Urea Excretion Research Articles

Reproductive colonization of land by frogs: Embryos and larvae excrete urea to avoid ammonia toxicity.

Vertebrate colonization of land has occurred multiple times, including over 50 origins of terrestrial eggs in frogs. Some environmental factors and phenotypic responses that facilitated these transitions are known, but responses to water constraints and risk of ammonia toxicity during early development are poorly understood. We tested if ammonia accumulation and dehydration risk induce a shift from ammonia to urea excretion during early stages of four anurans, from three origins of terrestrial development. We quantified ammonia and urea concentrations during early development on land, under well‐hydrated and dry conditions. Where we found urea excretion, we tested for a plastic increase under dry conditions and with ammonia accumulation in developmental environments. We assessed the potential adaptive role of urea excretion by comparing ammonia tolerance measured in 96h‐LC50 tests with ammonia levels in developmental environments. Ammonia accumulated in foam nests and perivitelline fluid, increasing over development and reaching higher concentrations under dry conditions. All four species showed high ammonia tolerance, compared to fishes and aquatic‐breeding frogs. Both nest‐dwelling larvae of Leptodactylus fragilis and late embryos of Hyalinobatrachium fleischmanni excreted urea, showing a plastic increase under dry conditions. These two species can develop the longest on land and urea excretion appears adaptive, preventing their exposure to potentially lethal levels of ammonia. Neither late embryos of Agalychnis callidryas nor nest‐dwelling larvae of Engystomops pustulosus experienced toxic ammonia levels under dry conditions, and neither excreted urea. Our results suggest that an early onset of urea excretion, its increase under dry conditions, and elevated ammonia tolerance can all help prevent ammonia toxicity during terrestrial development. High ammonia represents a general risk for development which may be exacerbated as climate change increases dehydration risk for terrestrial‐breeding frogs. It may also be a cue that elicits adaptive physiological responses during early development.

Assessment of Proximal Tubular Function by Tubular Maximum Phosphate Reabsorption Capacity in Heart Failure.

The estimated glomerular filtration rate (eGFR) is a crucial parameter in heart failure. Much less is known about the importance of tubular function. We addressed the effect of tubular maximum phosphate reabsorption capacity (TmP/GFR), a parameter of proximal tubular function, in patients with heart failure. We established TmP/GFR (Bijvoet formula) in 2085 patients with heart failure and studied its association with deterioration of kidney function (>25% eGFR decrease from baseline) and plasma neutrophil gelatinase-associated lipocalin (NGAL) doubling (baseline to 9 months) using logistic regression analysis and clinical outcomes using Cox proportional hazards regression. Additionally, we evaluated the effect of sodium-glucose transport protein 2 (SGLT2) inhibition by empagliflozin on tubular maximum phosphate reabsorption capacity in 78 patients with acute heart failure using analysis of covariance. Low TmP/GFR (<0.80 mmol/L) was observed in 1392 (67%) and 21 (27%) patients. Patients with lower TmP/GFR had more advanced heart failure, lower eGFR, and higher levels of tubular damage markers. The main determinant of lower TmP/GFR was higher fractional excretion of urea (P<0.001). Lower TmP/GFR was independently associated with higher risk of plasma NGAL doubling (odds ratio, 2.20; 95% confidence interval, 1.05 to 4.66; P=0.04) but not with deterioration of kidney function. Lower TmP/GFR was associated with higher risk of all-cause mortality (hazard ratio, 2.80; 95% confidence interval, 1.37 to 5.73; P=0.005), heart failure hospitalization (hazard ratio, 2.29; 95% confidence interval, 1.08 to 4.88; P=0.03), and their combination (hazard ratio, 1.89; 95% confidence interval, 1.07 to 3.36; P=0.03) after multivariable adjustment. Empagliflozin significantly increased TmP/GFR compared with placebo after 1 day (P=0.004) but not after adjustment for eGFR change. TmP/GFR, a measure of proximal tubular function, is frequently reduced in heart failure, especially in patients with more advanced heart failure. Lower TmP/GFR is furthermore associated with future risk of plasma NGAL doubling and worse clinical outcomes, independent of glomerular function.

POS-262 LOW-PROTEIN DIETS IN CHRONIC KIDNEY DISEASE – SAFE OR NOT? A SINGLE LARGE CENTER EXPERIENCE

Recent studies emphasized the role of low-protein diets (LPDs) in the management of chronic kidney disease (CKD) in order to postpone renal replacement therapy. However, the risk of malnutrition in CKD patients on LPDs has often been debated. We present the results of a large single-center, focusing on the safety of LPDs in both diabetic and non-diabetic patients with CKD. A prospective, randomized, controlled study with 207 non-diabetic patients with CKD stage 4+ were grouped by the type of nutritional intervention - vegetarian very low protein diet with 0.3g/kg-day supplemented with ketoanalogues of essential aminoacids (sVLPD) versus LPD with 0.6g/kg-day for 15 months. We present the safety parameters at the end of study (EOS), but also after 10 years of follow-up. Safety data from a second interventional study, including 97 diabetic patients with stage 4+ CKD who received LPD supplemented with ketoanalogues of essential aminoacids (sLPD) for 12 months are also presented. Subjective Global Assessment (SGA), clinical data (Body Mass Index, BMI), and biochemical parameters (serum albumin, C-reactive protein) were analyzed. Patients’ adherence to the type of nutritional intervention was assessed by the estimated protein intake using urinary urea excretion. Both protein and energy intake were also evaluated through food diary. Nutritional status of non-diabetic patients was preserved for both sVLPD and LPD at 15 months after inclusion (SGA A 84 versus 85%, p=0.83). Moreover, the subjects continued the nutritional intervention after the EOS. After 10 years of nutritional intervention, the kidney’s survival (86 versus 46%, p<0.0001) and patients’ survival (89 versus 60%, p<0.0001) were much better in the sVLPD group. The levels of serum albumin were constantly around 4 g/dL, without any significant differences between groups at all study moments. The C-reactive protein levels were lower in patients on sVLPD at 15 months after inclusion (4 versus 5 mg/L, p<0.0001), respectively at 10 years after inclusion (5 versus 10 mg/L, p<0.0001). Patients’ adherence was confirmed at all study moments. For diabetic patients, during the study, there were improvements in body weight (BMI 27.1 versus 26.0 kg/m², p<0.0001), serum albumin (3.9 to 4.1 g/dL, p<0.0001), and in C-reactive protein levels (14 to 9 mg/L, p<0.0001). All patients had SGA A throughout the study. Nutritional intervention with different low-protein regimens seem to be safe for patients with CKD, both in diabetics and in non-diabetics.

Kidney functions adaptations of professional soccer players in response to an entire game season.

This study investigated the renal function of soccer players after an entire game-season. Thirty-five athletes recruited to play for the Macae Futebol Clube were invited for this study, of which 18 athletes completed the entire game season. Blood and 24-hour urine were collected at the beginning (Pre-Season) and the end of the game season (Post-Season). Kidney functions were assessed by calculating the urinary excretion, clearance, and fractional excretion of the selected solutes. Plasma creatinine, sodium, total protein, and osmolality were lower in the Post-Season . In contrast, plasma urea was higher in the Post-Season period. Urinary excretion of urea was reduced while albumin excretion was higher in comparison to Pre-Season. The clearances of creatinine, total proteins, and albumin were higher in the Post-Season period. In accordance, the fractional excretion of albumin increased. On the other hand, the clearance and fractional excretion of urea was lower in the Post-Season period. These results show that soccer-associated exercise throughout the entire game-season induces kidney functions adaptations that may prevent dehydration in these athletes through increased urea reabsorption to conserve water. In addition, this data corroborates to increased glomerular permeability to plasma proteins, such as albumin, that soccer players may experience.

Utility of Fractional Excretion of Urea in Diagnosing Etiology of AKI in Cirrhosis

Background: Acute kidney injury is present in a third of hospitalized patients with cirrhosis. AKI in cirrhosis can be functional (Pre renal azotemia and Hepatorenal syndrome) or structural (Acute tubular necrosis). Distinguishing the precise etiology of AKI in cirrhosis remains a clinical challenge. Fractional excretion of sodium as a marker of functional AKI has several limitations.

Utility of Fractional Excretion of Urea (FeUrea) for differentiating AKI phenotypes in patients with cirrhosis and ascites.

Background and Aim: Acute renal failure (AKI) is a common complication of decompensated cirrhosis and confers a poor prognosis. AKI in these patients may result from functional decrease in renal function as in prerenal azotaemia (PRA) and Hepato-renal syndrome (HRS) or due to structural renal abnormalities as in acute tubular necrosis (ATN). These phenotypes of AKI have therapeutic and prognostic implications. However, in clinical practice, approaches to determine the cause of AKI in these patients are suboptimal.

Effect of timing of paddock allocation in tropical grass on performance, nitrogen excretion, and enteric methane emissions from dairy cows.

The objective of this study was to investigate the influence of timing of paddock allocation (AM or PM) in tropical grass on nutritive value of the herbage, dry matter intake (DMI), milk yield and composition, ruminal fermentation, nitrogen excretion, and enteric CH4 emissions of dairy cows. Twenty cows were grouped in pairs and randomly distributed within pair to one of two treatments. PM herbage had greater contents of dry matter (DM), soluble carbohydrates, starch, and nonfibrous carbohydrate to protein ratio and lower contents of neutral detergent fiber and acid detergent fiber. There was no treatment effect on DMI, N excretion, milk yield, and CH4 emissions. However, milk protein and casein yields tended to be greater for PM than AM, while milk urea nitrogen concentration was lower for PM than AM. The increase in nutritive value of the afternoon relative to the morning herbage within the framework of this study was not large enough to increase DMI and milk yield or to decrease CH4 emission intensity by the dairy cows as hypothesized. The findings indicate that PM treatment can be a simple and useful grazing strategy that results in an herbage harvest with greater nutritional value and in lower excretion of urea N into milk.

Amino Acid- Essentiality to Human Body

An amino acid is one of the major building block of protein unit, arranged around the carbon atom in tetrahedral manner. These are classified into essential and non-essential amino acids based on their availability on the body. As many as 300 amino acids, only 20 are standard amino acid for their functional view. Each amino acid i.e. monomers joined with peptide linkage as a result biggest molecule of amino acid forms where larger molecule represented by R-group/s. Rich sources of it are pulses, seeds, non-veg foods as well as animal products. Amino acids play major role in metabolic activities for human beings and supply the energy to the body and get healthy fitness as well as neurotans mitters. Excretion of urea and CO2 also results due to the different reaction occurring in liver and kidney. Metabolic disorder causes phenylketonuria, alkaptonuria, albinism like problems. Detection of amino acids can be done by various measures but mostly utilized method is ninhydr in test, is a chemical process where the development of coloration confirms the presence of amino acid.

Urea Excretion and Arginase Activity as New Biomarkers for Nitrite Stress in Freshwater Aquatic Animals

Background: In recent years, the concern has been growing on increasing aquatic nitrite levels due to anthropogenic activities. Crustaceans and fish easily uptake nitrite via the chloride uptake system of gills. High nitrite body levels may interfere with nitric oxide (NO) production by nitric oxide synthase (NOS). The arginase, which catalyzes arginine conversion to ornithine and urea, is central to NO homeostasis. In vivo, changes in the arginase activity alter urea body levels and urea excretion and modulate NOS by altering arginine availability for NO synthesis. Excess arginase activity may uncouple NOS and induce oxidative stress. Methods: We tested muscle arginase activity and urea excretion in two fish species, zebrafish and convict cichlid, and the crustacean Yamato shrimp, under sub-lethal nitrite stress. Results: Exposure to nitrite (2 mM in the fish, 1 mM in the shrimp) significantly increased blood nitrite concentration in all species. Concomitantly, nitrite stress significantly increased arginase activity, urea excretion, and urea levels in the blood. In Yamato shrimp, urea levels also increased in muscle. Conclusion: Our results agree with the hypothesis that nitrite stress affects NO homeostasis by arginase stimulation and urea excretion. These parameters might function as markers of sub-lethal nitrite stress in freshwater fish and crustaceans.

Effects of a protein-restricted diet on body weight and serum tyrosine concentrations in patients with alkaptonuria.

In an open‐label, controlled study of nitisinone in alkaptonuria (SONIA 2), patients were advised to lower dietary protein intake to reduce serum tyrosine (s‐Tyr) levels and the risk of keratopathy. A body weight increase was observed in the nitisinone‐treated patients but not in the control group. To investigate the effectiveness and consequence of protein restriction in patients with alkaptonuria, a post‐hoc analysis of SONIA 2 was performed. One hundred and thirty‐eight patients were randomised (nitisinone: n = 69, controls: n = 69). Comparison of baseline and Month 12 data on 24‐h urinary excretion of HGA (u‐HGA24) and urea (u‐urea24, used as an approximate protein intake measure), tyrosine and body weight were performed using paired t tests. Comparisons of data between groups were made using 2‐sample t tests. We found that u‐urea24 decreased more in nitisinone‐treated than controls. The study centre with lowest average s‐Tyr and u‐urea24 (nitisinone arm) at Month 12 also had lowest keratopathy incidence (3.1%), while the centre with highest values showed the highest (14.6%). S‐Tyr was generally high in those with keratopathy, but those without keratopathy had similar elevated values. A similar pattern across centres was seen for body weight changes, with a statistically significant weight increase in nitisinone‐treated patients at centres with lower u‐urea24 values. Therefore, in nitisinone‐treated patients, protein restriction led to increased body weight but may also have lowered the risk of developing keratopathies. If introduced, a protein‐restricted diet should be supervised by a dietician and, when appropriate, include amino acid supplements deficient in tyrosine and phenylalanine, to avoid malnutrition and undesired weight increase.

The ratio of measured to estimated glomerular filtration rate may be a marker of early mortality and dialysis requirement

BackgroundIt has been suggested that, in patients with CKD stage 5, measured GFR (mGFR), defined as the mean of urea and creatinine clearance, as measured by a 24-h urine collection, is a better measure of renal function than estimated GFR (eGFR), based on the CKD-EPI formula. This could be due to reduced muscle mass in this group. Its use is recommended in the ERBP guidelines. Unplanned dialysis initiation (DI) is associated with increased morbidity, mortality, and reduced modality choice and is generally considered undesirable. We hypothesized that the ratio mGFR/eGFR (M/E) aids prediction of death and DI.MethodsAll 24-h measurements of urea and creatinine excretion were extracted from the clinical biochemistry databases in Zealand. Data concerning renal diagnosis, comorbidity, biochemistry, medical treatment, mortality and date of DI, were extracted from patient notes, the National Patient Registry and the Danish Nephrology Registry. Patients were included if their eGFR was < 30 ml/min/1.73m2. The last available value for each patient was included. Follow-up was 12 months.ResultsOne thousand two hundred sixty-five patients were included. M/E was median 0.91 ± 0.43. It was highly correlated to previous determinations. It was negatively correlated to eGFR, comorbidity, high age and female sex. It was positively related to albumin and negatively to C-reactive protein. M/E was higher in patients treated with ACE inhibitors and diuretics but no other treatment groups.On a multivariate analysis, M/E was negatively correlated with mortality and combined mortality/DI, but not DI. A post hoc analysis showed a negative correlation to DI at 3 months. For patients with an eGFR 10–15 ml/min/1.73m2, combined mortality and DI at 3 months was for low M/E (< 0.75) 36%, medium (0.75–1.25) 20%, high (> 1.25) 8%. A low M/E predicted increased need for unplanned DI.A supplementary analysis in 519 patients where body surface area values were available, allowing BSA-corrected M/E to be analyzed, revealed similar results.ConclusionA low mGFR/eGFR ratio is associated with comorbidity, malnutrition, and inflammation. It is a marker of early DI, mortality, and unplanned dialysis initiation, independently of eGFR, age and comorbidity. Particular attention paid to patients with a low M/E may lower the incidence of unplanned dialysis requirement.

High-Normal Protein Intake Is Not Associated With Faster Renal Function Deterioration in Patients With Type 2 Diabetes: A Prospective Analysis in the DIALECT Cohort.

To study the prospective association between dietary protein intake and renal function deterioration in patients with type 2 diabetes (T2D). Prospective analyses were performed in data of 382 patients of the Diabetes and Lifestyle Cohort Twente (DIALECT) study. Dietary protein intake was determined by the Maroni equation from 24-h urinary urea excretion. Renal function deterioration was defined as need for renal replacement therapy or a persistent increase of ≥50% in serum creatinine. Cox proportional hazards models were used to calculate hazard ratios (HRs) for the association between dietary protein intake and renal function deterioration. Threshold levels represent the dietary protein intake at which there was a significantly increased and reduced hazard of renal function deterioration. Renal function deterioration occurred in 53 patients (14%), with a median follow-up duration of 6 (interquartile range 5-9) years. Mean dietary protein intake was 91 ± 27 g/day (1.22 ± 0.33 g/kg ideal body weight/day). Dietary protein intake was inversely associated with renal function deterioration (HR 0.62 [95% CI 0.44-0.90]). Patients with an intake <92 g/day had an increased hazard for renal function deterioration (HR 1.44 [95% CI 1.00-2.06]), while patients with an intake >163 g/day had a decreased hazard for renal function deterioration (HR 0.42 [95% CI 0.18-1.00]). Regarding dietary protein intake per kilogram body weight, patients with an intake <1.08 g/kg/day had an increased hazard for renal function deterioration (HR 1.63 [95% CI 1.00-2.65]). In patients with T2D, unrestricted dietary protein intake was not associated with an increased hazard of renal function deterioration. Therefore, substituting carbohydrates with dietary protein is not contraindicated as a part of T2D management, although it may have a positive effect on body weight while minimizing loss of muscle mass.

Comparison of nutrient costs from fish feeds and inorganic fertilizers for aquaponics systems

One potential advantage of aquaponic systems is reduced resource consumption compared to separate fish and plant rearing systems, but little has been published on the costs of providing nitrogen and phosphorus nutrients by fish in comparison to the purchase of inorganic fertilizers. The cost of providing nitrogen and phosphorus from six commercial fish feeds was compared to 9 commercial agricultural fertilizers. Waste production from fish was corrected for excretion of urea and the impact of feed wastage. For a typical aquaponic system without mineralization of fecal solids, the soluble nitrogen and phosphorus excretion ranged from 36.9 to 44.0 g/kg feed and 1.4–3.7 g/kg feed, respectively. The cost to provide 1 kg of nutrients from feeds ranged from $15-$29/kg for nitrogen and from $115 - $583/kg for phosphorus. Compared to the purchase of these elements from inorganic fertilizers, the feeds were 7–14 times more expensive for nitrogen and 17–88 times more expensive for phosphorus. The feed/fertilizer cost ratio (FFCRfeed) required to replace the nitrogen and phosphorus in 1 kg of feed ranged from 2 to 4 times for monoammonium phosphate to 14–17 times for anhydrous ammonia and triple superphosphate. Based on the specific conditions and assumptions in this work, the economic value of nutrients provided by fish in aquaponic systems has been greatly over-stated.

Postprandial renal haemodynamic effects of the dipeptidyl peptidase‐4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): A predefined substudy of a randomized, double‐blind trial

AimTo determine the effect of the dipeptidyl peptidase‐4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D).Materials and MethodsIn this predefined substudy within a randomized, double‐blind, parallel‐group, intervention trial, overweight people with T2D without renal impairment were treated with once‐daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add‐on to metformin for 8 weeks. After a standardized liquid protein‐rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para‐aminohippuric acid clearance, respectively, based on timed urine sampling. Intrarenal haemodynamics were estimated using the Gomez equations. Glucoregulatory/vasoactive hormones, urinary pH and fractional excretions (FE) of sodium, potassium and urea were measured.ResultsCompared with glimepiride, linagliptin increased the postprandial filtration fraction (FF; mean difference 2.1%‐point; P = .016) and estimated glomerular hydraulic pressure (mean difference 3.0 mmHg; P = .050), and tended to increase GFR (P = .08) and estimated efferent renal arteriolar resistance (RE; P = .08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference −0.40%; P = .004), without between‐group differences in time‐averaged postprandial glucose levels. In the linagliptin group, change in FF correlated with change in mean arterial pressure (R = 0.807; P = .009) and time‐averaged mean glucagon (R = 0.782; P = .008), but not with changes in glucose, insulin, intact glucagon‐like peptide‐1, renin or FENa. Change in glucagon was associated with change in RE (R = 0.830; P = .003).ConclusionsIn contrast to our hypothesis, compared with glimepiride, linagliptin does not reduce postprandial hyperfiltration, yet appears to increase FF after meal ingestion by increasing blood pressure or RE.

The Significance of “Fractional Excretion of Urea” in The Differential Diagnosis of Acute Kidney Injury in Cirrhotic Patients

Abstract Background Patients with cirrhosis are more susceptible to develop AKI than the non-cirrhotic individuals. AKI has an estimated prevalence of approximately 20% to 50% among hospitalized patients with cirrhosis. Physicians caring for patients with cirrhosis should recognize the acute or chronic character of renal disease, the causes of renal injury, the clinical conditions leading concomitantly to AKI and liver dysfunction, and the prognostic factors associated with the progression of AKI. Hypovolemia (due to diuretics, hemorrhage and diarrhea), acute tubular necrosis (ATN), sepsis, nephrotoxic agents (such as nonsteroidal anti-inflammatory drugs, aminoglycosides and/or radiological contrasts) and hepatorenal syndrome (HRS)-type 1 are the most common causes of AKI in cirrhotic patients. Objective To evaluate the sensitivity of fractional excretion of urea (FEUrea) vas a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis. Patients and Methods This study was conducted in co-operation between Tropical Medicine Department, Ain-Shams University and the Gastroenterology and Hepatology Department, Theodor Bilharz Research Institute between July 2019 to January 2020. It included 70 adult Egyptian patients admitted for treatment of complications of cirrhosis who fulfilled the eligibility criteria and compared to 10 cirrhotic patients without renal impairment. All patients were subjected to; full history taking, thorough clinical examination, laboratory investigations, Child-Pugh score was calculated for admission and urine samples were collected for urinary urea and creatinine levels to calculate FEUrea. Results Concerning the gender distribution in this study, male to female percent was 40 (57.10%) males and 30 (42.90%) females for gender, respectively. As regards to the causes of AKI, there were 24 (34.30%) PRA, 7 (10.00%) HRS and 39 (55.70%) ATN for final diagnosis. In the current study, there was significant difference (P = 0.0001; P &amp;lt; 0.05) in FE urea % among PRA, HRS and ATN groups (26.28±2.89, 11.76±3.44, and 47.37±10.53, respectively). Findings showed a higher FEUrea cut-off for ATN (&amp;gt;33%) compared to lower cut-off values for PRA (&amp;lt;33% and &amp;gt;21%) and HRS (&amp;lt;21%). Conclusion FEUrea was found to be an excellent simple tool for the differential diagnosis of AKI in patients with decompensated cirrhosis and ascites. FEUrea has also proven to be a useful “tubular injury” marker by differentiating ATN from non-ATN with high diagnostic accuracy (Sensitivity and Specificity exceeding &amp;gt;90%). FEUrea was found to be a good alternative and noninvasive tool for differentiating causes of AKI in cirrhotic patients instead of other non-available or expensive markers.

Antihypertensive and metabolic effects of empagliflozin in Ren-2 transgenic rats, an experimental non-diabetic model of hypertension

The new antidiabetic drugs, gliflozins, inhibit sodium-glucose transporter-2 in renal proximal tubules promoting glucose and sodium excretion. This leads not only to a significant improvement of glucose control but also to the reduction of blood pressure and body weight in both diabetic patients and experimental models. We examined whether these beneficial effects can also be achieved in a non-diabetic hypertensive model, namely in Ren-2 transgenic rats (TGR). Adult 6-month-old hypertensive TGR and their normotensive controls (Hannover Sprague-Dawley rats), were either untreated or treated with empagliflozin (10 mg/kg/day) for two months. Telemetric blood pressure monitoring, renal parameters as well as cardiac function via echocardiography were analyzed during the experiment. At the end of the study, the contribution of major vasoactive systems to blood pressure maintenance was studied. Metabolic parameters and markers of oxidative stress and inflammation were also analyzed. Empagliflozin had no effect on plasma glucose level but partially reduced blood pressure in TGR. Although food consumption was substantially higher in empagliflozin-treated TGR compared to the untreated animals, their body weight and the amount of epididymal and perirenal fat was decreased. Empagliflozin had no effect on proteinuria, but it decreased plasma urea, attenuated renal oxidative stress and temporarily increased urinary urea excretion. Several metabolic (hepatic triglycerides, non-esterified fatty acids, insulin) and inflammatory (TNF-α, leptin) parameters were also improved by empagliflozin treatment. By contrast, echocardiography did not reveal any effect of empagliflozin on cardiac function. In conclusion, empagliflozin exerted beneficial antihypertensive, anti-inflammatory and metabolic effects also in a non-diabetic hypertensive model.

Fractional Excretion of Sodium and Urea in Differentiating Acute Kidney Injury Phenotypes in Decompensated Cirrhosis

Prerenal acute kidney injury (prerenal AKI), hepatorenal syndrome (HRS-AKI), and acute tubular necrosis (ATN-AKI) are the various phenotypes of acute kidney injury, which are described in decompensated cirrhosis. It has therapeutic and prognostic implications. We aimed to evaluate the diagnostic utility of fractional excretion of sodium and urea (FENa and FEUrea) for differentiating AKI phenotypes. A prospective analysis was performed in 200 patients with decompensated cirrhosis with AKI to derive receiver operating curve, optimal cut-off, sensitivity, and specificity. These findings were validated in an independent cohort (n=50) to differentiate ATN-AKI, HRS-AKI, and prerenal AKI. The incidence of prerenal AKI, HRS-AKI, and ATN-AKI were 37.5%, 34%, and 28.5% in the derivation cohort and 28%, 38%, and 34% in the validation cohort respectively. The median FENa was significantly different in various phenotypes of AKI in the derivation and validation cohort (P 0.001); FEUrea was significantly different in the derivation cohort (P 0.0001), not in the validation cohort (P 0.106). The AUC for FENa (cut-off, sensitivity/specificity) was 86.6% (0.567, 89/71) and for FEUrea was 60.3% (34.73, 70/58) for ATN-AKI vs. non-ATN-AKI. The area under the curve for FENa to differentiate between HRS-AKI vs. non-HRS-AKI was 74.5%. FEUrea could not differentiate HRS-AKI vs. non-HRS-AKI (AUC 60.4%) satisfactorily. FENa and FEUrea were unable to differentiate between prerenal AKI and HRS-AKI (AUC <70%). Among cirrhotics FENa at admission is a simple, commonly available clinical tool that can be used to differentiate structural AKI from prerenal AKI and HRS-AKI. The newly derived lowered cut-off value of FENa makes the diagnosis of ATN-AKI easier, faster and thus obviates the need for extensive workup in a significant proportion of patients. FENa appears better than FEUrea in decompensated cirrhosis with AKI.

High mean arterial pressure target to improve sepsis-associated acute kidney injury in patients with prior hypertension: a feasibility study

BackgroundThe optimal mean arterial pressure (MAP) in cases of septic shock is still a matter of debate in patients with prior hypertension. An MAP between 75 and 85 mmHg can improve glomerular filtration rate (GFR) but its effect on tubular function is unknown. We assessed the effects of high MAP level on glomerular and tubular renal function in two intensive care units of a teaching hospital. Inclusion criteria were patients with a history of chronic hypertension and developing AKI in the first 24 h of septic shock. Data were collected during two 6 h periods of MAP regimen administered consecutively after haemodynamic stabilisation in an order depending on the patient's admission unit: a high-target period (80–85 mmHg) and a low-target period (65–70 mmHg). The primary endpoint was the creatinine clearance (CrCl) calculated from urine and serum samples at the end of each MAP period by the UV/P formula.Results26 patients were included. Higher urine output (+0.2 (95%:0, 0.4) mL/kg/h; P = 0.04), urine sodium (+6 (95% CI 0.2, 13) mmol/L; P = 0.04) and lower serum creatinine (− 10 (95% CI − 17, − 3) µmol/L; P = 0.03) were observed during the high-MAP period as compared to the low-MAP period, resulting in a higher CrCl (+25 (95% CI 11, 39) mL/mn; P = 0.002). The urine creatinine, urine–plasma creatinine ratio, urine osmolality, fractional excretion of sodium and urea showed no significant variation. The KDIGO stage at inclusion only interacted with serum creatinine variation and low level of sodium excretion at inclusion did not interact with these results.ConclusionsIn the early stage of sepsis-associated AKI, a high-MAP target in patients with a history of hypertension was associated with a higher CrCl, but did not affect the kidneys' ability to concentrate urine, which may reflect no effect on tubular function.

Effects of dietary inclusion with rapeseed cake containing high glucosinolates on nitrogen metabolism and urine nitrous oxide emissions in steers.

Two consecutive trials were conducted to investigate the effects of glucosinolates (GLS) in rapeseed cake (RSC) on nitrogen (N) metabolism and urine nitrous oxide (N2O) emissions in steers. In trial 1, 8 steers and 4 levels of RSC, i.e. 0, 2.7%, 5.4% and 8.0% dry matter (DM) (0, 6.0, 12.1, 18.1 μmol GLS/g DM) were allocated in a replicated 4 × 4 Latin square. In trial 2, the static incubation technique was used for measuring the N2O emissions of the urine samples collected from trial 1. The results of trial 1 indicated that dietary inclusion of RSC decreased the digested N and increased the fecal N excretion (P < 0.01), whereas it did not affect the urinary N excretion, total N excretion and N retention (P > 0.10). Dietary inclusion of RSC decreased the urinary excretion of urea while it increased allantoin, total purine derivatives, the predicted rumen microbial N flow and thiocyanate (SCN) (P < 0.05). Dietary inclusion of RSC did not affect the plasma triiodothyronine and thyroxine while it down-regulated the plasma relative concentrations of 4-aminohippuric acid, 3α,7α-dihydroxycoprostanic acid, phosphatidylserine (14:0/16:0), 6β-hydroxyprogesterone, pyrrhoxanthinol, tatridin B, mandelonitrile rutinoside, taraxacoside (P < 0.05), and up-regulated hypoglycin B, neuromedin N (1-4), dhurrin, 5-deoxykievitone (P < 0.01). The results of trial 2 indicated that dietary RSC increased the steer urine N2O–N fluxes, the ratio of N2O–N to N application and the estimated steer urine N2O–N emissions (P < 0.01). A close correlation was found between the estimated steer urine N2O–N emissions and the output of urinary SCN (P < 0.001). In conclusion, dietary RSC increased the fecal N excretion, whereas it did not affect the urinary N excretion and the N retention rate in steers. Dietary RSC increased rather than decreased the urine N2O–N emissions even though it decreased the urinary excretion of urea. The SCN excreted in urine could be the major factor in increasing the urine N2O–N emissions. Whether other metabolites excreted into urine from RSC have an impact on the urine N2O–N emissions in steers needs to be investigated in the future.

Acute Decompensated Heart Failure and the Kidney: Physiological, Histological and Transcriptomic Responses to Development and Recovery.

BACKGROUNDAcute decompensated heart failure (ADHF) is associated with deterioration in renal function—an important risk factor for poor outcomes. Whether ADHF results in permanent kidney damage/dysfunction is unknown.METHODS AND RESULTSWe investigated for the first time the renal responses to the development of, and recovery from, ADHF using an ovine model. ADHF development induced pronounced hemodynamic changes, neurohormonal activation, and decline in renal function, including decreased urine, sodium and urea excretion, and creatinine clearance. Following ADHF recovery (25 days), creatinine clearance reductions persisted. Kidney biopsies taken during ADHF and following recovery showed widespread mesangial cell prominence, early mild acute tubular injury, and medullary/interstitial fibrosis. Renal transcriptomes identified altered expression of 270 genes following ADHF development and 631 genes following recovery. A total of 47 genes remained altered post‐recovery. Pathway analysis suggested gene expression changes, driven by a network of inflammatory cytokines centered on IL‐1β (interleukin 1β), lead to repression of reno‐protective eNOS (endothelial nitric oxide synthase) signaling during ADHF development, and following recovery, activation of glomerulosclerosis and reno‐protective pathways and repression of proinflammatory/fibrotic pathways. A total of 31 dysregulated genes encoding proteins detectable in urine, serum, and plasma identified potential candidate markers for kidney repair (including CNGA3 [cyclic nucleotide gated channel subunit alpha 3] and OIT3 [oncoprotein induced transcript 3]) or long‐term renal impairment in ADHF (including ACTG2 [actin gamma 2, smooth muscle] and ANGPTL4 [angiopoietin like 4]).CONCLUSIONSIn an ovine model, we provide the first direct evidence that an episode of ADHF leads to an immediate decline in kidney function that failed to fully resolve after ≈4 weeks and is associated with persistent functional/structural kidney injury. We identified molecular pathways underlying kidney injury and repair in ADHF and highlighted 31 novel candidate biomarkers for acute kidney injury in this setting.