Beef-on-dairy: Meat quality of veal and prediction of intramuscular fat using the Q-FOM™ Beef camera at the 5th-6th thoracic vertebra.

This study aims to describe the meat quality of young Holstein (HOL) beef-on-dairy heifers and bulls sired by Angus (ANG, n = 109), Charolais (CHA, n = 101) and Danish Blue (DBL, n = 127), and to investigate the performance of the handheld vision-based Q-FOM™ Beef camera in predicting the intramuscular fat concentration (IMF%) in M. longissimus thoracis from carcasses quartered at the 5th-6th thoracic vertebra. The results showed significant differences between crossbreeds and sexes on carcass characteristics and meat quality. DBL × HOL had the highest EUROP conformation scores, whereas ANG × HOL had darker meat with higher IMF% (3.52%) compared to CHA × HOL (2.99%) and DBL × HOL (2.51%). Bulls had higher EUROP conformation scores than heifers, and heifers had higher IMF% (3.70%) than bulls (2.31%). These findings indicate the potential for producing high-quality meat from beef-on-dairy heifers and ANG bulls. The IMF% prediction model for Q-FOM performed well with R2 = 0.91 and root mean squared error of cross validation, RMSECV = 1.33%. The performance of the prediction model on the beef-on-dairy veal subsample ranging from 0.9 to 7.4% IMF had lower accuracy (R2 = 0.48) and the prediction error (RMSEveal) was 1.00%. When grouping beef-on-dairy veal carcasses into three IMF% classes (2.5% IMF bins), 62.6% of the carcasses were accurately predicted. Furthermore, Q-FOM IMF% predictions and chemically determined IMF% were similar for each combination of sex and crossbreed, revealing a potential of Q-FOM IMF% predictions to be used in breeding, when aiming for higher meat quality.

Objective grading of rib eye traits using the Q-FOM™ camera in Australian beef carcasses.

The objective of this study was to develop calibration models against rib eye traits and independently validate the precision, accuracy, and repeatability of the Frontmatec Q-FOM™ Beef grading camera in Australian carcasses. This study compiled 12 different research datasets acquired from commercial processing facilities and were comprised of a diverse range of carcass phenotypes, graded by industry identified expert Meat Standards Australia (MSA) graders and sampled for chemical intramuscular fat (IMF%). Calibration performance was maintained when the device was independently validated. For continuous traits, the Q-FOM™ demonstrated precise (root mean squared error of prediction, RMSEP) and accurate (coefficient of determination, R2) prediction of eye muscle area (EMA) (R2 = 0.89, RMSEP = 4.3 cm2, slope = 0.96, bias = 0.7), MSA marbling (R2 = 0.95, RMSEP = 47.2, slope = 0.98, bias = -12.8) and chemical IMF% (R2 = 0.94, RMSEP = 1.56%, slope = 0.96, bias = 0.64). For categorical traits, the Q-FOM™ predicted 61%, 64.3% and 60.8% of AUS-MEAT marbling, meat colour and fat colour scores equivalent, and 95% within ±1 classes of expert grader scores. The Q-FOM™ also demonstrated very high repeatability and reproducibility across all traits.

Dietary sodium restriction reduces blood pressure in patients with treatment resistant hypertension.

PURPOSE: Patients with treatment resistant hypertension (TRH) are at particular risk of cardiovascular disease. Life style modification, including sodium restriction, is an important part of the treatment of these patients. We aimed to analyse if self-performed dietary sodium restriction could be implemented in patients with TRH and to evaluate the effect of this intervention on blood pressure (BP). Moreover, we aimed to examine if mechanisms involving nitric oxide, body water content and BNP, renal function and handling of sodium were involved in the effect on nocturnal and 24-h BP. Also, measurement of erythrocyte sodium sensitivity was included as a possible predictor for the effect of sodium restriction on BP levels. PATIENTS AND METHODS: TRH patients were included for this interventional four week study: two weeks on usual diet and two weeks on self-performed sodium restricted diet with supplementary handed out sodium-free bread. At the end of each period, 24-h BP and 24-h urine collections (sodium, potassium, ENaC) were performed, blood samples (BNP, NOx, salt blood test) were drawn, and bio impedance measurements were made. RESULTS: Fifteen patients, 11 males, with a mean age of 59 years were included. After sodium restriction, urinary sodium excretion decreased from 186 (70) to 91 [51] mmol/24-h, and all but one reduced sodium excretion. Nocturnal and 24-h systolic BP were significantly reduced (- 8 and - 10 mmHg, respectively, p < 0.05). NOx increased, BNP and extracellular water content decreased, all significantly. Change in NOx correlated to the change in 24-h systolic BP. BP response after sodium restriction was not related to sodium sensitivity examined by salt blood test. CONCLUSION: Self-performed dietary sodium restriction was feasible in a population of patients with TRH, and BP was significantly reduced. Increased NOx synthesis may be involved in the BP lowering effect of sodium restriction. TRIAL REGISTRATION: The study was registered in Clinical trials with ID: NCT06022133.

Bone Turnover, Mineralization, and Volume Estimated by 18F-Sodium Fluoride PET/CT and Biomarkers in Chronic Kidney Disease: Mineral and Bone Disorder Compared with Bone Biopsy.

INTRODUCTION: Invasive bone biopsy to assess bone metabolism in patients with chronic kidney disease-mineral and bone disorder may be replaced by the noninvasive 18F-NaF PET/CT and biomarkers of bone metabolism. We aimed to compare parameters of bone turnover, mineralization, and volume assessed by bone biopsies with results derived from 18F-NaF PET/CT and biomarkers (bone-specific alkaline phosphatase, osteocalcin, fibroblast growth factor 23, and osteoprotegerin). METHODS: A cross-sectional study included 17 dialysis patients, and results from 18F-NaF PET/CT scans and the biomarkers were directly compared with the results of histomorphometric analyses of tetracycline double-labeled trans-iliac bone biopsies. RESULTS: Bone biopsies showed 40% high, 20% normal, and 40% low bone turnover. No biopsies had generalized abnormal mineralization, and the bone volume/total tissue volume was low in 80% and high in 7%. The pelvic skeletal plasma clearance (Ki) from 18F-NaF PET/CT correlated with bone turnover parameters obtained by bone biopsy (activation frequency: r = 0.82, p < 0.01; bone formation rate/bone surface: r = 0.81, p < 0.01), and Ki defined low turnover with high sensitivity (83%) and specificity (100%). CT-derived radiodensity correlated with bone volume, r = 0.82, p < 0.01. Of the biomarkers, only osteocalcin showed a correlation with turnover assessed by histomorphometry. CONCLUSION: In conclusion, 18F-NaF PET/CT may be applicable for noninvasive assessment of bone turnover and volume in CKD-MBD.

Does conservative kidney management offer a quantity or quality of life benefit compared to dialysis? A systematic review.

BACKGROUND: Patients with stage 5 chronic kidney disease (CKD5) collaborate with their clinicians when choosing their future treatment modality. Most elderly patients with CKD5 may only have two treatment options: dialysis or conservative kidney management (CKM). The objective of this systematic review was to investigate whether CKM offers a quantity or quality of life benefit compared to dialysis for some patients with CKD5. METHODS: The databases MEDLINE, EMBASE, the Cochrane Library, and CINAHL were systematically searched for studies comparing patients with CKD5 who had chosen or were treated with either CKM or dialysis. The primary outcomes were mortality and quality of life (QoL). Hospitalization, symptom burden, and place of death were secondary outcomes. For studies reporting hazard ratios, pooled values were calculated, and forest plots conducted. RESULTS: Twenty-five primary studies, all observational, were identified. All studies reported an increased mortality in patients treated with CKM (pooled hazard ratio 0.47, 95 % confidence interval 0.34-0.65). For patients aged ≥ 80 years and for elderly individuals with comorbidities, results were ambiguous. In most studies, CKM seemed advantageous for QoL and secondary outcomes. Findings were limited by the heterogeneity of studies and biased outcomes favouring dialysis. CONCLUSIONS: In general, patients with CKD5 who have chosen or are on CKM live for a shorter time than patients who have chosen or are on dialysis. In patients aged ≥ 80 years old, and in elderly individuals with comorbidities, the survival benefits of dialysis seem to be lost. Regarding QoL, symptom burden, hospitalization, and place of death, CKM may have advantages. Higher quality studies are needed to guide patients and clinicians in the decision-making process.

Estimation of renal perfusion based on measurement of rubidium-82 clearance by PET/CT scanning in healthy subjects.

BACKGROUND: Changes in renal blood flow (RBF) may play a pathophysiological role in hypertension and kidney disease. However, RBF determination in humans has proven difficult. We aimed to confirm the feasibility of RBF estimation based on positron emission tomography/computed tomography (PET/CT) and rubidium-82 (82Rb) using the abdominal aorta as input function in a 1-tissue compartment model. METHODS: Eighteen healthy subjects underwent two dynamic 82Rb PET/CT scans in two different fields of view (FOV). FOV-A included the left ventricular blood pool (LVBP), the abdominal aorta (AA) and the majority of the kidneys. FOV-B included AA and the kidneys in their entirety. In FOV-A, an input function was derived from LVBP and from AA, in FOV-B from AA. One-tissue compartmental modelling was performed using tissue time activity curves generated from volumes of interest (VOI) contouring the kidneys, where the renal clearance of 82Rb is represented by the K1 kinetic parameter. Total clearance for both kidneys was calculated by multiplying the K1 values with the volume of VOIs used for analysis. Intra-assay coefficients of variation and inter-observer variation were calculated. RESULTS: For both kidneys, K1 values derived from AA did not differ significantly from values obtained from LVBP, neither were significant differences seen between AA in FOV-A and AA in FOV-B, nor between the right and left kidneys. For both kidneys, the intra-assay coefficients of variation were low (~ 5%) for both input functions. The measured K1 of 2.80 ml/min/cm3 translates to a total clearance for both kidneys of 766 ml/min/1.73 m2. CONCLUSION: Measurement of renal perfusion based on PET/CT and 82Rb using AA as input function in a 1-tissue compartment model is feasible in a single FOV. Based on previous studies showing 82Rb to be primarily present in plasma, the measured K1 clearance values are most likely representative of effective renal plasma flow (ERPF) rather than estimated RBF values, but as the accurate calculation of total clearance/flow is very much dependent on the analysed volume, a standardised definition for the employed renal volumes is needed to allow for proper comparison with standard ERPF and RBF reference methods.

Prolonging fixation time of an alternative fixative to formalin for dermatological samples using standard laboratory protocols.

AIMS: Though formalin remains to be the gold standard fixative in pathology departments, analytical challenges persist for nucleic acid evaluations. In our laboratory, formalin fixation of skin samples in particular impairs diagnostic accuracy and demands repetition of biopsies and analytical procedures. PAXgene Tissue Systems may be an alternative; however, according to manufacturer specifications it only allows fixation for 48 hours before having to add a stabiliser. This may be a challenge in laboratories, which are closed in weekends and bank holidays. Our aim was to validate this alternative fixative for dermatological samples with prolonged fixation times using standard laboratory protocols developed for formalin-fixed specimens. We compared the results with gold standard formalin fixation. METHODS: Skin specimens were formalin or PAXgene fixed for either 2 hours, 24 hours, 3 days or 7 days, paraffin-embedded, analysed and scored by observers. RESULTS: Generally, formalin outperformed PAXgene fixation in H&E stains and fluorescence in situ hybridisation (FISH), but both seem usable for diagnostics. Time of PAXgene fixation did not have an impact on alcian blue-Van Gieson (ABVG), H&E (p=0.48), nor immunohistochemistry (p=0.74). There was a tendency towards best PAXgene performance at 24 hours of fixation for FISH, and for DNA integrity analysis 24 hours or 3 days. CONCLUSIONS: Prolonging PAXgene fixation time to 3 days before adding stabiliser does not seem to have major impact on performance of general diagnostic analysis, but our preliminary results show optimisation of internal protocols are needed. PAXgene is an expensive alternative and may be confined to some dermatological samples.

Nocturnal blood pressure decrease in patients with chronic kidney disease and in healthy controls - significance of obstructive sleep apnea and renal function.

BACKGROUND: Chronic kidney disease (CKD) is often associated with a blunted nocturnal BP decrease and OSA. However, it is not fully clear whether a relationship exists between reduction in renal function and obstructive sleep apnea (OSA) on the one hand and relative nocturnal BP decrease in CKD patients on the other. The aim of this study was to investigate the association between nocturnal BP decrease and renal function, the degree of OSA, vasoactive hormones, and renal sodium handling in CKD3-4 patients and healthy age-matched controls. METHODS: We performed brachial and central 24-hour ambulatory BP measurement and CRM in 70 CKD3-4 patients and 56 controls. In plasma, we measured renin, AngII, aldosterone, and vasopressin. In urine, 24-hour excretion of sodium, protein fractions from the epithelial sodium channel (u-ENaCγ), and the AQP2 water channels (u-AQP2) were measured. RESULTS: CKD patients had lower relative nocturnal BP decrease than controls: brachial (10% vs 17%, P=0.001) and central (6% vs 10%, P=0.001). Moderate-to-severe OSA was more frequent in patients (15 vs 1%, P<0.0001). Neither the presence of OSA nor eGFR were predictors of either brachial or central nocturnal BP decrease. CKD3-4 nondippers were more obese, had higher HbA1c level, and more often a history of acute myocardial infarction than CKD3-4 dippers (P<0.05). CONCLUSION: CKD3-4 patients had lower brachial and central nocturnal BP decrease than healthy controls. OSA and eGFR were not associated with nondipping in CKD patients or healthy controls. Nondipping in CKD3-4 was associated with obesity, diabetes, and cardiovascular disease. CLINICALTRIALSGOV ID: NCT01951196.

A pilot study of muscle plasma protein changes after exercise.

INTRODUCTION: Creatine kinase (CK) and myoglobin (Mb) do not possess all good qualities as biomarkers of skeletal muscle damage. We investigated the utility of troponin I (TnI) and telethonin (Tcap) as markers and examined their temporal profiles after skeletal muscle damage. METHODS: Plasma profiles were measured before and after exercise in 3 groups: subjects affected by either Becker muscular dystrophy or McArdle disease, and healthy subjects. RESULTS: Mb and TnI appeared early in the blood, and the increase of TnI was only observed in patients with muscle disease. The CK increase was more delayed in plasma. Tcap was not detectable at any time. CONCLUSIONS: Our results suggest that TnI is a marker of more severe damage signifying sarcomeric damage, and it could therefore be an important supplement to CK and Mb in clinical practice. Tcap is not useful as a marker for skeletal muscle damage.

Effect of amiloride and spironolactone on renal tubular function and central blood pressure in patients with arterial hypertension during baseline conditions and after furosemide: a double-blinded, randomized, placebo-controlled crossover trial.

This study demonstrates that the increased potassium content in the body seems to change both the blood pressure and renal tubular function. We wanted to test the hypotheses that amiloride and spironolactone induced potassium retention reduces ambulatory blood pressure (ABP) and central blood pressure (CBP) during baseline conditions and after furosemide and that the tubular transport via the epithelial sodium channels (ENaCs) and aquaporin-2 (AQP2) water channels was increased by furosemide in arterial hypertension. Each of three 28-day treatment periods (placebo, amiloride, and spironolactone) was completed by a 4-day period with standardized diet regarding calories and sodium and water intake. At the end of each period, we measured pulse wave velocity (PWV), central systolic blood pressure (CSBP), central diastolic blood pressure (CDBP), glomerular filtration rate (GFR), free water clearance (CH2O), fractional excretion of sodium (FENa) and potassium (FEK), urinary excretion of AQP2 (u-AQP2), urinary excretion of γ-fraction of the ENaC (u-ENaCγ), and plasma concentrations of renin (PRC), angiotensin II (p-Ang II), and aldosterone (p-Aldo) at baseline conditions and after furosemide bolus. Ambulatory blood pressure and CBP were significantly lowered by amiloride and spironolactone. During 24-hour urine collection and at baseline, GFR, CH2O, FENa, FEK, u-AQP2 and u-ENaCγ were the same. After furosemide, CH2O, FENa, FEK, u-AQP2, u-ENaCγ, PRC, p-Ang II, p-Aldo, PWV and CDBP increased after all treatments. However, during amiloride treatment, FEK increased to a larger extent than after spironolactone and during placebo after furosemide, and CSBP was not significantly reduced. The increases in water and sodium absorption via AQP2 and ENaC after furosemide most likely are compensatory phenomena to antagonize water and sodium depletion. Amiloride is less effective than spironolactone to reduce renal potassium excretion.

Effect of amiloride and spironolactone on renal tubular function, ambulatory blood pressure, and pulse wave velocity in healthy participants in a double-blinded, randomized, placebo-controlled, crossover trial.

We wanted to test the hypothesis that treatment with amiloride or spironolactone reduced ambulatory (ABP) and central blood pressure (CBP) and that tubular transport via ENaCγ and AQP2 was increased after furosemide treatment. During baseline conditions, there were no differences in ABP, CBP, renal tubular function, or plasma concentrations of vasoactive hormones. After furosemide treatment, an increase in CBP, CH(2)o, FE(Na), FE(K), u-AQP2/min, u-ENaCγ/min, PRC, p-Ang II, and p-Aldo was observed. The increases in water and sodium absorption via AQP2 and ENaC after furosemide treatment most likely are compensatory phenomena to antagonize water and sodium depletion.

Abnormal increase in urinary aquaporin-2 excretion in response to hypertonic saline in essential hypertension.

BACKGROUND: Dysregulation of the expression/shuttling of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in renal collecting duct principal cells has been found in animal models of hypertension. We tested whether a similar dysregulation exists in essential hypertension. METHODS: We measured urinary excretion of AQP2 and ENaC ß-subunit corrected for creatinine (u-AQP2(CR), u-ENaC(ß-CR)), prostaglandin E2 (u-PGE2) and cyclic AMP (u-cAMP), fractional sodium excretion (FE(Na)), free water clearance (C(H2O)), as well as plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), and atrial and brain natriuretic peptide (ANP, BNP) in 21 patients with essential hypertension and 20 normotensive controls during 24-h urine collection (baseline), and after hypertonic saline infusion on a 4-day high sodium (HS) diet (300 mmol sodium/day) and a 4-day low sodium (LS) diet (30 mmol sodium/day). RESULTS: At baseline, no differences in u-AQP2(CR) or u-ENaC(ß-CR) were measured between patients and controls. U-AQP2(CR) increased significantly more after saline in patients than controls, whereas u-ENaC(ß-CR) increased similarly. The saline caused exaggerated natriuretic increases in patients during HS intake. Neither baseline levels of u-PGE2, u-cAMP, AVP, PRC, Ang II, Aldo, ANP, and BNP nor changes after saline could explain the abnormal u-AQP2(CR) response. CONCLUSIONS: No differences were found in u-AQP2(CR) and u-ENaC(ß-CR) between patients and controls at baseline. However, in response to saline, u-AQP2(CR) was abnormally increased in patients, whereas the u-ENaC(ß-CR) response was normal. The mechanism behind the abnormal AQP2 regulation is not clarified, but it does not seem to be AVP-dependent. Clinicaltrial.gov identifier: NCT00345124.

Urinary excretion of AQP2 and ENaC in autosomal dominant polycystic kidney disease during basal conditions and after a hypertonic saline infusion.

Renal handling of sodium and water is abnormal in chronic kidney diseases. To study the function and regulation of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in autosomal dominant polycystic kidney disease (ADPKD), we measured urinary excretion of AQP2 (u-AQP2), the ß-subunit of ENaC (u-ENaC(ß)), cAMP (u-cAMP), and prostaglandin E(2) (u-PGE(2)); free water clearance (C(H2O)); fractional sodium excretion (FE(Na)); and plasma vasopressin (p-AVP), renin (p-Renin), angiotensin II (p-ANG II), aldosterone (p-Aldo), and atrial and brain natriuretic peptide (p-ANP, p-BNP) in patients with ADPKD and healthy controls during 24-h urine collection and after hypertonic saline infusion during high sodium intake (HS; 300 mmol sodium/day) and low sodium intake (LS; 30 mmol sodium/day). No difference in u-AQP2, u-ENaC(ß), u-cAMP, u-PGE(2), C(H2O), and vasoactive hormones was found between patients and controls at baseline, but during HS the patients had higher FE(Na). The saline caused higher increases in FE(Na) in patients than controls during LS, but the changes in u-ENaC(ß), p-Aldo, p-ANP, p-BNP, p-Renin, and p-ANG II were similar. Higher increases in u-AQP2 and p-AVP were seen in patients during both diets. In conclusion, u-AQP2 and u-ENaC(ß) were comparable in patients with ADPKD and controls at baseline. In ADPKD, the larger increase in u-AQP2 and p-AVP in response to saline could reflect an abnormal water absorption in the distal nephron. During LS, the larger increase in FE(Na) in response to saline could reflect a defective renal sodium retaining capacity in ADPKD, unrelated to changes in u-ENaC(ß).

Effect of potassium supplementation on renal tubular function, ambulatory blood pressure and pulse wave velocity in healthy humans.

BACKGROUND: Potassium is the main intracellular cation, which contributes to keeping the intracellular membrane potential slightly negative and elicits contraction of smooth, skeletal and cardiac muscle. A change in potassium intake modifies both cardiovascular and renal tubular function. The purpose of the trial was to investigate the effect of dietary potassium supplementation, 100 mmol daily in a randomized, placebo-controlled, crossover trial of healthy participants during two periods of 28 days duration. The participants (N = 21) received a diet that was standardized regarding energy requirement, and sodium and water intake. METHODS: 24-hour ambulatory blood pressure (ABP) and applanation tonometry were used to assess blood pressure, pulse wave velocity (PWV), augmentation index (AIx) and central blood pressure (CBP). Immunoassays were used for measurements of plasma concentrations of vasoactive hormones: renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP), vasopressin (AVP), pro-brain natriuretic peptide (pro-BNP),endothelin (Endo), urinary excretions of aquaporin 2 (AQP2), cyclic AMP (cAMP), and the ß-fraction of the epithelial sodium channel (ENaC(ß)). RESULTS: AQP2 excretion increased during potassium supplementation, and free water clearance fell. The changes in urinary potassium excretion and urinary AQP2 excretion were significantly and positively correlated. Aldo increased. GFR, u-ENaC- ß, PRC, Ang II, ANP, BNP, Endo, blood pressure and AI were not significantly changed by potassium supplementation, whereas PWV increased slightly. CONCLUSIONS: Potassium supplementation changed renal tubular function and increased water absorption in the distal part of the nephron. In spite of an increase in aldosterone in plasma, blood pressure remained unchanged after potassium supplementation.

No difference between alfacalcidol and paricalcitol in the treatment of secondary hyperparathyroidism in hemodialysis patients: a randomized crossover trial.

Alfacalcidol and paricalcitol are vitamin D analogs used for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease, but have known dose-dependent side effects that cause hypercalcemia and hyperphosphatemia. In this investigator-initiated multicenter randomized clinical trial, we originally intended two crossover study periods with a washout interval in 86 chronic hemodialysis patients. These patients received increasing intravenous doses of either alfacalcidol or paricalcitol for 16 weeks, until parathyroid hormone was adequately suppressed or calcium or phosphate levels reached an upper threshold. Unfortunately, due to a period effect, only the initial 16-week intervention period for 80 patients was statistically analyzed. The proportion of patients achieving a 30% decrease in parathyroid hormone levels over the last four weeks of study was statistically indistinguishable between the two groups. Paricalcitol was more efficient at correcting low than high baseline parathyroid hormone levels, whereas alfacalcidol was equally effective at all levels. There were no differences in the incidence of hypercalcemia and hyperphosphatemia. Thus, alfacalcidol and paricalcitol were equally effective in the suppression of secondary hyperparathyroidism in hemodialysis patients while calcium and phosphorus were kept in the desired range.

The effect of eprosartan on reflex sympathetic activation in sodium restricted patients with essential hypertension.

AT(1) receptor antagonists possess sympathoinhibitory effects in animal experiments, but in human studies the results are conflicting. We tested the hypothesis that very short-term treatment with the AT(1) receptor antagonist eprosartan inhibits reflex activation of the sympathetic nervous system in sodium-restricted patients with essential hypertension. The effect of eprosartan on urinary sodium and lithium excretion, heart rate, blood pressure, and vasoactive hormones was measured during reflex activation of the sympathetic nervous system by a cold pressor test and by a sodium nitroprusside induced 10 mm Hg reduction of the mean arterial pressure. It was a randomized, placebo-controlled, double-blinded, crossover study in 14 patients with essential hypertension. Glomerular filtration rate and renal tubular function were determined with continuous infusion clearance technique and vasoactive hormones with radioimmunoassays. Eprosartan had no effect on the increases in heart rate and plasma levels of noradrenaline during reflex activation of the sympathetic nervous system. However, eprosartan significantly decreased in fractional excretions of sodium (mean ± SD) (0.23 ± 0.22%) and lithium (3.1 ± 1.7%) during the sodium nitroprusside infusion, compared to placebo. Very short-term eprosartan treatment does not seem to have any sympathoinhibitory effects in sodium restricted patients with essential hypertension.

Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels.

BACKGROUND: Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels. METHODS: The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2), the beta-fraction of the epithelial sodium channel (u-ENaCbeta), cyclic-AMP (u-cAMP), prostaglandin E2 (u-PGE2). Free water clearance (CH2O), fractional excretion of sodium (FENa), and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide. RESULTS: Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher. CONCLUSION: During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system TRIAL REGISTRATION: Clinical Trials Identifier: NCT00281762.

Abnormal function of the vasopressin-cyclic-AMP-aquaporin2 axis during urine concentrating and diluting in patients with reduced renal function. A case control study.

BACKGROUND: The kidneys ability to concentrate and dilute urine is deteriorated during progressive renal insufficiency. We wanted to test the hypothesis that these phenomena could be attributed to an abnormal function of the principal cells in the distal part of the nephron. METHODS: Healthy control subjects and patients with chronic kidney diseases were studied. Group 1 comprised healthy subjects, n = 10. Groups 2-4 comprised patients with chronic kidney disease (Group 2, n = 14, e-GFR ≤ 90 m1/min; Group 3, n = 11, 60 m1/min ≤ e-GFR < 90 ml/min; and Group 4, n = 16, 15 ml/min ≤ e-GFR < 60 ml/min). The subjects collected urine during 24 hours. A urine concentrating test was done by thirsting during the following 12 hours. Thereafter, a urine diluting test was performed with a water load of 20 ml/kg body weight. The effect variables were urinary excretions of aquaporin2 (u-AQP2), cyclic-AMP (u-c-AMP), urine volume (UV), free water clearance (CH2O), urine osmolarity (u-Osm), and plasma arginine vasopressin (p-AVP). RESULTS: After fluid deprivation, u-Osm increased. In all groups, UV and CH2O decreased and u-AQP2 and u-c-AMP increased in Groups 1 and 2, but were unchanged in Group 3 and 4. P-AVP was significantly higher in Group 4 than in the other groups. During urine diluting, UV and CH2O reached significantly higher levels in Groups 1-3 than Group 4. Both before and after water loading, u-AQP2 and p-AVP were significantly higher and u-c-AMP was significantly lower in Group 4 than the other groups. Estimated-GFR was correlated negatively to p-AVP and positively to u-c-AMP. CONCLUSIONS: Patients with moderately severe chronic kidney disease have a reduced renal concentrating and diluting capacity compared to both patients with milder chronic kidney disease and healthy control subjects. These phenomena can be attributed, at least partly, to an abnormally decreased response in the AVP-c-AMP-AQP2 axis.ClinicalTrials.Gov Identifier: NCT00313430.

Protein-enriched diet increases water absorption via the aquaporin-2 water channels in healthy humans.

BACKGROUND: According to animal experiments, a protein-enriched diet increased renal absorption of sodium and water. We wanted to test the hypothesis that a protein-enriched diet would increase the expression of the aquaporin-2 water channels and the epithelial sodium channels in the distal part of the nephron using biomarkers for the activity of the two channels. METHODS: We performed a randomized, placebo controlled crossover study in 13 healthy humans to examine the effect of a protein-enriched diet on renal handling of water and sodium during baseline condition and during hypertonic saline infusion. We measured the effect of the protein-enriched diet on urinary excretions of aquaporin-2 (u-AQP2), the beta-fraction of the epithelial sodium channels (u-ENaC(beta)), free water clearance (C(H2O)), fractional excretion of sodium and vasoactive hormones. RESULTS: During baseline conditions, u-AQP2 increased, and C(H2O) decreased during the protein-enriched diet, whereas u-ENaC(beta) was unchanged, although the urinary sodium excretion increased. During hypertonic saline infusion, the response in the effect variables did not deviate between protein-enriched and normal diet. Plasma concentrations of angiotensin II and aldosterone increased as well as pulse rate. Vasopressin in plasma was unchanged, and prostaglandin E(2) fell during the protein-enriched diet. CONCLUSIONS: The protein-enriched diet increased water absorption via an increased transport via the aquaporin-2 water channels. The increased u-AQP2 might be due to a reduced prostaglandin level. The increase in renal sodium excretion seems to be mediated in another part of the nephron than the epithelial sodium channels.