+L-ARG treatment (138.4±4.37 mm Hg). The 2K1C hypertension increased the baseline RSNA (SHAM: 62.4±6.39 vs. 2K1C: 97.4±8.43%). L-ARG or ALSK+L-ARG treatment significantly decreased baseline RSNA (2K1C L-ARG:70.7±2.39; 2K1C ALSK+L-ARG: 69.3±4.23%), but ALSK treatment alone did not (2K1C ALSK: 84.2±2.5%). Urinary water, Na(+), Cl(-) and urea excretion were similar in the 2K1C L-ARG, 2K1C ALSK+L-ARG and SHAM groups. The combination of ALSK+L-ARG restored urine flow and increased the glomerular filtration rate. The nNOS expression in the non clipped kidney was significantly increased in 2K1C ALSK+L-ARG rats. In conclusion, combined ALSK+L-ARG treatment normalizes SBP and prevents renal dysfunction in 2K1C hypertensive rats.

Effect of lemongrass tea consumption on estimated glomerular filtration rate and creatinine clearance rate.

OBJECTIVES: The existing research findings regarding the effects of lemongrass (Cymbopogon citratus) tea on renal function indices are conflicting and inconclusive. In the present study, we investigated the effects of infusions prepared from C citratus leaves on creatinine clearance rate (CCr) and estimated glomerular filtration rate (eGFR) in humans. DESIGN AND METHODS: One hundred five subjects (55 men and 50 women) aged 18 to 35 years were randomly assigned to groups set to orally receive infusions prepared from 2, 4, or 8 g of C citratus leaf powder once daily, for 30 days. Serum and urinary levels of urea, creatinine, pH, specific gravity, uric acid, electrolytes, diuretic indices, and eGFR were assessed at days 0, 10, and 30 after the initiation of treatment. Results obtained on days10 and 30 were compared with baseline values. RESULTS: CCr and eGFR decreased significantly at day 30 in both male and female subjects in all the groups and in females treated with infusion prepared from 8 g of C citratus leaf powder for 10 days. At day 10, CCr and eGFR were unchanged in those treated with infusions prepared from 2 or 4 g of the leaf powder, whereas diuretic indices (urine volume, urination frequency, diuretic action, and saliuretic indices) increased above the baseline levels. Serum and urinary creatinine levels significantly increased (P < .05) in both male and female subjects in all the groups. Serum urea significantly increased in the groups treated with infusions prepared from 4 or 8 g of the leaf powder (P < .05) for 30 days. Serum electrolytes remained unchanged, but their urinary levels increased. CONCLUSIONS: We observed dose- and time-dependent adverse effects of C citratus on CCr and eGFR. At a high dose or with prolonged treatment with a low dose, eGFR decrease may be followed by a decline in the other renal function indices.

Nitrate Supplementation, Exercise, and Kidney Function: Are There Detrimental Effects?

PURPOSE: Recently, dietary supplementation with inorganic nitrate (NO3) has been proposed to endurance athletes to increase their performance. However, it has been suggested that an excess of NO3 might be harmful. The present study analyzed the effect of NO3 supplementation on kidney function. METHODS: Thirteen young male subjects performed a 20-min cycling exercise at 85% of the maximal oxygen capacity. Seven days before exercise, the subjects ingested either a placebo (Pl) or 450 mg of potassium nitrate (PN) per day. Venous blood samples and urine collections were collected before and immediately after exercise and after 60 min of recovery. Glomerular filtration rates (GFR) and clearances (Cl) were calculated from serum content and urine output for creatinine (Crn), albumin (Alb), and urea. RESULTS: Under resting conditions, GFR and all clearance measures did not differ between Pl and PN. Immediately after exercise, GFR remained stable in both Pl and PN, whereas Cl-urea decreased significantly (P < 0.05) in Pl (-44%) and PN (-49%). Alb urine outputs were enhanced by 18- to 20-fold in Pl and PN, respectively (P < 0.05). After the recovery period, GFR remained enhanced under Pl conditions, whereas Cl-urea returned to initial values in placebo and nitrate supplementation. Alb output and Cl-Alb remained enhanced under PN conditions. CONCLUSION: These results mainly indicate that dietary nitrate supplementation over a week does not induce any specific kidney function modifications either at rest or during sustained submaximal exercise as compared with Pl.

Effects on milk urea concentration, urine output, and drinking water intake from incremental doses of potassium bicarbonate fed to mid-lactation dairy cows.

Large variation exists in the potassium content of dairy cow feeds and also within a feed type due to soil type and fertilization. Increased ration K concentration causes a subsequent increase in urinary volume and could be expected to also lower milk urea concentration. Six multiparous mid-lactation Swedish Red dairy cows, all fitted with rumen cannulas, were subjected to 3 different levels of K intake in a Latin square experiment with three 2-wk periods to evaluate the effects on concentrations of milk urea and rumen ammonia, urinary output, and drinking water intake. The treatments were achieved by K supplementation on top of a low-K basal ration fed at individual allowances fixed throughout the experiment. The basal ration, consumed at 20.2 kg of dry matter (DM)/d, provided 165 g of crude protein/kg of DM and consisted of grass silage, concentrates, and urea in the proportions 39.3:60.0:0.7 on a DM basis. Potassium bicarbonate supplementation was 0, 616, and 1,142 g/d, respectively, to give total ration K concentrations that were low (LO; 12 g/kg of DM), medium (MED; 23 g/kg of DM), or high (HI; 32 g/kg of DM). Production and composition of milk was not affected by treatment. A linear effect on milk urea concentration was detected, being 4.48, 4.18, and 3.77 mM for LO, MED, and HI, respectively, and a linear tendency for rumen ammonia concentration with 6.65, 6.51, and 5.84 mg of NH3-N/dL for LO, MED, and HI, respectively. Milk urea concentration peaked about 3h after the rumen ammonia peak from the morning feeding, at a level 1.3mM over the baseline. Urinary urea excretion declined linearly (105, 103, and 98 g of urea-N/d for LO, MED, and HI, respectively). Linear increases occurred in urinary output (0.058 ± 0.001 kg of urine/g of K intake; no intercept; coefficient of determination=0.997) and drinking water intake (65.9 ± 2.02 + 0.069 ± 0.004 kg of water/g of K intake; coefficient of determination=0.95). Urinary K concentration leveled off at 12.4 g/L. Urinary creatinine excretion was not affected by K addition, but allantoin excretion increased linearly by 27% from LO to HI, suggesting increased rumen microbial growth. Rumen pH, acetate proportion of total volatile fatty acids, and digestibility of DM, organic matter, and neutral detergent fiber increased linearly with increasing potassium intake. We concluded that increased ration K concentration lowers milk urea concentration with a magnitude significant for the interpretation of milk urea values, but other sources of variation, such as sampling time relative to feeding, may be even more important.

The effects of intravenous, enteral and combined administration of glutamine on malnutrition in sepsis: a randomized clinical trial.

Our aim was to compare the effects of intravenous, enteral, and enteral plus intravenous supplemented glutamine on plasma transferrin, nitrogen balance, and creatinine/height index in septic patients with malnutrition. Blood and urine samples were collected for transferrin, urea and creatinine measurements. Samples, SOFA score and protein-calorie intake values were repeated on days 7 and 15. Patients (n:120) were randomly divided into 4 groups. Group I received 30 g/day IV glutamine, group II received 30 g/day enteral glutamine, group III received 15 g/day IV and 15 g/day enteral glutamine. Group IV received only enteral feeding as a control group. Transferrin levels decreased in group IV (p<0.01 0-7 days, p<0.01 7-15 days, p<0.01 0-15 days). Nitrogen balance levels were highest in group IV when compared with group I (p<0.05, p<0.001), group II (p<0.001), and group III (p<0.05, p<0.001) on days 7-15. Creatinine/height indexes increased in group I (p<0.001), group II (p<0.001), group III (p<0.001), and group IV (p<0.05) on day 15. In group III the creatinine/height index was higher than in groups I and II (p<0.05). In group IV, creatinine/height index was lower than in group I (p<0.01) and group II (p<0.001). Protein-calorie intake in group IV was higher than others on day 7 (p<0.05). SOFA scores of group IV were higher than the other groups on day 15 (p<0.05). This study demonstrated, that combined route of gln supplementation resulted in the most positive outcome to transferrin, creatine/height index and nitrogen balance (on days 7 and 15) during the catabolic phase of septic patients with malnutrition.

Aqueous extract of Allium sativum L bulbs offer nephroprotection by attenuating vascular endothelial growth factor and extracellular signal-regulated kinase-1 expression in diabetic rats.

To investigate the nephroprotective effect of garlic and elucidate the mechanism by which it prevents the progression of diabetic nephropathy in diabetic rats, diabetes was induced by a single ip injection of streptozotocin (45 mg/kg body weight). Garlic extract (500 mg/kg body weight) and aminoguanidine (1 g/L) were supplemented in the treatment groups. Histopathological examination using H&E, PAS staining and the immunohistochemical analysis of vascular endothelial growth factor (VEGF) and extracellular signal-regulated kinase-1 (ERK-1) expression were performed on kidney sections at the end of 12 weeks. Significant change in both, the urine and serum biochemistry confirmed kidney damage in diabetic animals which was further confirmed by the histological changes such as mesangial expansion, glomerular basement membrane thickening, glycosuria and proteinuria. However, the diabetic animals treated with garlic extract showed a significant change in urine and serum biochemical parameters such as albumin, urea nitrogen and creatinine compared to that of diabetic rats. Further, the garlic supplemented diabetic rats showed a significant decrease in the expression of VEGF and ERK-1 compared to diabetic rats, attenuating mesangial expansion and glomerulosclerosis. Thus, garlic extract rendered nephroprotection in diabetic rats.

Effects of raftilose on serum biochemistry and liver morphology in rats fed with normal or high-fat diet.

Non-alcoholic fatty liver disease is the leading cause of chronic liver injury in developed countries. Oligofructose (OFS) is a prebiotic with proven benefits for health. The aim of the study is to evaluate the effect of 10% OFS on hepatic morphology and lipid metabolism in Wistar Kyoto rats submitted to normal diet (ND) or high-fat diet (FD). Animals were treated for 7 weeks. Lipid profile and serum alkaline phosphatase (ALP) activity were measured and liver histology evaluated at the end of the study. Ten percent OFS reduced triglyceride (TAG) levels when added to any of the diet regimens; 10% OFS decreased plasmatic urea in ND and plasmatic and urinary urea levels in FD; ND + 10% OFS treated rats showed lower ALP activity than controls. FD increased ALP activity, an effect not reversed by OFS. Animals submitted to FD have microscopic hepatic changes: marked steatosis with disarranged centrilobular zone structure; enlarged sinusoids; enlarged mitochondria and an increase in number and volume of adiposomes. Supplementation with 10% OFS in FD reversed those effects. In conclusion, 10% OFS supplementation prevented deleterious effects of FD such as alterations on lipid profile (TAG elevation) and hepatic morphologic changes. OFS decreased ALP activity in animals subjected to ND, which may have contributed to the differences on lipid metabolism.

Severe hypernatremia from a urea-induced diuresis due to body protein wasting in an insulin-resistant type 2 diabetic patient.

CONTEXT: Hypernatremia is encountered after pituitary or hypothalamic surgery and typically is secondary to vasopressin deficiency resulting in increased free water clearance with inadequate water replacement. OBJECTIVE: We report a type 2 diabetic patient with severe hypernatremia (Na⁺ = 161 mEq/L) after hypothalamic surgery. Unexpectedly, this was accompanied by persistent urinary hypertonicity and negative total but positive electrolyte free water clearance. MAIN OUTCOME MEASURE: Measurement of urinary electrolytes and urea revealed that an osmotic diuresis induced by urea derived principally by breakdown of endogenous protein was causative. Body protein losses over 48 hours were estimated to exceed 2 kg of lean mass. High-dose glucocorticoid, insulin resistance, and a postsurgical catabolic stress likely contributed. CONCLUSION: In surgically severely stressed individuals, proteolysis of endogenous protein can strongly impact body water metabolism and contribute to severe hypernatremia.