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Sodium is the main osmotically active ion in the extracellular fluid and its concentration goes hand in hand with fluid volume. Under physiological conditions, homeostasis of sodium and thus amount of fluid is regulated by neural and humoral interconnection of body tissues and organs. Both heart and kidneys are crucial in maintaining volume status. Proper kidney function is necessary to excrete regulated amount of water and solutes and adequate heart function is inevitable to sustain renal perfusion pressure, oxygen supply etc. As these organs are bidirectionally interconnected, injury of one leads to dysfunction of another. This condition is known as cardiorenal syndrome. It is divided into five subtypes regarding timeframe and pathophysiology of the onset. Hemodynamic effects include congestion, decreased cardiac output, but also production of natriuretic peptides. Renal congestion and hypoperfusion leads to kidney injury and maladaptive activation of renin-angiotensin-aldosterone system and sympathetic nervous system. In cardiorenal syndromes sodium and water excretion is impaired leading to volume overload and far-reaching negative consequences, including higher morbidity and mortality of these patients. [ABSTRACT FROM AUTHOR]

IntroductionThis study was designed to measure the concentration and activity of urinary proteases that activate renal epithelial sodium channel (ENaC) mediated Na+ transport in infants with congenital heart disease, a potential mechanism for fluid retention.MethodsUrine samples from infants undergoing cardiac surgery were collected at three time points: T1) pre-operatively, T2) 6–8 h after surgery, and T3) 24 h after diuretics. Urine was collected from five heathy infant controls. The urine was tested for four proteases and whole-cell patch-clamp testing was conducted in renal collecting duct M-1 cells to test whether patient urine increased Na+ currents consistent with ENaC activation.ResultsHeavy chain of plasminogen, furin, and prostasin were significantly higher in cardiac patients prior to surgery compared to controls. There was no difference in most proteases before and after surgery. Urine from cardiac patients produced a significantly greater increase in Na+ inward currents compared to healthy controls.ConclusionUrine from infants with congenital heart disease is richer in proteases and has the potential to increase activation of ENaC in the nephron to enhance Na+ reabsorption, which may lead to fluid retention in this population.

Fouling and slagging are intractable ash-related problems for boilers burning high-sodium coals (HSC) to produce electricity or heat. Reduction and resource utilization of solid waste, coal gangues, is urgent because of stringent environmental regulations and economic benefits. Based on the sodium-rich character of Zhundong coal (ZDC) and the mineralogical features of the coal gangues (ZDG), this work investigated their co-firing performance, the sodium retention behaviors as well as the slagging and fouling tendency of the ashes. Results show that combustion performance of ZDC is not reduced despite ofthe lower reactivity of ZDG. The co-firing reaction follows the 3D diffusion model (cylinder symmetry) which probably reflects the gas diffusion of oxygen to combustible matter. During co-firing, the enriched silica and alumina components in ZDG efficiently react with the alkali and alkaline earth metals (sodium, magnesium and calcium) in ZDC to form complex minerals, thus effectively capturing and retaining sodium. The slagging and fouling propensity of ashes are notably reduced. Overall, co-firing provides an alternative means to solve the ash slagging and fouling issues, and also for the reduction and resource utilization of coal gangues. [ABSTRACT FROM AUTHOR]

Sodium retention and edema are hallmarks of nephrotic syndrome (NS). Different experimental rodent models have been established for simulating NS, however, not all of them feature sodium retention which requires proteinuria to exceed a certain threshold. In rats, puromycin aminonucleoside nephrosis (PAN) is a classic NS model introduced in 1955 that was adopted as doxorubicin‐induced nephropathy (DIN) in 129S1/SvImJ mice. In recent years, mice with inducible podocin deletion (Nphs2Δipod) or podocyte apoptosis (POD‐ATTAC) have been developed. In these models, sodium retention is thought to be caused by activation of the epithelial sodium channel (ENaC) in the distal nephron through aberrantly filtered serine proteases or proteasuria. Strikingly, rodent NS models follow an identical chronological time course after the development of proteinuria featuring sodium retention within days and spontaneous reversal thereafter. In DIN and Nphs2Δipod mice, inhibition of ENaC by amiloride or urinary serine protease activity by aprotinin prevents sodium retention, opening up new and promising therapeutic approaches that could be translated into the treatment of nephrotic patients. However, the essential serine protease(s) responsible for ENaC activation is (are) still unknown. With the use of nephrotic rodent models, there is the possibility that this (these) will be identified in the future. This review summarizes the various rodent models used to study experimental nephrotic syndrome and the insights gained from these models with regard to the pathophysiology of sodium retention. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is an independent risk factor for the development of cerebrovascular disease, particularly small vessel disease which can manifest in a variety of phenotypes ranging from lacunes to microbleeds. Small vessel disease likely contributes to cognitive dysfunction in the CKD population. Non-traditional risk factors for vascular injury in uremia include loss of calcification inhibitors, hyperphosphatemia, increased blood pressure variability, elastinolysis, platelet dysfunction, and chronic inflammation. In this review, we discuss the putative pathways by which these mechanisms may promote cerebrovascular disease and thus increase risk of future stroke in CKD patients.

Albumin infusions improve circulatory and renal function in patients with decompensated cirrhosis. However, there is no convincing evidence that hypoalbuminemia contributes to ascites formation in liver cirrhosis. The aim of our study is to determine the exact role of hypoalbuminemia in the formation of ascites caused by liver cirrhosis and its underlying mechanism. Clinical profiles of patients with liver cirrhosis retrospectively analyzed. The details of albumin involved in ascites formation were investigated in rat model and murine model. Statistical analysis demonstrated hypoalbuminemia was an independent risk factor for ascites formation in patients with liver cirrhosis (OR = 0.722, P < 0.001). In carbon tetrachloride (CCl 4)-induced rat model of liver cirrhosis, a significant reduction in serum albumin was observed in rats with ascites (13.37 g/L) compared with rats without ascites (21.43 g/L, P < 0.001). In thioacetamide (TAA)-treated mice, ascites amount of heterozygous albumin (Alb+/−) mice (112.0 mg) was larger than that of wild-type (Alb+/+) mice (58.46 mg, P < 0.001). In CCl 4 -induced chronic liver injury, ascites amounts of Alb+/− or Alb+/+ mice were 80.00 mg or 48.46 mg (P = 0.001). Further study demonstrated 24-h urinary sodium excretion in Alb+/− mice was lower than that of Alb+/+ mice in TAA/CCl 4 -induce murine models of liver cirrhosis. Additionally, serum sodium concentration of Alb+/− mice was lower than that of Alb+/+ mice. In cirrhotic mice, higher level of antidiuretic hormone was observed in Alb+/− mice compared with the control; and renal aquaporin (AQP2) expression in Alb+/− mice was significantly higher than that of WT mice. These revealed hypoalbuminemia contributed to the occurrence of ascites in liver cirrhosis through sodium and water retention. • Hypoalbuminemia was an independent risk factor for cirrhotic ascites formation in patients. • Albumin deficient mice demonstrated causal relationship between hypoalbuminemia and ascites in cirrhotic mice. • Hypoalbuminemia contributed to cirrhotic ascites through sodium and water retention. [ABSTRACT FROM AUTHOR]

L'insuffisance cardiaque se définit par une inaptitude de la pompe cardiaque à assurer un débit cardiaque adéquat dans les conditions normales, elle est très répandue en population gériatrique. Le diagnostic est évoqué par l'examen clinique, confirmé par la radio du thorax, l'échocardiographie et les valeurs plasmatiques des peptides natriurétiques. Le traitement de l'insuffisance cardiaque chronique comprend l'éducation des patients et une thérapie pharmacologique stable ayant pour objectif de lutter efficacement contre l'activation des systèmes neuro-hormonaux. Heart failure is defined by an inability of the heart pump to ensure adequate cardiac output under normal conditions, it is very resistant in the geriatric population. The diagnosis is suggested by clinical examination, confirmed by chest x-ray, echocardiography, and plasma values of natriuretic peptides. The treatment of chronic heart failure includes patient education and stable pharmacological therapy aimed at effectively combating the activation of neurohormonal systems. [ABSTRACT FROM AUTHOR]

Background The gut‐derived hormone GLP‐1 (glucagon‐like peptide‐1) exerts beneficial effects against established risk factors for chronic kidney disease. GLP‐1 influences renal function by stimulating diuresis and natriuresis and thus lowering arterial blood pressure. The role of the sympathetic nervous system has been implicated as an important link between obesity with elevated arterial pressure and chronic kidney disease. The primary aim of this study was to determine the contribution of renal sympathetic nerves on intrapelvic GLP‐1‐mediated diuresis and natriuresis in high‐fat diet (HFD)‐induced obese rats. Methods and Results Obesity was induced in rats by HFD for 12 weeks, followed by either surgical bilateral renal denervation or chronic subcutaneous endopeptidase neprilysin inhibition by sacubitril for a week. Diuretic and natriuretic responses to intrapelvic administration of the GLP‐1R (GLP‐1 receptor) agonist exendin‐4 were monitored in anesthetized control and HFD rats. Renal GLP‐1R expression and neprilysin expression and activity were measured. The effects of norepinephrine on the expression of GLP‐1R and neprilysin in kidney epithelial LLC‐PK1 cells were also examined. We found that diuretic and natriuretic responses to exendin‐4 were significantly reduced in the HFD obese rats compared with the control rats (cumulative urine flow at 40 minutes, 387±32 versus 650±65 µL/gkw; cumulative sodium excretion at 40 minutes, 42±5 versus 75±10 µEq/gkw, P

Background: Ventilator-induced lung injury (VILI) via respiratory mechanics is deeply interwoven with hemodynamic, kidney and fluid/electrolyte changes. We aimed to assess the role of positive fluid balance in the framework of ventilation-induced lung injury.Methods:Post-hoc analysis of seventy-eight pigs invasively ventilated for 48 h with mechanical power ranging from 18 to 137 J/min and divided into two groups: high vs. low pleural pressure (10.0 ± 2.8 vs. 4.4 ± 1.5 cmH2O; p < 0.01). Respiratory mechanics, hemodynamics, fluid, sodium and osmotic balances, were assessed at 0, 6, 12, 24, 48 h. Sodium distribution between intracellular, extracellular and non-osmotic sodium storage compartments was estimated assuming osmotic equilibrium. Lung weight, wet-to-dry ratios of lung, kidney, liver, bowel and muscle were measured at the end of the experiment.Results: High pleural pressure group had significant higher cardiac output (2.96 ± 0.92 vs. 3.41 ± 1.68 L/min; p < 0.01), use of norepinephrine/epinephrine (1.76 ± 3.31 vs. 5.79 ± 9.69 mcg/kg; p < 0.01) and total fluid infusions (3.06 ± 2.32 vs. 4.04 ± 3.04 L; p < 0.01). This hemodynamic status was associated with significantly increased sodium and fluid retention (at 48 h, respectively, 601.3 ± 334.7 vs. 1073.2 ± 525.9 mmol, p < 0.01; and 2.99 ± 2.54 vs. 6.66 ± 3.87 L, p < 0.01). Ten percent of the infused sodium was stored in an osmotically inactive compartment. Increasing fluid and sodium retention was positively associated with lung-weight (R2 = 0.43, p < 0.01; R2 = 0.48, p < 0.01) and with wet-to-dry ratio of the lungs (R2 = 0.14, p < 0.01; R2 = 0.18, p < 0.01) and kidneys (R2 = 0.11, p = 0.02; R2 = 0.12, p = 0.01).Conclusion: Increased mechanical power and pleural pressures dictated an increase in hemodynamic support resulting in proportionally increased sodium and fluid retention and pulmonary edema.

Background: Ventilator-induced lung injury (VILI) via respiratory mechanics is deeply interwoven with hemodynamic, kidney and fluid/electrolyte changes. We aimed to assess the role of positive fluid balance in the framework of ventilation-induced lung injury. Methods: Post-hoc analysis of seventy-eight pigs invasively ventilated for 48 h with mechanical power ranging from 18 to 137 J/min and divided into two groups: high vs. low pleural pressure (10.0 ± 2.8 vs. 4.4 ± 1.5 cmH2O; p < 0.01). Respiratory mechanics, hemodynamics, fluid, sodium and osmotic balances, were assessed at 0, 6, 12, 24, 48 h. Sodium distribution between intracellular, extracellular and non-osmotic sodium storage compartments was estimated assuming osmotic equilibrium. Lung weight, wet-to-dry ratios of lung, kidney, liver, bowel and muscle were measured at the end of the experiment. Results: High pleural pressure group had significant higher cardiac output (2.96 ± 0.92 vs. 3.41 ± 1.68 L/min; p < 0.01), use of norepinephrine/epinephrine (1.76 ± 3.31 vs. 5.79 ± 9.69 mcg/kg; p < 0.01) and total fluid infusions (3.06 ± 2.32 vs. 4.04 ± 3.04 L; p < 0.01). This hemodynamic status was associated with significantly increased sodium and fluid retention (at 48 h, respectively, 601.3 ± 334.7 vs. 1073.2 ± 525.9 mmol, p < 0.01; and 2.99 ± 2.54 vs. 6.66 ± 3.87 L, p < 0.01). Ten percent of the infused sodium was stored in an osmotically inactive compartment. Increasing fluid and sodium retention was positively associated with lung-weight (R 2 = 0.43, p < 0.01; R 2 = 0.48, p < 0.01) and with wet-to-dry ratio of the lungs (R 2 = 0.14, p < 0.01; R 2 = 0.18, p < 0.01) and kidneys (R 2 = 0.11, p = 0.02; R 2 = 0.12, p = 0.01). Conclusion: Increased mechanical power and pleural pressures dictated an increase in hemodynamic support resulting in proportionally increased sodium and fluid retention and pulmonary edema. [ABSTRACT FROM AUTHOR]

Aim: Sodium retention is the hallmark of nephrotic syndrome (NS) and mediated by the proteolytic activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases. Plasmin is highly abundant in nephrotic urine and has been proposed to be the principal serine protease responsible for ENaC activation in NS. However, a proof of the essential role of plasmin in experimental NS is lacking. Methods: We used a genetic mouse model of NS based on an inducible podocin knockout (Bl6‐Nphs2tm3.1Antc*Tg(Nphs1‐rtTA*3G)8Jhm*Tg(tetO‐cre)1Jaw or nphs2Δipod). These mice were crossed with plasminogen deficient mice (Bl6‐Plgtm1Jld or plg−/−) to generate double knockout mice (nphs2Δipod*plg−/−). NS was induced after oral doxycycline treatment for 14 days and mice were followed for subsequent 14 days. Results: Uninduced nphs2Δipod*plg−/− mice had normal kidney function and sodium handling. After induction, proteinuria increased similarly in both nphs2Δipod*plg+/+ and nphs2Δipod*plg−/− mice. Western blot revealed the urinary excretion of plasminogen and plasmin in nphs2Δipod*plg+/+ mice which were absent in nphs2Δipod*plg−/− mice. After the onset of proteinuria, amiloride‐sensitive natriuresis was increased compared to the uninduced state in both genotypes. Subsequently, urinary sodium excretion dropped in both genotypes leading to an increase in body weight and development of ascites. Treatment with the serine protease inhibitor aprotinin prevented sodium retention in both genotypes. Conclusions: This study shows that mice lacking urinary plasminogen are not protected from ENaC‐mediated sodium retention in experimental NS. This points to an essential role of other urinary serine proteases in the absence of plasminogen. [ABSTRACT FROM AUTHOR]

Abstract Background Liver cirrhosis is characterized by avid sodium retention where the activation of the renin angiotensin aldosterone system (RAAS) is considered to be the hallmark of the sodium retaining mechanisms. The direct effect of angiotensin II (ANGII) on the AT-1 receptor in the proximal tubules is partly responsible for the sodium retention. The aim was to estimate the natriuretic and neurohumoral effects of an ANGII receptor antagonist (losartan) in the late phase of the disease in a rat model of liver cirrhosis. Methods Bile duct ligated (BDL) and sham operated rats received 2 weeks of treatment with losartan 4 mg/kg/day or placebo, given by gastric gavage 5 weeks after surgery. Daily sodium and potassium intakes and renal excretions were measured. Results The renal sodium excretion decreased in the BDL animals and this was not affected by losartan treatment. At baseline the plasma renin concentration (PRC) was similar in sham and BDL animals, but increased urinary excretion of ANGII and an increase P-Aldosterone was observed in the placebo treated BDL animals. The PRC was more than 150 times higher in the losartan treated BDL animals (p

In liver cirrhosis, renin‐angiotensin system (RAS) activation sustains renal sodium retention and hepatic fibrogenesis. New information has recently enlivened the traditional concept of RAS. For instance, renin and prorenin bind their ubiquitous receptors, resulting in the local production of angiotensin (Ang) II; increased serum calcium and calcimimetic agents, through stimulation of extracellular calcium‐sensing receptors (CaSR), blunt renin production and lead to natriuretic effects in human and experimental cirrhosis. Alongside systemic production, there is Ang II tissue production within various organs through RAS enzymes different from angiotensin‐converting enzyme (ACE), that is chymase, tissue plasminogen activator and several cathepsins. In experimental cirrhosis, inhibition of chymase leads to natriuretic and hepatic antifibrotic effects, without changes in systemic haemodynamics. In the kidney, local RAS coordinates proximal and distal tubular sodium reabsorption. However, renalase, whose plasma and tissue levels are severely altered in experimental cirrhosis, degrades systemic and renal tubule catecholamines, antagonizing the effects of renal RAS. Angiotensinogen‐derived natriuretic and vasodilating peptides (Ang1‐9, Ang1‐7, Ang3‐8) and their receptors have been described. Receptor agonists or antagonists are available to affect portal hypertension and sodium retention in cirrhosis. ACE2‐dependent generation of Ang1‐7 may inhibit experimental liver fibrosis. inhibition of Ang1‐7 clearance by means of neprilysin blockade has portal hypotensive and natriuretic effects. Ang1‐12, whose production renin does not regulate, is converted to several different angiotensin peptides via chymase. Finally, Ang II behaves as either an antinatriuretic or a natriuretic agent, based on the tissue content of AT1R and AT2R receptors, their ratio being prone to pharmacological modulation. [ABSTRACT FROM AUTHOR]

The suppression of adrenergic and renin-angiotensin-aldosterone system (RAAS) activity, exaggerated due to hypoperfusion-related hypoxia and/or sodium retention, is crucial for drugs' efficacy in heart failure (HF). Both, insufficient oxygenation and excess sodium impair the glycocalyx-dependent microcroperfusion and peripheral metabolism, therefore enhancing the adrenergic and RAAS activity. The local renal and pulmonary RAAS activity and hypoxia increase sodium retention. Interstitial sodium accumulation activates interstitial inflammation and coagulation disorders that further diminish glycocalyx-supported microperfusion and peripheral metabolism. The main trigger of glycocalyx damage in reduced ejection fraction (EF) HF is hypoxia; whereas, in HF preserved EF sodium retention prevails; both stimulate left ventricular (LV) cardiac output (CO), however, impair microperfusion and metabolic heat production. Infrared-dependent, surface-induced flow (SIF) and diamagnetic properties of oxygenated haemoglobin; both improve non-Newtonian blood flow. Therefore, the temperature-driven SIF augments the deoxygenated erythrocytes' flow, while the pulmonary oxygenation of haemoglobin, by diamagnetic properties, enables frictionless erythrocytes' flow in the oxygenated blood compartments complementing the cardiac function in HF. [ABSTRACT FROM AUTHOR]

Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule. We examined literature data including those coming from our group regarding the role of oxidative stress and sodium retention in CNIs induced hypertension and their involvement in cardiovascular-renal remodeling. Based on the available data, we have provided support to the activation of RhoA/Rho kinase pathway as an important effector in the pathophysiology of CNIs induced post-transplant hypertension via activation of oxidative stress and sodium retention. Clarification of how the biochemical and molecular mechanisms that regulate the processes involved in CNIs induced post transplant hypertension work and interact, would provide further insights not only into the comprehension of the pathophysiology of CNIs induced post transplant hypertension but could also have a positive impact on the clinical ground through the identification of significant targets. Their specific pharmacologic targeting might have multiple beneficial effects on the whole cardiovascular-renal function. The demonstration that in kidney transplanted patients with CNIs induced post-transplanted hypertension, the treatment of hypertension with different antihypertensive drugs inducing a comparable blood pressure reduction but different effects for example on oxidative stress and oxidative stress related proteins and/or Rho kinase and sodium retention, could be helpful for the choice of the antihypertensive treatment in these patients which takes advantage from effects of these drugs beyond blood pressure reduction.

Introduction: This study was designed to measure the concentration and activity of urinary proteases that activate renal epithelial sodium channel (ENaC) mediated Na + transport in infants with congenital heart disease, a potential mechanism for fluid retention., Methods: Urine samples from infants undergoing cardiac surgery were collected at three time points: T1) pre-operatively, T2) 6-8 h after surgery, and T3) 24 h after diuretics. Urine was collected from five heathy infant controls. The urine was tested for four proteases and whole-cell patch-clamp testing was conducted in renal collecting duct M-1 cells to test whether patient urine increased Na + currents consistent with ENaC activation., Results: Heavy chain of plasminogen, furin, and prostasin were significantly higher in cardiac patients prior to surgery compared to controls. There was no difference in most proteases before and after surgery. Urine from cardiac patients produced a significantly greater increase in Na + inward currents compared to healthy controls., Conclusion: Urine from infants with congenital heart disease is richer in proteases and has the potential to increase activation of ENaC in the nephron to enhance Na + reabsorption, which may lead to fluid retention in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Ortmann, Nandi, Li, Zheng and Patel.)

The characteristics of the soil in the Peninsula of Yucatán confer unique organoleptic properties to the habanero pepper (Capsicum chinense Jacq.), and thus this entity possesses the denomination of origin of the species, making these chilis the most coveted, nationally and internationally. However, the extreme microtopographic variation distinguishing the Peninsula complicates the transfer of technologies and the successful establishment of agricultural practices. Maya farmers of the region identify the brown soils as preferable for the cultivation of this chili, although there is some controversy among the farmers regarding the best yields when the quality of the water used for irrigation is poor. No studies of the effect of soil type on this plant have been carried out. This work evaluated the impact of three types of soil of the Peninsula (red, brown, and black) on growth, fruit production, and nutrient content in soils and plants, during different phenological stages. The results indicate that the red and brown soils were the best for the growth and production of the fruit. In the black soil, it was possible to observe greater retention and accumulation of sodium applied in the water used for irrigation and in the macronutrients N, P, K, which may have led to a negative effect in the development of the fruit in these plants. Moreover, the plants growing in red and brown soils seem to make a more efficient use of the nutrients, presenting higher values of N, P, and K in their tissues in the flowering-fructification stage. These results are particularly useful in the realization of agricultural plans with a lower consumption of fertilizers, which allows an increase in yield, particularly if we take into account the enormous problems of saline intrusion worldwide and in this region. [ABSTRACT FROM AUTHOR]

Background: Tissue sodium content by 23Na magnetic resonance imaging (MRI) has been found to be increased in arterial hypertension. We analyzed whether tissue sodium content is increased in patients with type-2 diabetes (T2DM).Methods: Patients with T2DM were compared to those with primary hypertension. Patients with T2DM were off any antidiabetic and hypertensive patients off any antihypertensive therapy for at least 4 weeks. Skin and muscle sodium content was assessed non-invasively with a 3.0 T clinical MRI system (Magnetom Verio, Siemens Health Care, Erlangen, Germany) in each patient.Results: In patients with T2DM (N = 59) we observed significantly greater muscle sodium content (diabetes: 20.6 ± 3.5 vs hypertension: 16.3 ± 2.5 mmol/l, p < 0.001) and skin sodium content (diabetes: 24.5 ± 7.2 vs hypertension: 20.6 ± 5.7 mmol/l, p = 0.01) than in those with primary hypertension (N = 33). When potential confounders (age, body mass index, gender, systolic and diastolic blood pressure, estimated glomerular filtration rate) were entered in a covariance analysis, both skin sodium content (p = 0.037) and muscle sodium content (p < 0.001) were still clearly elevated.Conclusion: Patients with T2DM have greater skin and muscle sodium content. These are the first known data to demonstrate increased tissue sodium content in patients with T2DM, measured by 23Na magnetic resonance imaging. Since tissue sodium content is related to organ damage, therapeutic intervention should aim at reducing tissue sodium content. [ABSTRACT FROM AUTHOR]

Introduction: Ascites commonly complicates cirrhosis, becoming refractory to treatment with diuretics and sodium restriction in approximately 10% of patients. Pathogenesis of refractory ascites (RA) is multifactorial, the common final pathway being renal hypoperfusion and avid sodium retention. Refractory ascites has a negative prognostic implication in the natural history of cirrhosis. Management of RA include sodium restriction and regular large volume paracentesis (LVP) with albumin infusions, preventing paracentesis-induced circulatory dysfunction. In appropriate setting, transjugular intrahepatic porto-systemic shunt (TIPS) can be considered. Ascites clearance with TIPS can lead to nutritional improvement, avoiding sarcopenia. Liver transplantation (LT) remains the definitive treatment for eligible candidates. Areas covered: Our review summarizes current updates on pathogenesis and clinical management of RA including potential future therapeutic options such as the automated slow-flow ascites pump, chronic outpatient albumin infusion and cell-free and concentrated ascites reinfusion therapy. Expert commentary: Standard of care in patients with RA include LVP with albumin replacement and prompt referral for LT where indicated. Other novel therapeutic options on the horizon include automated low-flow ascites pump and cell-free, concentrated albumin reinfusion therapy. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that Angiotensin II (Ang II) is a contributing factor to the response pattern in African Americans (AAs) who retain rather than excrete sodium during mental stress.Design/study Participants: Double-blind, randomized, cross-over trial of 87 healthy AAs aged 18 to 50 years.Interventions: The study participants received either a placebo or irbesartan, (150 mg PO), an Ang II receptor antagonist, for seven days prior to stress testing. Urinary sodium excretion (UNaV) and systolic blood pressure (SBP) were collected prior to and throughout a mental stress protocol (rest and stress period).Setting: A southeastern university.Main Outcome Measures: Ang II, SBP, and sodium retention.Results: During the placebo condition, 62 participants showed the expected increase in UNaV (excreters) while 25 participants reduced UNaV during stress (retainers). Irbesartan retainers demonstrated a reversal in the direction of their natriuretic response, now increasing UNaV in response to stress (∆ UNaV of -.094 mmol/min with placebo vs .052 mmol/min on irbesartan; P<.001). In excreters, irbesartan reduced SBP levels during both rest (-2.36 mm Hg; P=.03) and stress (-4.59;P<.0001), and an even more pronounced reduction in SBP was demonstrated by retainers on treatment during both rest (-4.29 mm Hg; P=.03) and stress (-6.12; P<.001).Conclusions: Ang II contributes to sodium retention in retainers. Furthermore, our findings indicate that suppression of Ang II has a beneficial effect on SBP during rest and stress in this population. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Recent work has demonstrated that activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases causes sodium retention in nephrotic syndrome. The aim of this study was to elucidate a potential role of plasma kallikrein (PKLK) as a candidate serine protease in this context. Methods: We analysed PKLK in the urine of patients with chronic kidney disease (CKD, n = 171) and investigated its ability to activate human ENaC expressed in Xenopus laevis oocytes. Moreover, we studied sodium retention in PKLK‐deficient mice (klkb1−/−) with experimental nephrotic syndrome induced by doxorubicin injection. Results: In patients with CKD, we found that PKLK is excreted in the urine up to a concentration of 2 μg mL−1 which was correlated with albuminuria (r = .71) and overhydration as assessed by bioimpedance spectroscopy (r = .44). PKLK increased ENaC‐mediated whole‐cell currents, which was associated with the appearance of a 67 kDa γ‐ENaC cleavage product at the cell surface consistent with proteolytic activation. Mutating a putative prostasin cleavage site in γ‐ENaC prevented channel stimulation by PKLK. In a mouse model for nephrotic syndrome, active PKLK was present in nephrotic urine of klkb1+/+ but not of klkb1−/− mice. However, klkb1−/− mice were not protected from ENaC activation and sodium retention compared to nephrotic klkb1+/+ mice. Conclusion: Plasma kallikrein is detected in the urine of proteinuric patients and mice and activates ENaC in vitro involving the putative prostasin cleavage site. However, PKLK is not essential for volume retention in nephrotic mice. [ABSTRACT FROM AUTHOR]

Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal reninangiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule. We examined literature data including those coming from our group regarding the role of oxidative stress and sodium retention in CNIs induced hypertension and their involvement in cardiovascular-renal remodeling. Based on the available data, we have provided support to the activation of RhoA/Rho kinase pathway as an important effector in the pathophysiology of CNIs induced post-transplant hypertension via activation of oxidative stress and sodium retention. Clarification of how the biochemical and molecular mechanisms that regulate the processes involved in CNIs induced post transplant hypertension work and interact, would provide further insights not only into the comprehension of the pathophysiology of CNIs induced post transplant hypertension but could also have a positive impact on the clinical ground through the identification of significant targets. Their specific pharmacologic targeting might have multiple beneficial effects on the whole cardiovascular-renal function. The demonstration that in kidney transplanted patients with CNIs induced post-transplanted hypertension, the treatment of hypertension with different antihypertensive drugs inducing a comparable blood pressure reduction but different effects for example on oxidative stress and oxidative stress related proteins and/ or Rho kinase and sodium retention, could be helpful for the choice of the antihypertensive treatment in these patients which takes advantage from effects of these drugs beyond blood pressure reduction. [ABSTRACT FROM AUTHOR]

Objective: To compare the dose dependent effect of chloroform extract of aloe vera gel on sodium and water retention in rats with indomethacin and control. Methodology: This randomized controlled trial was conducted at Post Graduate Medical Institute, Lahore in which thirty male Sprague Dawley rats were divided in to five groups. First group was control (CTL), second was given indomethacin 3 mg/kg (INDO) while groups AVL, AVM, and AVH were given 200, 400 and 800 mg/kg doses of Aloe vera gel extract orally for a period of 28 days. Body weight, blood haematocrit level, total sodium excretion and serum sodium and potassium concentrations were measured. SPSS version 17 was used for data analysis. Results: Comparison of treatment groups with control at end of study showed significant weight gain in group INDO and AVH (p value <0.001). INDO and AVH groups also showed a significant decrease in total sodium excretion (p value 0.001 and 0.015). The mean haematocrit decreased insignificantly in groups INDO and AVH, while serum sodium level increased insignificantly in group INDO. Highest serum potassium level was observed in group INDO (p value 0.001) and the lowest was found in group AVH but difference was not significant as compared to control. Conclusion: High dose of aloe vera gel extract causes significant sodium and water retention in healthy rats, which was still less than that of indomethacin. [ABSTRACT FROM AUTHOR]

Ascites is the most common complication associated with cirrhosis resulting in poor quality of life, high risk of development of other complications of cirrhosis, increased morbidity and mortality associated with surgical interventions, and poor long-term outcome. Patients with cirrhosis and a first onset of ascites, have a probability of survival of 85% during the first year and 56% at 5 years without liver transplantation. Ascites is caused due to increased renal sodium retention as a result of increased activity of the renin-angiotensinaldosterone system in response to marked vasodilation of the splanchnic circulation. The practical management of ascites involves the proper evaluation of a patient with a thorough history and physical exam. In addition, complete laboratory, ascitic fluid, and radiological tests should be performed. One of the most important steps in the initial assessment of patients with ascites is to refer the appropriate candidates for liver transplantation, as it offers a definitive cure for cirrhosis and its complications. While the initial management of uncomplicated ascites with low sodium diet and diuretic treatment is straightforward in a majority of patients, approximately 10% of patients fail to respond to diuretics and become a real therapeutic challenge. The initial treatment of choice in patients with refractory ascites is large-volume paracentesis (LVP) associated with intravenous albumin; some patients also benefit from transjugular intrahepatic portosystemic shunts (TIPS). When repeated LVP or TIPS cannot be performed, other approaches using vasoconstrictors such as midodrine can be considered although data are scarce. A newly designed automated low flow pump system (Alfapump), which is designed to move ascites from the peritoneal cavity to the urinary bladder where it is eliminated spontaneously through diuresis is promising, but the data are also limited and safety is still a matter of concern. This article focuses on the practical aspects of the evaluation and treatment of patients with ascites and cirrhosis and also discusses how to translate our current understanding of ascites pathophysiology into new treatment methods for patients with fluid retention. [ABSTRACT FROM AUTHOR]

Background: The effects of sodium–glucose co-transporter type 2 inhibitors on home blood pressure were examined in type 2 diabetes with nephropathy. Methods: The patients with diabetic nephropathy were screened from medical records in our hospitals. Among them, 52 patients who measured home blood pressure and started to take sodium–glucose co-transporter type 2 inhibitors were selected. Clinical parameters including estimated glomerular filtration rate, albuminuria and home blood pressure for 6 months were analysed. Results: Sodium–glucose co-transporter type 2 inhibitors (luseogliflozin 5 mg/day or canagliflozin 100 mg/day) reduced body weight, HbA1c, albuminuria, estimated glomerular filtration rate and office blood pressure. Although sodium–glucose co-transporter type 2 inhibitors did not alter morning blood pressure, it reduced evening systolic blood pressure. Regression analyses revealed that decreases in evening blood pressure predicted decrements in albuminuria. Conclusion: The present data suggest that sodium–glucose co-transporter type 2 inhibitors suppress sodium overload during daytime to reduce evening blood pressure and albuminuria. [ABSTRACT FROM AUTHOR]

Epidemiological and experimental studies have led to the hypothesis of the fetal origin of adult diseases, suggesting that some adult diseases might be determined before birth by altered fetal development. Maternal diabetes subjects the fetus to an adverse environment that has been demonstrated to result in metabolic, cardiovascular and renal impairment in the offspring. The growing amount of obesity in young females in developed and some developing countries should contribute to increasing the incidence of diabetes among pregnant women. In this review, we discuss how renal and extrarenal mechanisms participate in the genesis of hypertension induced by a diabetic status during fetal development.

Patients with advanced cirrhosis have abnormal sodium homoeostasis. The study was undertaken to quantify the sodium transport across the plasma membrane of red blood cells ( RBC) in patients with cirrhosis. RBC efflux and influx of sodium were studied in vitro with tracer 22Na+ according to linear kinetics in 24 patients with cirrhosis and 14 healthy controls. The sodium efflux was modified by ouabain (O), furosemide (F) and a combination of O and F (O + F). RBC sodium was significantly decreased (4·6 versus control 6·3 mmol l−1, P<0·001) and directly related to serum sodium ( r = 0·57, P<0·05). The RBC fractional sodium efflux was higher in patients with cirrhosis (+46%, P<0·01) compared to controls. Inhibition in both high (145 mmol l−1)- and low (120 mmol l−1)-sodium buffers showed that the F-insensitive sodium efflux was twice as high in cirrhosis as in controls ( P = 0·03-0·007), especially the O-sensitive, F-insensitive efflux was increased (+ 225%, P = 0·01-0·006). Fractional F-sensitive transport was normal in cirrhosis. RBC sodium influx was largely normal in cirrhosis. In conclusion, RBC sodium content is reduced in patients with cirrhosis with a direct relation to serum sodium. Increased RBC sodium efflux is especially related to ouabain-sensitive, furosemide-insensitive transport and thus most likely due to upregulated activity of the sodium-potassium pump. The study gives no evidence to an altered intracellular/extracellular sodium ratio or to a reduced fractional furosemide-sensitive sodium transport in cirrhosis. [ABSTRACT FROM AUTHOR]