The measurement of urinary flow is a vital medical indicator for critically ill patients in intensive care units. However, there is a clinical need to automate the real-time measurement of diuresis using Internet of Medical Things devices, allowing continuous monitoring of urine flow. A systematic review of scientific literature, patents, and available commercial products was conducted, leading to the conclusion that there is no suitable device to fulfill this need. We identified six characteristics that such a device should possess: minimizing contact with urine, detecting changes in flow patterns, the ability to record minute-by-minute data, capable of sending early alerts, not relying on exclusive disposable components, and being user-friendly for clinical professionals. Additionally, cost-effectiveness is crucial, encompassing the device, infrastructure, maintenance, and usage.

In the rat, oxytocin (OT) produces dose-dependent diuretic and natriuretic responses. Post-translational enzymatic conversion of the OT biosynthetic precursor forms both mature and C-terminally extended peptides. The plasma concentrations of these C-terminally extended peptides (OT-G; OT-GK and OT-GKR) are elevated in newborns and pregnant rats. Intravenous injection of OT-GKR to rats inhibits diuresis, whereas injection of amidated OT stimulates diuresis. Since OT and OT-GKR show different effects on the urine flow, we investigated whether OT-GKR modulates renal action by inhibition of the arginine-vasopressin (AVP) receptor V2 (V2R), the receptor involved in renal water reabsorption. Experiments were carried out in the 8-week-old Wistar rats receiving intravenous (iv) injections of vehicle, OT, OT-GKR or OT+OT-GKR combination. OT (10 μmol/kg) increased urine outflow by 40% (P<0.01) and sodium excretion by 47% (P<0.01). Treatment with OT-GKR (10 μmol/kg) decreased diuresis by 50% (P<0.001), decreased sodium excretion by 50% (P<0.05) and lowered potassium by 42% (P<0.05). OT antagonist (OTA) reduced diuresis and natriuresis exerted by OT, whereas the anti-diuretic effect of OT-GKR was unaffected by OTA. The treatment with V2R antagonist (V2A) in the presence and absence of OT induced diuresis, sodium and potassium outflow. V2A in the presence of OT-GKR only partially increased diuresis and natriuresis. Autoradiography and molecular docking analysis showed potent binding of OT-GKR to V2R. Finally, the release of cAMP from CHO cells overexpressing V2 receptor was induced by low concentration of AVP (EC50:4.2e-011), at higher concentrations of OT (EC50:3.2e-010) and by the highest concentrations of OT-GKR (EC50:1.1e-006). OT-GKR potentiated cAMP release when combined with AVP, but blocked cAMP release when combined with OT. These results suggest that OT-GKR by competing for the OT renal receptor (OTR) and binding to V2R in the kidney, induces anti-diuretic, anti-natriuretic, and anti-kaliuretic effects.

We established an IV outpatient diuresis (IVOiD) clinic and conducted a quality improvement project to evaluate safety, effectiveness and costs associated with outpatient versus inpatient diuresis for patients presenting with acute decompensated heart failure (ADHF) to the emergency department (ED).

The background of this study is to determine whether the addition of intravenous colloid to diuretic therapy, in comparison to diuretic therapy alone, improves diuresis and oxygenation and prevents intravascular volume depletion in intensive care unit (ICU) patients without shock.

The aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion.

Trimethylamine-oxide (TMAO) is present in seafood which is considered to be beneficial for health. Deep-water animals accumulate TMAO to protect proteins, such as lactate dehydrogenase (LDH), against hydrostatic pressure stress (HPS). We hypothesized that TMAO exerts beneficial effects on the circulatory system and protects cardiac LDH exposed to HPS produced by the contracting heart. Male, Sprague-Dawley and Spontaneously-Hypertensive-Heart-Failure (SHHF) rats were treated orally with either water (control) or TMAO. In vitro, LDH with or without TMAO was exposed to HPS and was evaluated using fluorescence correlation spectroscopy. TMAO-treated rats showed higher diuresis and natriuresis, lower arterial pressure and plasma NT-proBNP. Survival in SHHF-control was 66% vs 100% in SHHF-TMAO. In vitro, exposure of LDH to HPS with or without TMAO did not affect protein structure. In conclusion, TMAO reduced mortality in SHHF, which was associated with diuretic, natriuretic and hypotensive effects. HPS and TMAO did not affect LDH protein structure.

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently discovered rare disease caused by gain-of-function mutations of the V2 vasopressin receptor gene, AVPR2. To date, mutations of Phe229 and Arg137 have been identified as gain-of-function in the V2 vasopressin receptor (V2R). These receptor mutations lead to hyponatremia, which may lead to clinical symptoms in infants. Here we present a newly identified I130N substitution in exon 2 of the V2R gene in a family, causing NSIAD. This I130N mutation resulted in constitutive activity of the V2R with constitutive cyclic adenosine monophosphate (cAMP) generation in HEK293 cells. This basal activity could be blocked by the inverse agonist tolvaptan and arginine-vasopressin stimulation enhanced the cAMP production of I130N-V2R. The mutation causes a biased receptor conformation as the basal cAMP generation activity of I130N does not lead to interaction with β-arrestin. The constitutive activity of the mutant receptor caused constitutive dynamin-dependent and β-arrestin-independent internalization. The inhibition of basal internalization using dominant-negative dynamin resulted in an increased cell surface expression. In contrast to the constitutive internalization, agonist-induced endocytosis was β-arrestin dependent. Thus, tolvaptan could be used for treatment of hyponatremia in patients with NSIAD who carry the I130N-V2R mutation.

Fluid retention is a common complication of critical illness. It typically results from large-volume fluid infusions during acute resuscitation and is worsened by hypoalbuminemia. Recognized as edema, fluid retention is important for its association with delayed weaning and increased mortality. The standard treatment is the administration of diuretics, with or without albumin. We hypothesize that intravenous 25% albumin plus furosemide, by comparison with furosemide alone, improves diuresis, oxygenation, and hemodynamic stability in the deresuscitation of critically ill, hypoalbuminemic patients. We propose a pilot study to determine the feasibility of a trial to investigate this hypothesis.

Reduced glomerular filtration, hypertension and renal microvascular injury are hallmarks of chronic kidney disease, which has a global prevalence of ~10%. We have shown previously that the Fischer (F344) rat has lower GFR than the Lewis rat, and is more susceptible to renal injury induced by hypertension. In the early stages this injury is limited to the pre-glomerular vasculature. We hypothesized that poor renal hemodynamic function and vulnerability to vascular injury are causally linked and genetically determined. In the present study, normotensive F344 rats had a blunted pressure diuresis relationship, compared with Lewis rats. A kidney microarray was then interrogated using the Endeavour enrichment tool to rank candidate genes for impaired blood pressure control. Two novel candidate genes, P2rx7 and P2rx4, were identified, having a 7- and 3- fold increased expression in F344 rats. Immunohistochemistry localized P2X4 and P2X7 receptor expression to the endothelium of the pre-glomerular vasculature. Expression of both receptors was also found in the renal tubule; however there was no difference in expression profile between strains. Brilliant Blue G (BBG), a relatively selective P2X7 antagonist suitable for use in vivo, was administered to both rat strains. In Lewis rats, BBG had no effect on blood pressure, but increased renal vascular resistance, consistent with inhibition of some basal vasodilatory tone. In F344 rats BBG caused a significant reduction in blood pressure and a decrease in renal vascular resistance, suggesting that P2X7 receptor activation may enhance vasoconstrictor tone in this rat strain. BBG also reduced the pressure diuresis threshold in F344 rats, but did not alter its slope. These preliminary findings suggest a physiological and potential pathophysiological role for P2X7 in controlling renal and/or systemic vascular function, which could in turn affect susceptibility to hypertension-related kidney damage.

Patients with secondary adrenal insufficiency can present with impaired free water excretion and hyponatremia, which is due to the enhanced secretion of vasopressin (AVP) despite increased total body water. AVP is produced in magnocellular neurons in the paraventricular nucleus of the hypothalamus (PVH) and supraoptic nucleus and in parvocellular corticotropin-releasing factor (CRF) neurons in the PVH. This study aimed to elucidate whether magnocellular AVP neurons or parvocellular CRF neurons coexpressing AVP are responsible for the pathogenesis of hyponatremia in secondary adrenal insufficiency. The number of CRF neurons expressing copeptin, an AVP gene product, was significantly higher in adrenalectomized AVP-floxed mice (AVPfl/fl) than in sham-operated controls. Adrenalectomized AVPfl/fl mice supplemented with aldosterone showed impaired water diuresis under ad libitum access to water or after acute water loading. They became hyponatremic after acute water loading, and it was revealed under such conditions that aquaporin-2 (AQP2) protein levels were increased in the kidney. Furthermore, translocation of AQP2 to the apical membrane was markedly enhanced in renal collecting duct epithelial cells. Remarkably, all these abnormalities observed in the mouse model for secondary adrenal insufficiency were ameliorated in CRF-AVP-/- mice that lacked AVP in CRF neurons. Our study demonstrates that CRF neurons in the PVH are responsible for the pathogenesis of impaired water excretion in secondary adrenal insufficiency.

Background: Probenecid is a uricosuric agent that in addition to exerting a positive ionotropic effect in the heart, blocks the ATP transporter Pannexin 1 and inhibits the Cl-/HCO3- exchanger, pendrin. In the kidney, pendrin blunts the loss of salt wasting secondary to the inhibition of the thiazide-sensitive Na+-Cl- co-transporter (NCC/SLC12A3). Hypothesis: Pre-treatment with probenecid down-regulates pendrin; therefore, leaving NCC as the main salt absorbing transporter in the distal nephron, and hence enhances the hydrochlorothiazide (HCTZ)-induced diuresis. Methods: Daily balance studies, blood and urine chemical analysis, immunofluorescence, as well as western and northern blot analyses were utilized to examine the effects of probenecid alone (at 250 mg/kg/day) or in combination with HCTZ (at 40 mg/kg/day) on kidney function and on salt and water transporters in the collecting duct. Results: Male Sprague Dawley rats were subjected to three different protocols: (1) HCTZ for 4 days, (2) probenecid for 10 days, and (3) primed with probenecid for 6 days followed by probenecid and HCTZ for 4 additional days. Treatment protocol 1 (HCTZ for 4 days) only mildly increased the urine volume (U Vol) from a baseline of 9.8-13.4 ml/day. In response to treatment protocol 2 (probenecid for 10 days), U Vol increased to 15.9 ml/24 h. Treatment protocol 3 (probenecid for 6 days followed by probenecid and HCTZ for 4 additional days) increased the U Vol to 42.9 ml/day on day 4 of co-treatment with HCTZ and probenecid (compared to probenecid p = 0.003, n = 5 or HCTZ alone p = 0.001, n = 5). Probenecid treatment at 250 mg/kg/day downregulated the expression of pendrin and led to a decrease in AQP2 expression. Enhanced diuresis by probenecid plus HCTZ was not associated with volume depletion. Conclusion: Probenecid pre-treatment downregulates pendrin and robustly enhances diuresis by HCTZ-mediated NCC inhibition in kidney.

Growing evidence suggests that increased arginase activity affects vital bioprocesses in various systems and universally mediates the pathogenesis of numerous metabolic diseases. The adverse effects of arginase are associated with a severe decline in L-arginine bioavailability, which leads to nitric oxide synthase substrate insufficiency, uncoupling, and, eventually, superoxide anion generation and substantial reduction of nitric oxide (NO) synthesis. In cooperation, it contributes to chronic oxidative stress and endothelial dysfunction, which might lead to hypertension and atherosclerosis. Recent preclinical investigations point arginase as a promising therapeutic target in ameliorating metabolic and vascular dysfunctions. In the present study, adult rats with inherited stress-induced arterial hypertension (ISIAH) were used as a model of hypertension. Wistar rats served as normotensive controls. Experimental animals were intraperitoneally administered for seven days with nonproteinogenic amino acid L-norvaline (30 mg/kg/day), which is a potent arginase inhibitor, or with the vehicle. Blood pressure (BP), body weight, and diuresis were monitored. The changes in blood and urine levels of creatinine, urea, and NO metabolites were analyzed. We observed a significant decline in BP and induced diuresis in ISIAH rats following the treatment. The same procedure did not affect the BP of control animals. Remarkably, the treatment had no influence upon glomerular filtration rate in two experimental groups, just like the daily excretion of creatinine and urea. Conversely, NO metabolite levels were amplified in normotonic but not in hypertensive rats following the treatment. The data indicate that L-norvaline is a potential antihypertensive agent and deserves to be clinically investigated. Moreover, we suggest that changes in blood and urine are causally related to the effect of L-norvaline upon BP regulation.

Most of the filtered glucose is reabsorbed in the early proximal tubule by the sodium-glucose cotransporter SGLT2. The glycosuric effect of the SGLT2 inhibitor ipragliflozin is linked to a diuretic and natriuretic effect that activates compensatory increases in fluid and food intake to stabilize body fluid volume (BFV). However, the compensatory mechanisms that are activated on the level of renal tubules remain unclear. Type 2 diabetic Goto-Kakizaki (GK) rats were treated with vehicle or 0.01% (in diet) ipragliflozin with free access to fluid and food. After 8 weeks, GK rats were placed in metabolic cages for 24-hr. Ipragliflozin decreased body weight, serum glucose and systolic blood pressure, and increased fluid and food intake, urinary glucose and Na+ excretion, urine volume, and renal osmolar clearance, as well as urine vasopressin and solute-free water reabsorption (TcH2O). BFV, measured by bioimpedance spectroscopy, and fluid balance were similar among the two groups. Urine vasopressin in ipragliflozin-treated rats was negatively and positively associated with fluid balance and TcH2O, respectively. Ipragliflozin increased the renal membrane protein expression of SGLT2, aquaporin (AQP) 2 phosphorylated at Ser269 and vasopressin V2 receptor. The expression of SGLT1, GLUT2, AQP1, and AQP2 was similar between the groups. In conclusion, the SGLT2 inhibitor ipragliflozin induced a sustained glucosuria, diuresis, and natriuresis, with compensatory increases in fluid intake and vasopressin-induced TcH2O in proportion to the reduced fluid balance to maintain BFV. These results indicate that the osmotic diuresis induced by SGLT2 inhibition stimulates compensatory fluid intake and renal water reabsorption to maintain BFV.

Forced-diuresis during cardiopulmonary bypass (CPB) can be associated with significant electrolyte shifts. This study reports on the serum electrolyte changes during balanced forced-diuresis with the RenalGuard® system (RG) during CPB.

To investigate 50 week ultrasound imaging and ultrastructure changes of bladder in diuresis and diabetes rats.

The contribution of intrarenal alpha-2 adrenergic receptors in mediating the enhanced renal excretory responses evoked by the alpha-2-agonist xylazine was examined in a model of cirrhosis in rats. In sham-operated rats, xylazine (0.2 mg/kg, i.v.) increased diuresis and natriuresis (urine flow, control: 78 ± 12.1, 10 min: 155 ± 17, 20 min: 194 ± 19, 30 min: 146 ± 16, 40 min: 114 ± 13, 50 min: 95 ± 10.5 μl/min/g; urinary sodium excretion, control: 6.75 ± 2.08, 10 min: 7.12 ± 2.1, 20 min: 13.4 ± 4.6, 30 min: 14.6 ± 4.02, 40 min: 12.05 ± 2.35, 50 min: 12.7 ± 2.45 μeq/min/g), which was accompanied by a significant reduction in renal sympathetic nerve activity (RSNA) (control: 100, 10 min: 39.5 ± 5.8, 20 min: 53 ± 8.8, 30 min: 72 ± 7.0, 40 min: 83 ± 5.0, 50 min: 94 ± 6.1 AU). Xylazine (0.2 mg/kg) in cirrhotic animals, despite resulting in a significant reduction in RSNA (control: 100, 10 min: 73 ± 4.3*, 20 min: 70 ± 5.0*, 30 min: 76 ± 7.0*, 40 min: 85 ± 5.5*, 50 min: 92 ± 4.8* AU), was unable to increase natriuresis. A higher dose (20 mg/kg) of xylazine was not capable of increasing natriuresis and diuresis, even in the presence of a robust reduction in RSNA. Renal denervation did not alter the onset and time course of cirrhosis. The results indicated that during the development of cirrhosis, there is an adaptive process that disables the intrarenal alpha-2 adrenoceptor mechanisms that selectively promote water and urinary sodium excretion via a sympathetic renal nerve-independent mechanism. Thus, in cirrhotic rats, the diuresis/natriuresis induced by xylazine is independent on RSNA. Intrarenal and/or hormonal changes are probably involved in the impairment of xylazine-induced diuresis/natriuresis in cirrhosis.

Alpinia officinarum Hance (Zingiberaceae) has been used widely in traditional Chinese and Ayurvedic medicines. Its folkloric uses include relieving stomach ache, treating cold, improving the circulatory system, and reducing swelling. Its effectiveness and mechanism of antihypertension in obesity-induced hypertensive rats have not been studied yet as per our knowledge. This study has been designed to provide evidence of underlying mechanisms to the medicinal use of A. officinarum as a cardiotonic using an obesity-induced hypertension model in rats. Chronic administration of A. officinarum caused a marked reduction in the body weight gain and Lee index of rats compared to the obesogenic diet-fed rats. Its administration also caused attenuation in blood pressure (systolic, diastolic, and mean), serum total cholesterol, triglyceride, and leptin, while an increase in serum HDL and adiponectin levels was noticed. The catalase and superoxide dismutase enzymatic activities were found to be remarkable in the serum of A. officinarum-treated animal groups. A. officinarum showed mild to moderate diuretic, hepatoprotective, and reno-protective effects. The A. officinarum-treated group showed less mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase while the mRNA expression of peroxisome proliferator-activated receptor and mRNA expression of cholesterol 7 alpha-hydroxylase were raised in comparison to the hypertensive group of rats evaluated by quantitative real-time polymerase chain reaction. These findings show that A. officinarum possesses antihypertensive and diuretic activities, thus providing a rationale to the medicinal use of A. officinarum in cardiovascular ailments.

Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal sympathetic nerve activity that negates the diuresis and natriuresis as a negative feedback mechanism in normal rats. However, renal effects of GLP-1 in heart failure (HF) has not been elucidated. The present study was designed to assess GLP-1-induced diuresis and natriuresis in rats with HF and its interactions with renal nerve activity.

Background and Purpose: European Guidelines recommend early evaluation of diuresis and natriuresis after the first administration of diuretic to identify patients with insufficient diuretic response during acute heart failure. The aim of this work is to evaluate the prevalence and characteristics of patients with insufficient diuretic response according to this new algorithm. Methods: Prospective observational single centre study of consecutive patients with acute heart failure and congestive signs. Clinical evaluation, echocardiography and blood tests were performed. Diuretic naïve patients received 40 mg of intravenous furosemide. Patients on an oupatient diuretic regimen received 2 times the ambulatory dose. The diuresis volume was assessed 6 h after the first loop diuretic administration, and a spot urinary sample was taken after 2 h. Insufficient diuretic response was defined as natriuresis <70 mEq/L or diuresis volume <600 ml. Results: From January 2020 to December 2021, 73 patients were included (59% males, median age 76 years). Of these, 21 patients (28.8%, 95%CI 18.4; 39.2) had an insufficient diuretic response. Diuresis volume was <600 ml in 13 patients (18.1%), and 12 patients (16.4%) had urinary sodium <70 mEq/L. These patients had lower systolic blood pressure, worse glomerular filtration rate, and higher aldosterone levels. Ambulatory furosemide dose was also higher. These patients required more frequently thiazides and inotropes during admission. Conclusion: The diagnostic algorithm based on diuresis and natriuresis was able to detect up to 29% of patients with insufficient diuretic response, who showed some characteristics of more advanced disease.

Ceriops decandra (CD) and Ceriops tagal (CT) are two traditionally used mangrove plants widely distributed along the coastal areas of South Asia, Africa, South Pacific. In this study, we evaluated the diuretic potential of aerial roots of CD, CT and assessed the effectiveness of the plants' terpenoids enriched bioactive constituents against human carbonic anhydrase (hCA) enzyme through molecular docking.