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Postexercise hydration is fundamental to replace fluid loss from sweat. This study evaluated rehydration and gastrointestinal (GI) symptoms for each of three beverages: water (W), sports drink (SD), and skimmed, lactose-free milk (SLM) after moderate-intensity cycling in the heat. Sixteen college students completed three exercise sessions each to lose ≈2% of their body mass. They drank 150% of body mass loss of the drink assigned in randomized order; net fluid balance, diuresis, and GI symptoms were measured and followed up for 3 hr after completion of fluid intake. SLM showed higher fluid retention (∼69%) versus W (∼40%; p <.001); SD (∼56%) was not different from SLM or W (p >.05). Net fluid balance was higher for SLM (−0.26 kg) and SD (−0.42 kg) than W (−0.67 kg) after 3 hr (p <.001), resulting from a significantly lower diuresis with SLM. Reported GI disturbances were mild and showed no difference among drinks (p >.05) despite ingestion of W (1,992 ± 425 ml), SD (1,999 ± 429 ml), and SLM (1,993 ± 426 ml) in 90 min. In conclusion, SLM was more effective than W for postexercise rehydration, showing greater fluid retention for the 3-hr follow-up and presenting with low-intensity GI symptoms similar to those with W and SD. These results confirm that SLM is an effective option for hydration after exercise in the heat. [ABSTRACT FROM AUTHOR]

The targeted activation or inhibition of specific cell populations using chemogenetics allows the precise dissection of cellular signaling and function. Designer receptors exclusively activated by designer drugs (DREADDs) is a chemogenetic platform initially developed by mutating human muscarinic receptors to be unresponsive to endogenous acetylcholine but exclusively activated by an "inert" designer drug. Compound 21 (C21) is a new and potent DREADD agonist; however, radioligand assays from a recent report indicated its ability to bind to endogenous G protein-coupled receptors (GPCRs), including muscarinic M1–3 receptors. Whether this binding causes off-target effects is unclear. Renal innervation is important for the regulation of renal function, and the advent of chemogenetic tools provides significant opportunities for the mechanistic understanding of renal innervation and function. GPCRs such as adrenergic and muscarinic receptors play a role in renal function; thus, a careful pharmacological characterization of C21 in renal function is a prerequisite for this approach. Unexpectedly, an infusion of 1.0 mg/kg C21 in anesthetized mice caused an ∼4-fold increase in urine output and correspondingly increased the glomerular filtration rate (GFR), suggesting a C21-mediated acute diuretic effect. This acute diuresis effect was further confirmed in awake mice using voiding spot assays. The exact molecular mechanism for C21-mediated diuresis is unclear; however, we demonstrated by in vitro myography that C21 can effectively inhibit bladder smooth muscle contraction by antagonizing M3 receptors at the micromolar level, causing increased voiding size in vivo. In summary, C21 functions as a GPCR antagonist and has significant dose-dependent off-target effects in the renal system. [ABSTRACT FROM AUTHOR]

Background: Hyponatraemia is a prevalent electrolyte disturbance observed in critically ill patients. The rapid correction of low plasma sodium levels by continuous renal replacement therapy (CRRT) carries the risk of developing osmotic demyelination syndrome (ODS), which can be prevented by implementing an individualized CRRT method. Aim: This study aims to introduce a CRRT protocol for the safe and gradual correction of severe hyponatraemia. Study Design: This retrospective case series study was conducted in an intensive care unit (ICU). All four patients with severe hyponatraemia (<125 mmol/L) and renal failure between October 1, 2022, and September 30, 2023, were treated by CRRT with sterile water and regional citrate anticoagulation (RCA). Data on patient demographics, laboratory biochemical parameters, urine outputs and CRRT‐related adverse events were collected. Laboratory parameters and urine outputs were compared by paired t‐tests before and after CRRT. Results: After CRRT, sodium levels were significantly increased (112.7 ± 6.7 vs. 141.9 ± 2.8 mmol/L, p =.005). Abnormal urine outputs, potassium, creatinine and bicarbonate were corrected (p for all <.05). Safe and gradual correction of hyponatraemia and internal environmental dysregulation was achieved in all patients without any complications related to CRRT, particularly ODS. Conclusion: It is a novel and simple strategy to correct severe hyponatraemia effectively while ensuring the safety of patients that can be easily implemented by experienced nurse staff. Relevance to Clinical Practice: The sterile water‐based protocol for postfilter dilution is safe to correct severe hyponatraemia with RCA and can be easily performed by experienced critical care nurses according to the precalculated formula. CRRT‐trained, experienced ICU nurses are competent to initiate and adjust sterile water infusion discretely to prevent overcorrection of hyponatraemia. [ABSTRACT FROM AUTHOR]

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple approaches have been tried to achieve adequate decongestion rapidly while minimizing adverse effects, no single diuretic strategy has shown superiority, and there is a paucity of data and guidelines to utilize in making these decisions. Observational cohort studies have shown associations between urine sodium excretion and outcomes after hospitalization for ADHF. Urine chemistries (urine sodium ± urine creatinine) may guide diuretic titration during ADHF, and multiple randomized clinical trials have been designed to compare a strategy of urine chemistry–guided diuresis to usual care. This review will summarize current literature for diuretic monitoring and titration strategies, outline evidence gaps, and describe the recently completed and ongoing clinical trials to address these gaps in patients with ADHF with a particular focus on the utility of urine sodium–guided strategies. [ABSTRACT FROM AUTHOR]

Background: Positron emission tomography (PET) with 18F-FDG is being used more frequently to evaluate primary pelvic tumors (PTs). However, a standardized hydration protocol is essential for an optimal diuretic effect and constant results. Methods: We reviewed 109 patients with PTs who had undergone 18F-FDG PET/CT examinations between November 2006 and April 2013. Four different protocols were used: (a) no hydration (group 1); (b) oral hydration (800 mL) after an early scan (group 2); (c) intravenous (IV) hydration (500 mL) during an early scan followed by oral hydration (800 mL) and IV furosemide (20 mg) after an early scan (group 3); and (d) oral hydration (800 mL) before an FDG injection followed by the protocol from group 3 (group 4). The maximum standardized uptake (SUVmax) of the urinary bladder (UB) and PTs and the PT/UB SUVmax ratios were examined. Results: The UB SUVmax of group 4 was significantly lower in the early scan compared to that in the other three groups. Group 4 had a significantly higher PT/UB SUVmax ratio in the early scan than the other three groups, and it also had a 52.5% positivity rate for PTs. Conclusions: The pre-hydration plus forced diuresis protocol yielded the optimal effect of UB radiotracer washout and had the best PT/UB SUVmax ratio in both scans. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a multifactorial syndrome with a high risk of short- and long-term complications as well as increased health care costs. The traditional biomarkers of AKI, serum creatinine and urine output, have important limitations. The discovery of new functional and damage/stress biomarkers has enabled a more precise delineation of the aetiology, pathophysiology, site, mechanisms, and severity of injury. This has allowed earlier diagnosis, better prognostication, and the identification of AKI sub-phenotypes. In this review, we summarize the roles and challenges of these new biomarkers in clinical practice and research. [ABSTRACT FROM AUTHOR]

Background: Lower urinary tract symptoms (LUTSs) are a common complaint in adult and elderly men with bladder outlet obstruction, and have a considerable impact on their quality of life. Symptoms affect storage, voiding and post micturition stages. Among the latter, a feeling of incomplete emptying is one of the most bothersome for the patients; a condition that in turn contributes to affect urinary urgency, nocturia and frequency. Common recommendations include self-management practices (e.g., control of fluid intake, double-voiding and distraction techniques) to relieve patients' symptoms, whose effectiveness, however, is under debate. Methods: In this report we describe two pioneering procedures to favor bladder residual content voiding in people complaining of LUTS disorders. The first is based on motor imagery and the second on the use of odors. The beneficial effects of Mental imagery techniques on various tasks (e.g., in the treatment of several pathological conditions or as valid mnemonics aids have a long tradition and have received consistently experimental support. Thus, a patient (a 68-year-old Caucasian man) complaining of LUTS was trained to use a motor imagery technique (building up a visual image comprising the bladder, the detrusor muscle and the urethra, and to imagine the detrusor muscle contracting and the flow of urine expelled) for 90 days and two odors (coffee and a lavender scented cleanser) for 10 days, as a trigger for micturition. He was asked to record—immediately after the first morning micturition—the time interval between the first (free) and the second (cued) micturition. Results: Reported data suggest the efficacy of motor imagery in favoring the bladder residual urine voiding in a few minutes (M = 4.75 min.) compared to the control condition, i.e., the baseline of the patient (M = 79.5 min.), while no differences between the odor-based procedures (M 1st odorant = 70.6 min.; M 2nd odorant = 71.1 min) and the latter were observed. Conclusions: A procedure based on an imagery technique may, therefore, be of general value—as a suggested protocol—and accordingly can be applicable to clinical settings. An olfactory bladder control hypothesis cannot, however, be ruled out and is discussed as a promising future line of research. [ABSTRACT FROM AUTHOR]

Introduction: Mannitol, an osmotic diuretic solution, is commonly utilized in priming cardiopulmonary bypass (CPB) and can impact kidney function. This study was conducted to investigate the impact of mannitol use during CPB on kidney function in patients undergoing coronary artery bypass surgery. Methods: This randomized, double-blind clinical trial studied 90 patients undergoing coronary artery bypass surgery. In the control group (n=45), the prime solution included Ringer's lactate, and in the intervention group (n=45), the prime solution had 200 ml of mannitol 20% and Ringer's lactate. A P -value<0.05 was considered significant. The primary endpoint of this study is renal function. Results: Demographic characteristics and risk factors were not significantly different between the two groups (P >0.05). Additionally, there was no statistically significant difference between two groups in terms of CPB time, aortic cross-clamp time, length of time connected to mechanical ventilation, 30-day mortality, ICU, and hospital stay time (P >0.05). Furthermore, no statistically significant difference was observed between the two groups in serum creatinine levels (P =0.53) or BUN levels (P =0.13). The study also found no statistically significant difference in the diuresis rate between the two groups (P =0.10). Conclusion: The present study has shown that adding mannitol to the prime has no effect on kidney function, length of time connected to mechanical ventilation, length of stay in the ICU, or 30-day mortality. Therefore, it suggests that mannitol cannot be used as a preventative strategy for acute kidney injury after cardiac surgery. [ABSTRACT FROM AUTHOR]

Ilaj bit Tadbeer, a vital therapeutic approach in the Unani system of medicine, focuses on modifying six essential elements to restore health. This approach encompasses various regimenal therapies such as cupping (Hijāma), leeching (Ta'līq or irsal-e- 'Alaq), venesection (Fasd), massage (Dalk), irrigation (Natūl), emesis (Qay'), diuresis (Idrār-i-Bawl), diaphoresis (Tariq), concoction and purgation (Mundij and Mu'shil therapy), medicated steam (Bukhoor), cauterization (Kaiyy), and enema (Huqna). Fasd is a crucial regimen in Ilaj Bit Tadbeer, serving as a method to eliminate morbid material from the body to treat diseases or maintain good health. With a history of almost 3000 years, Fasd has been effectively utilized in treating various ailments across different eras. Although venesection, or Fasd, has a historical significance, its modern application has declined due to the lack of scientific validation. This review aims to explore the historical context, therapeutic applications, contraindications, and contemporary scientific evidence of Fasd, emphasizing its potential in modern medicine. [ABSTRACT FROM AUTHOR]

Acute heart failure (AHF) often leads to unfavorable outcomes due to fluid overload. While diuretics are the cornerstone treatment, acetazolamide may enhance diuretic efficiency by reducing sodium reabsorption. We performed a systematic review and meta-analysis on the effects of acetazolamide as an add-on therapy in patients with AHF compared to diuretic therapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCT). A random-effects model was employed to compute mean differences and risk ratios. Statistical analysis was performed using R software. The GRADE approach was used to rate the certainty of the evidence. We included 4 RCTs with 634 patients aged 68 to 81 years. Over a mean follow-up of 3 days to 34 months, acetazolamide significantly increased diuresis (MD 899.2 mL; 95% CI 249.5 to 1549; p < 0.01) and natriuresis (MD 72.44 mmol/L; 95% CI 39.4 to 105.4; p < 0.01) after 48 h of its administration. No association was found between acetazolamide use and WRF (RR 2.4; 95% CI 0.4 to 14.2; p = 0.3) or all-cause mortality (RR 1.2; 95% CI 0.8 to 1.9; p = 0.3). Clinical decongestion was significantly higher in the intervention group (RR 1.35; 95% CI 1.09 to 1.68; p = 0.01). Acetazolamide is an effective add-on therapy in patients with AHF, increasing diuresis, natriuresis, and clinical decongestion, but it was not associated with differences in mortality. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to investigate the effect of aqueous and methanolic extracts of Grewia flavescens (AEGF and MEGF respectively) on kidney stones using in vitro and in vivo methods. In vitro anti-urolithiasis activity was performed by different assays like nucleation, crystal growth, crystal aggregation, and crystal dissolution assays were performed and cell viability studies were performed on the MDCK cell line before and after exposure to oxalate. An HPTLC and HPLC method was developed for the quantification of diosgenin, catechin, rutin, gallic acid, and quercetin in extract. For an in vivo study, performed a diuretic activity model and sodium oxalate-induced urolithiasis in male Wistar albino rats. Determination of body and kidney weight, measurement of various biochemical parameters in biological samples, and examination of histology of the kidney at the end of the experiment were also done. AEGF and MEGF exhibited a concentration-dependent inhibitory activity on nucleation and aggregation along with a decreased number of calcium oxalate crystals produced in calcium oxalate metastable solutions in the in vitro experiments. Cell line study showed that extracts showed cell viability in the presence of oxalate. Co-administration of AEGF and MEGF with sodium oxalate has significantly (p

Daylily (Hemerocallis citrina) is a perennial herb of the genus Hemerocallis of Liliaceae. It is also an economically important crop and is widely cultivated. Daylily has nutritional, medicinal and ornamental values. The research literature shows that daylily is a high-quality food raw material rich in soluble sugars, ascorbic acid, flavonoids, dietary fiber, carotenoids, mineral elements, polyphenols and other nutrients, which are effective in clearing heat and diuresis, resolving bruises and stopping bleeding, strengthening the stomach and brain, and reducing serum cholesterol levels. This article reviews the main nutrients of daylily and summarizes the drying process of daylily. In addition, due to the existence of active ingredients, daylily also has a variety of biological activities that are beneficial to human health. This article also highlights the nutritional quality of daylily, the research progress of dried vegetable rehydration technology and dried daylily. In the end, the undeveloped molecular mechanism and functional research status of daylily worldwide are introduced in order to provide reference for the nutritional quality research and dried processing industry of daylily. [ABSTRACT FROM AUTHOR]

Introduction: Accurate volume status monitoring is crucial for effective diuretic therapy in patients with acute decompensated heart failure (ADHF). While guidelines recommend daily standing body weight measurement as an indicator of volume status, bed scales are commonly used in healthcare facilities. Methods: A method-comparison design was used to compare bed and standing scale weights among adults hospitalized with ADHF at Los Angeles County–University of Southern California Medical Center between March and April 2023. Results & Conclusion: Among 51 weight pairs from 43 participants, a clinically significant mean difference of 1.42 ± 1.18 kg was observed, exceeding the recommended threshold. Inaccuracies, with 71% showing differences >0.6 kg, highlight potential fluid management errors when relying on bed scales in ADHF hospitalizations. Article highlights Heart failure affects 6.5 million Americans, with acute decompensated heart failure causing over 1 million annual inpatient admissions with significant healthcare costs. Accurate weight measurement is essential in determining a patient's volume status and titrating diuresis, a mainstay of therapy, in order to reduce hospitalization duration and prevent readmission. Guidelines recommend daily monitoring of standing body weight, though many hospitals use bed scales instead. This study compared weights obtained via bed and standing scales among patients hospitalized with acute decompensated heart failure. Bed scale weights were inaccurate compared with standing scale weights, with a mean difference of 1.42 ± 1.18 kg (95% CI: -0.894 to 3.73), exceeding the recommended threshold. Factors contributing to inaccuracies include inadequate bed calibration and the presence of extra items during in-bed weighing. Inaccuracies in bed scale weights highlight the need for reform in this current standard practice of care in order to avoid potential errors in medical management, reduce readmission, and facilitate the self-monitoring of patients' weights at home. [ABSTRACT FROM AUTHOR]

Plantain (Plantago lanceolata L.) has recently been thrust into the limelight as a potential tool for mitigating nitrogen losses from the New Zealand pastoral environment. It is claimed to possess characteristics to reduce nitrogen leaching through both animal and soil-based mechanisms. This review examines the use of plantain in New Zealand pastures and the research that has led to these claims. The focus is on the evaluation of scientific evidence for the mechanisms through which plantain is proposed to reduce nitrate leaching, as well as the research on the implementation of plantain into pastoral farm systems. Plantain clearly increases the urination of grazing animals; a trait not unique to plantain. This review concludes that many research studies supporting the beneficial impact of plantain do not stand up against scientific scrutiny associated with methodology and interpretation of data. It is recommended more research should be undertaken on other pasture species and management tools, that may be more effective alternatives to plantain for nitrogen mitigation in pastures. [ABSTRACT FROM AUTHOR]

Introduction We tested the hypothesis that a carbohydrate (CHO: 6.5%) or carbohydrate–electrolyte (CHO + E: 6.5% + 50 mmol/L NaCl) drink would better recover plasma volume (PV) and exercise performance compared to water (H2O) after immersion diuresis. Methods Twelve men (24 ± 2 years; 82.4 ± 15.5 kg; and V̇O2max: 49.8 ± 5.1 mL · kg−1 · min−1) completed four experimental visits: a no-immersion control (CON) and three 4-h cold-water (18.0 °C) immersion trials (H2O, CHO, and CHO + E) followed by exercise in a warm environment (30 °C, 50% relative humidity). The exercise was a 60-minute loaded march (20.4 kg; 55% VO2max) followed by a 10-minute intermittent running protocol. After immersion, subjects were rehydrated with 100% of body mass loss from immersion diuresis during the ruck march. PV is reported as a percent change after immersion, after the ruck march, and after the intermittent running protocol. The intermittent running protocol distance provided an index of exercise performance. Data are reported as mean ± SD. Results After immersion, body mass loss was 2.3 ± 0.7%, 2.3 ± 0.5%, and 2.3 ± 0.6% for H2O, CHO, and CHO + E. PV loss after immersion was 19.8 ± 8.5% in H2O, 18.2 ± 7.0% in CHO, and 13.9 ± 9.3% in CHO + E, which was reduced after the ruck march to 14.7 ± 4.7% (P  = .13) in H2O, 8.8 ± 8.3% (P  < .01) in CHO, and 4.4 ± 10.9% (P  = .02) in CHO + E. The intermittent running protocol distance was 1.4 ± 0.1 km in CON, 1.4 ± 0.2 km in H2O, 1.4 ± 0.1 km in CHO, and 1.4 ± 0.2 km in CHO + E (P  = .28). Conclusions Although CHO and CHO + E better restored PV after immersion, post-immersion exercise performance was not augmented compared to H2O, highlighting that fluid replacement following immersion diuresis should focus on restoring volume lost rather than fluid constituents. [ABSTRACT FROM AUTHOR]

Understanding the function of the kappa opioid receptor (KOP) is crucial for the development of novel therapeutic interventions that target KOP for the treatment of pain, stress‐related disorders and other indications. Activation of KOP produces diuretic effects in rodents and man. Sex is a vital factor to consider when assessing drug response in pre‐clinical and clinical studies. In this study, the diuretic effect of the KOP agonist, U50488 (1–10 mg/kg), was investigated in both adult female and male Wistar rats that were either normally hydrated or water‐loaded. The KOP antagonist norbinaltorphimine (norBNI, 10 mg/kg) was administered 24 h prior to U50488 to confirm the involvement of KOP. U50488 elicited a significant diuretic response at doses ≥ 3 mg/kg in both female and male rats independent of hydration status. U50488 diuretic effects were inhibited by norBNI pre‐administration. Water‐loading reduced data variability for urine volume in males, but not in females, compared with normally hydrated rats. Sex differences were also evident in U50488 eliciting a significant increase in sodium and potassium ion excretion only in males. This may suggest different mechanisms of U50488 diuretic action in males where renal excretion mechanisms are directly affected more than in females. [ABSTRACT FROM AUTHOR]

Background: The first uninterrupted sleep period (FUSP, time up to the first episode of enuresis/nocturia after falling asleep) is a frequently investigated parameter in adults with nocturia, as it correlates with quality of life. However, it has not been included in pediatric enuresis studies. Aim: Investigate FUSP, circadian renal water and sodium handling, as well as sleep quality before and after desmopressin therapy in enuresis. Materials and Methods: We conducted a post hoc analysis of a prospective study in 30 treatment‐naïve children with enuresis who underwent a video‐polysomnography and a 24‐h urine concentration profile before and after 6 months of desmopressin therapy. We analyzed FUSP, periodic limb movements in sleep (PLMS), and arousal indexes and their correlations with the urinary parameters. Results: Sixteen children with a mean age of 10.9 ± 3.1 years had full registrations and were included in this subanalysis. After therapy, FUSP was significantly longer (p < 0.001), and the PLMS index was lower (p = 0.023). Significant differences in the circadian rhythm of diuresis (night/day diuresis, p = 0.041), nocturnal urinary osmolality (p = 0.009), and creatinine (p = 0.001) were found, demonstrating the increase of urinary concentration overnight by desmopressin, as well as a significant antidiuretic effect (diuresis [p = 0.013] and diuresis rate (p = 0.008). There was no correlation between the difference of FUSP, PLMS index, and urinary parameters. Nevertheless, despite this study being underpowered, there are indications of a correlation between nocturnal diuresis and diuresis rate. Results: Our results support the need for further research regarding FUSP in children with enuresis, in accordance with nocturia studies in adults, as this parameter could be valuable in the follow‐up and evaluation of therapeutic strategies for enuresis. [ABSTRACT FROM AUTHOR]

Introduction: This article delves into the intricate relationship between kidney function, diuresis, and lower urinary tract symptoms (LUTS) throughout the transitions of the human lifespan. It explores circadian regulation of urine production, maturation of renal function from birth to adulthood, and effects of aging on kidney function and LUTS. The complex connections between these factors are highlighted, offering insights into potential interventions and personalized management strategies. Methods: An international panel of seven experts engaged in online discussions, focusing on kidney function, diuresis, and LUTS throughout life. This manuscript summarizes expert insights, literature reviews, and findings presented during a webinar and subsequent discussions. Results: Renal function undergoes significant maturation from birth to adulthood, with changes in glomerular filtration rate, diuresis, and tubular function. A circadian rhythm in urine production is established during childhood. Adolescents and young adults can experience persistent enuresis due to lifestyle factors, comorbidities, and complex physiological changes. In older adults, age‐related alterations in kidney function disrupt the circadian rhythm of diuresis, contributing to nocturnal polyuria and LUTS. Conclusion: The interplay between kidney function, diuresis, and LUTS is crucial in understanding lifelong urinary health. Bridging the gap between pediatric and adult care is essential to address enuresis in adolescents and young adults effectively. For older adults, recognizing the impact of aging on renal function and fluid balance is vital in managing nocturia. This holistic approach provides a foundation for developing innovative interventions and personalized treatments to enhance quality of life for individuals with LUTS across all stages of life. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to investigate the effect of aqueous and methanolic extracts of Grewia flavescens (AEGF and MEGF respectively) on kidney stones using in vitro and in vivo methods. In vitro anti-urolithiasis activity was performed by different assays like nucleation, crystal growth, crystal aggregation, and crystal dissolution assays were performed and cell viability studies were performed on the MDCK cell line before and after exposure to oxalate. An HPTLC and HPLC method was developed for the quantification of diosgenin, catechin, rutin, gallic acid, and quercetin in extract. For an in vivo study, performed a diuretic activity model and sodium oxalate-induced urolithiasis in male Wistar albino rats. Determination of body and kidney weight, measurement of various biochemical parameters in biological samples, and examination of histology of the kidney at the end of the experiment were also done. AEGF and MEGF exhibited a concentration-dependent inhibitory activity on nucleation and aggregation along with a decreased number of calcium oxalate crystals produced in calcium oxalate metastable solutions in the in vitro experiments. Cell line study showed that extracts showed cell viability in the presence of oxalate. Co-administration of AEGF and MEGF with sodium oxalate has significantly (p<0.001) increased the urine volume and the level of calculus inhibitors and decreased the level of calculus promoters. HPTLC and HPLC data showed that extracts contain catechin, rutin, gallic acid, and quercetin. These results data indicate that AEGF and MEGF showed significant activity in urolithiasis which might be due to their diuretic, crystal formation inhibitory effects and their ability to increase the levels of inhibitors and decrease the level of promoters of urolithiasis due to the presence of active constituents in extracts. [ABSTRACT FROM AUTHOR]

The targeted activation or inhibition of specific cell populations using chemogenetics allows the precise dissection of cellular signaling and function. Designer receptors exclusively activated by designer drugs (DREADDs) is a chemogenetic platform initially developed by mutating human muscarinic receptors to be unresponsive to endogenous acetylcholine but exclusively activated by an “inert” designer drug. Compound 21 (C21) is a new and potent DREADD agonist; however, radioligand assays from a recent report indicated its ability to bind to endogenous G protein-coupled receptors (GPCRs), including muscarinic M1–3 receptors. Whether this binding causes off-target effects is unclear. Renal innervation is important for the regulation of renal function, and the advent of chemogenetic tools provides significant opportunities for the mechanistic understanding of renal innervation and function. GPCRs such as adrenergic and muscarinic receptors play a role in renal function; thus, a careful pharmacological characterization of C21 in renal function is a prerequisite for this approach. Unexpectedly, an infusion of 1.0 mg/kg C21 in anesthetized mice caused an ∼4-fold increase in urine output and correspondingly increased the glomerular filtration rate (GFR), suggesting a C21-mediated acute diuretic effect. This acute diuresis effect was further confirmed in awake mice using voiding spot assays. The exact molecular mechanism for C21-mediated diuresis is unclear; however, we demonstrated by in vitro myography that C21 can effectively inhibit bladder smooth muscle contraction by antagonizing M3 receptors at the micromolar level, causing increased voiding size in vivo. In summary, C21 functions as a GPCR antagonist and has significant dose-dependent off-target effects in the renal system.

Abstract Background Alpha2-adrenoceptor agonists (α2-agonists) are widely used in animals as sedatives and for pre-anaesthetic medication. Medetomidine has often been given subcutaneously (SC) to rats, although its absorption rate is slow and the individual variation in serum drug concentrations is high via this route. In addition, α2-agonists have various effects on metabolic and endocrine functions such as hypoinsulinaemia, hyperglycaemia and diuresis. Vatinoxan is a peripherally acting α2-adrenoceptor antagonist that, as a hydrophilic molecule, does not cross the blood-brain barrier in significant quantities and thus alleviates peripheral cardiovascular effects and adverse metabolic effects of α2-agonists. Aim of this study was to evaluate the effects of vatinoxan on sedation, blood glucose concentration, voiding and heart and respiratory rates and arterial oxygen saturation in rats sedated with subcutaneous medetomidine, midazolam and fentanyl. Results Onset of sedation and loss of righting reflex occurred significantly faster with vatinoxan [5.35 ± 1.08 (mean ± SD) versus 12.97 ± 6.18 min and 6.53 ± 2.18 versus 14.47 ± 7.28 min, respectively]. No significant differences were detected in heart and respiratory rates and arterial oxygen saturation between treatments. Blood glucose concentration (18.3 ± 3.6 versus 11.8 ± 1.2 mmol/L) and spontaneous urinary voiding [35.9 (15.1–41.6), range (median) versus 0.9 (0–8.0) mL /kg/min] were significantly higher without vatinoxan. Conclusions Acceleration of induction of sedation, alleviation of hyperglycaemia and prevention of profuse diuresis by vatinoxan may be beneficial when sedating rats for clinical and experimental purposes with subcutaneous medetomidine, midazolam and fentanyl.

Nardos Lema Wondimu,1,&ast; Mestayet Geta Mengistie,2,&ast; Jibril Seid Yesuf2,&ast; 1Department of Pharmacy, College of Medicine and Health Sciences, Wolkite University, Wolkite, Ethiopia; 2Department of Pharmacology, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia&ast;These authors contributed equally to this workCorrespondence: Nardos Lema Wondimu, Tel +251910540868, Email nardoslema123@gmail.comPurpose: To evaluate the diuretic effects of aqueous (AQ) and hydromethanolic crude extract (HM) the as well as the solvent fractions of the HM extract from Erica arborea flowers in mice.Methods: Mice were administered AQ and HM crude extracts, along with solvent fractions of HM extracts of E. arborea flowers, including HXF (n-hexane fraction), EAF (ethyl acetate fraction), and AQF (aqueous fraction), at doses ranging from 100 to 400 mg/kg orally. The effects of these extracts and solvent fractions on urine and salt excretion over 5 hours were compared to the effects of the solvent used for reconstitution and a standard drug (furosemide 10 mg/kg), as well as to each other.Results: The HM crude extract at a lower dose (100 mg/kg) significantly increased urine volume and salt excretion starting from the 3rd h compared to the AQ crude extract. Similar effects were observed for EAF. Notably, the HM extract and its EAF at 400 mg/kg showed comparable urine and salt excretion profiles to the standard drug.Conclusion: This study demonstrated that HM extract and EAF promote better diuresis, likely due to their saluretic properties. Furthermore, it confirms the diuretic activity of Erica arborea flowers.Keywords: diuresis, natriuresis, urine electrolyte, urine pH, mice

Nephrogenic diabetes insipidus is a heterogeneous disease in the etiopathogenesis of which are involved acquired and congenital factors. In this case, the kidneys do not respond to vasopressin and continue to produce large concentrated volumes of urine. Distinctive features in the pathology of central genesis are the fact of trauma, brain tumor with involvement of pituitary gland, response to intranasal vasopressin in the form of decreased diuresis.For diagnosis it is important to perform a series of differential diagnostic tests.In this article we present a unique clinical case of a patient with a long-term course of diabetes insipidus with the development a spectrum of comorbid conditions, metabolic disorders, required kidney transplantation.

Abstract Background This study evaluates the association of diuresis and hydration through a new monitoring indicator called $${U}_{sen}$$ U sen and the risk of acute kidney injury in patients treated with cisplatin based-EXTREME regimen. Methods We retrospectively reviewed all the cycles of patients with recurrent and/or metastatic head and neck cancer who received cisplatin based-EXTREME regimen from June 2008 to July 2022. Hydration regimen, urine output and concomitant treatments data were collected on the day of cisplatin infusion and the following day of each course received. Results Of the 110 courses received by 46 patients, 38 (34.5%) results in AKI. No patient characteristics showed a significant difference between AKI (70%) and non-AKI (30%) group. In univariate analysis, dose reduction of cisplatin (odds ratio = 0.166 [0.04; 0.75], p = 0.01)) and $${U}_{sen}$$ U sen >8 (odds ratio = 0.316 [0.133; 0.755], p = 0.015) and cardiac treatments (odds ratio = 3.24 [1.26; 8.52], p = 0.02) were significantly associated with AKI risk. In multivariate analysis, cisplatin dose reduction (odds ratio = 0.129 [0.0241; 0.687], p = 0.016) and $${U}_{sen}$$ U sen >8 (odds ratio = 0.184 [0.0648; 0.523], p = 0.0015) were associated with a risk reduction of cisplatin-related AKI. Concomitant administration of cardiac treatments (odds ratio = 3.18 [1.1; 9.22], p = 0.033) showed an increased risk of cisplatin-related AKI. Conclusion The combination of diuresis and i.v. hydration through the $${U}_{sen}$$ U sen composite score was shown to be associated with cisplatin-induced AKI risk in patients treated with cisplatin based EXTREME regimen. It could be used as a practical indicator to trigger specific clinical management to limit the risk of cisplatin induced AKI.

Background: Alpha2-adrenoceptor agonists (α2-agonists) are widely used in animals as sedatives and for pre-anaesthetic medication. Medetomidine has often been given subcutaneously (SC) to rats, although its absorption rate is slow and the individual variation in serum drug concentrations is high via this route. In addition, α2-agonists have various effects on metabolic and endocrine functions such as hypoinsulinaemia, hyperglycaemia and diuresis. Vatinoxan is a peripherally acting α2-adrenoceptor antagonist that, as a hydrophilic molecule, does not cross the blood-brain barrier in significant quantities and thus alleviates peripheral cardiovascular effects and adverse metabolic effects of α2-agonists. Aim of this study was to evaluate the effects of vatinoxan on sedation, blood glucose concentration, voiding and heart and respiratory rates and arterial oxygen saturation in rats sedated with subcutaneous medetomidine, midazolam and fentanyl. Results: Onset of sedation and loss of righting reflex occurred significantly faster with vatinoxan [5.35 ± 1.08 (mean ± SD) versus 12.97 ± 6.18 min and 6.53 ± 2.18 versus 14.47 ± 7.28 min, respectively]. No significant differences were detected in heart and respiratory rates and arterial oxygen saturation between treatments. Blood glucose concentration (18.3 ± 3.6 versus 11.8 ± 1.2 mmol/L) and spontaneous urinary voiding [35.9 (15.1–41.6), range (median) versus 0.9 (0–8.0) mL /kg/min] were significantly higher without vatinoxan. Conclusions: Acceleration of induction of sedation, alleviation of hyperglycaemia and prevention of profuse diuresis by vatinoxan may be beneficial when sedating rats for clinical and experimental purposes with subcutaneous medetomidine, midazolam and fentanyl. [ABSTRACT FROM AUTHOR]

The optimal diuretic doses of quercetin and rutin (5 mg/kg) and dihydroquercetin and hyperoside (1 mg/kg) were determined in experiments on white rats with a single intragastric administration. The mechanism of action of sodium quercetin and its derivatives on glomerular filtration and tubular transport was studied in acute experiments. Quercetin, dihydroquercetin, rutin, and hyperoside with a single intramuscular injection at the above doses contributed to an increase in diuresis, saluresis, creatinine clearance (except for rutin), and excreted sodium fraction by an average of 141%, 203%, 153%, and 189%, respectively (p < 0.05). Rutin also led to a decrease in the creatinine concentration index (by an average of 79%, p < 0.05). The diuretic furosemide with a single intramuscular injection at the threshold dose of 1 mg/kg increased diuresis, saluresis, and excreted sodium fraction (by an average of 187%, p < 0.05), like the effect of the quercetin derivatives; decreased the creatinine concentration index (by an average of 62%, p < 0.05); and did not affect creatinine clearance identically to the effect of rutin. [ABSTRACT FROM AUTHOR]

This article highlights a selection of important nephrology studies published in 2023 that have relevance for nonnephrologist physicians. Four studies examined progression of chronic kidney disease or cardiovascular disease with respect to finerenone use, magnesium supplementation, iron markers, and COVID-19. Two studies examined treatments to improve specific aspects of chronic kidney disease management, including daprodustat to address anemia and patiromer to address hyperphosphatemia. One study showed that acetazolamide added to loop diuretics increased diuresis in acute decompensated heart failure across a wide range of renal function. Another study found that once-daily hydrochlorothiazide did not prevent kidney stone recurrence. Finally, an antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infection in frail older adults. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor–naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51–4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98–3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77–12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: −9.1 mL/kg/d [95% CI: −14 to −4.12; P < 0.001]; late: −11.0 mL/kg/d [95% CI: −15.94 to −6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28–229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: −1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: −3.83 to 5.62]; P = 0.70). Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518). [Display omitted] [ABSTRACT FROM AUTHOR]

The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals. The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF. In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee. For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P = 0.06). Dapagliflozin was associated with reduced loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] vs 800 mg [Q1-Q3: 380-1,715 mg]; P = 0.006) and fewer intravenous diuretic up-titrations (P ≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P = 0.03) and urine output (P = 0.005), expediting hospital discharge over the study period. Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute Heart Failure [DICTATE-AHF]; NCT04298229) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: This study evaluates the association of diuresis and hydration through a new monitoring indicator called U sen and the risk of acute kidney injury in patients treated with cisplatin based-EXTREME regimen. Methods: We retrospectively reviewed all the cycles of patients with recurrent and/or metastatic head and neck cancer who received cisplatin based-EXTREME regimen from June 2008 to July 2022. Hydration regimen, urine output and concomitant treatments data were collected on the day of cisplatin infusion and the following day of each course received. Results: Of the 110 courses received by 46 patients, 38 (34.5%) results in AKI. No patient characteristics showed a significant difference between AKI (70%) and non-AKI (30%) group. In univariate analysis, dose reduction of cisplatin (odds ratio = 0.166 [0.04; 0.75], p = 0.01)) and U sen >8 (odds ratio = 0.316 [0.133; 0.755], p = 0.015) and cardiac treatments (odds ratio = 3.24 [1.26; 8.52], p = 0.02) were significantly associated with AKI risk. In multivariate analysis, cisplatin dose reduction (odds ratio = 0.129 [0.0241; 0.687], p = 0.016) and U sen >8 (odds ratio = 0.184 [0.0648; 0.523], p = 0.0015) were associated with a risk reduction of cisplatin-related AKI. Concomitant administration of cardiac treatments (odds ratio = 3.18 [1.1; 9.22], p = 0.033) showed an increased risk of cisplatin-related AKI. Conclusion: The combination of diuresis and i.v. hydration through the U sen composite score was shown to be associated with cisplatin-induced AKI risk in patients treated with cisplatin based EXTREME regimen. It could be used as a practical indicator to trigger specific clinical management to limit the risk of cisplatin induced AKI. [ABSTRACT FROM AUTHOR]

Although body fluid volume control by the kidneys may be classified as a long-term arterial pressure (AP) control system, it does not necessarily follow that the urine flow (UF) response to changes in AP is slow. We quantified the dynamic characteristics of the UF response to short-term AP changes by changing mean AP between 60 mmHg and 100 mmHg every 10 s according to a binary white noise sequence in anesthetized rats (n = 8 animals). In a baro-on trial (the carotid sinus baroreflex was enabled), the UF response represented the combined synergistic effects of pressure diuresis (PD) and neurally mediated antidiuresis (NMA). In a baro-fix trial (the carotid sinus pressure was fixed at 100 mmHg), the UF response mainly reflected the effect of PD. The UF step response was quantified using the sum of two exponential decay functions. The fast and slow components had time constants of 6.5 ± 3.6 s and 102 ± 85 s (means ± SD), respectively, in the baro-on trial. Although the gain of the fast component did not differ between the two trials (0.49 ± 0.21 vs. 0.66 ± 0.22 lL·min-1·kg-1·mmHg-1), the gain of the slow component was greater in the baro-on than in the baro-fix trial (0.51 ± 0.14 vs. 0.09 ± 0.39 lL·min-1·kg-1·mmHg-1, P = 0.023). The magnitude of NMA relative to PD was calculated to be 32.2 ± 29.8%. In conclusion, NMA contributed to the slow component, and its magnitude was approximately one-third of that of the effect of PD. [ABSTRACT FROM AUTHOR]

Aim: We examined the acute effects of a moderate alcohol dose (48 g) ingested before prolonged cycling on acute physiological responses in eight healthy males (mean ± SD; 23 ± 2 years; 1.77 ± 0.04 m; 75.8 ± 4.1 kg). Methods: In a randomized order, euhydrated participants completed two experimental sessions with the sequence of 150-min seated at rest, 90-min of cycling at 50% of the maximal rate of oxygen consumption (⁠|$\dot{\textrm V}\textrm O$| 2max), 120-min seated at rest. Participants drank 250 mL of flavored squash with or without alcohol (vodka; ~16 g) at 10, 40, and 70 min of the initial resting phase, giving a cumulative fluid intake of 750 mL with 48 g of alcohol. Heart rate, blood glucose, breath alcohol concentration, and respiratory gasses were recorded throughout the entire trial with cumulative urine volume recorded during both rest phases. Results: Total carbohydrate (control = 115 ± 19 g: alcohol = 119 ± 21 g; P  = 0.303) and lipid (control = 17 ± 4 g: alcohol = 20 ± 7 g; P  = 0.169) oxidation was similar between conditions. Average heart rate was 7% higher in the alcohol condition (control = 111 ± 12 bpm; alcohol = 119 ± 11 bpm; P  = 0.003). Blood glucose concentrations were similar between conditions during (P  = 0.782) and after exercise (P  = 0.247). Urine output was initially increased between conditions following alcohol ingestion before diminishing (P  < 0.001) with no difference in total cumulative urine output (P  = 0.331). Conclusion: Consuming an alcoholic drink containing 48 g of alcohol in the hour before moderate intensity sub-maximal aerobic exercise led to detectable increases in heart rate and rate of urine production with no effect on substrate use. [ABSTRACT FROM AUTHOR]

Constipation is one of the most common symptoms in childhood. Sodium-phosphate enemas are frequently preferred for the treatment of constipation and bowel cleansing. We present a case of a 5-year-old boy who presented to the Pediatric Emergency Department with complaints of constipation, abdominal pain, abdominal distension and vomiting; had been constipated for about two years and had poor nutrition, and received a full dose of CT enema® twice in the last 12 hours before admission to the hospital. Upon arrival at the Pediatric Emergency Department, the patient was given a pediatric fleet enema because he had dense stools according to radiographic evidence. Poisoning due to Sodium-phosphate enema was considered due to severe hyperphosphatemia and hypocalcemia in the laboratory evaluation. Rapid intravenous hydration and 1 mL/kg calcium gluconate intravenous infusion were started. Electrolytes returned to the normal range at the 14th hour of follow-up without the need for additional treatment. This case is presented to emphasize that due to the widespread use of sodium-phosphate enemas in the treatment of chronic constipation, these enemas can cause phosphate poisoning even when used in healthy patients at therapeutic doses. [ABSTRACT FROM AUTHOR]

High altitude is an independent risk factor for acute kidney injury （AKI）. In early stage, normal kidneys may modulate their functions and structures to adapt to a high plateau. Individuals progressing to AKI have a higher mortality. At the level of kidney, physiological adaptation to a high altitude has been poorly elucidated. Our understanding of kidney injury in a plateau environment is insufficient so that treatment strategy is not targeted. It may easily delay the disease and miss the best time for treatment. This review focused upon changes in renal blood flow, hypoxic renal diuretic effect, renal intrinsic cells and renal tubulointerstitial function of kidneys during a rapid altitude exposure and provided theoretical rationales for managing kidney injury in simulated high-altitude.

Abstract Background Poor natriuresis is a potential marker of diuretic resistance in dogs with acute congestive heart failure (CHF) but little is known about the relationship between urine sodium concentration (uNa) and frequency of successful decongestion. Supplemental O2 is a common treatment in dogs with severe CHF. The time from start to discontinuation of supplemental O2 therapy (DCSO2) typically reflects the time course and ease of decongestion. Hypothesis/Objectives Urine Na concentration after IV administration of furosemide will be correlated with duration of treatment with supplemental O2 (timeO2) and the cumulative frequency of successful DCSO2 during hospitalization. Animals Fifty‐one dogs with acute CHF. Methods Retrospective observational single center study. Results Dogs with low uNa had significantly longer mean timeO2 than dogs with high uNa (uNa

Adenine phosphoribosyltransferase (APRT) enzyme deficiency is a rare inborn metabolic error causing an accumulation of 2,8 dihydroxyadenine (DHA), leading to kidney stones and crystal nephropathy. If untreated, it progresses to end stage renal disease (ESRD) with a subsequent risk of crystal nephropathy recurrence post-renal transplantation. Recurrence post-transplant can be prevented, and allograft outcomes can be improved if treatment with an xanthine oxidoreductase (XOR) inhibitor is initiated before or at the time of kidney transplantation. We describe a case involving a 24-year-old male with ESRD, found to have APRT enzyme deficiency during transplant evaluation, successfully managed with pre- and post-transplant XOR inhibitors to prevent recurrence, resulting in a positive allograft outcome. [ABSTRACT FROM AUTHOR]

Background: Sugar alcohols, such as erythritol, are low-impact candidates for attractive toxic sugar baits (ATSB) to kill mosquitoes. To determine whether erythritol has a viable future in ATSB formulations, a suite of assays was conducted to diagnose toxicity mechanisms and starvation effects on mortality in Aedes aegypti (L.) as a model system. Methods: We measured general carbohydrate load, glucosidase levels, and free glucose in intoxicated adult mosquitoes to observe whether sugar digestion was impaired. We assayed the effects of sugar combinations with erythritol on larvae and adults. To measure erythritol effects when mosquitoes were not resource-deprived, additional assays manipulated the prior starvation status. Results: Up to 50,000 ppm of erythritol in water had no effect on larvae within 72 h, but an ammonia spike indicated diuresis in larvae as early as 4 h (F8,44 = 22.50, P < 0.0001) after sucrose/erythritol combinations were added. Adult consumption of erythritol was diuretic regardless of the sugar pairing, while sucrose and erythritol together generated above 80% mortality (F2,273 = 33.30, P < 0.0001) alongside triple the normal excretion (F5,78 = 26.80, P < 0.0004). Glucose and fructose paired individually with erythritol had less mortality, but still double the fecal excretion. When ingesting erythritol-laced meals, less sugar was detected in mosquitoes as compared to after sucrose meals (χ2 = 12.54, df = 1, P = 0.0004). Conclusions: Data showed that erythritol is a linear competitive inhibitor of α-glucosidase, marking it as a novel class of insecticide in the current research climate. However, the efficacy on larvae was null and not persistent in adult mosquitoes when compared across various starvation levels. Despite significant diuresis, the combined effects from erythritol are not acute enough for vector control programs considering ATSB against mosquitoes. [ABSTRACT FROM AUTHOR]

Simple Summary: The diagnosis of primary upper urinary tract urothelial carcinoma is challenging and may necessitate invasive procedures. In this study, through analysing two cohorts, we evaluated the diagnostic accuracy of drug-induced turbulence in the upper urinary tract and non-invasive urine sampling in the diagnosis of primary upper tract urothelial carcinoma and upper tract urothelial carcinoma recurrence during follow-up after radical cystectomy for primary bladder cancer. As a diagnostic tool, cytology of pharmacologically forced diuresis performs better in patients with invasive upper tract urothelial carcinoma and concomitant carcinoma in situ. As a method of surveillance, positive cytology of pharmacologically forced diuresis was related to cancer recurrence and could even detect recurrence in the urethra in cases involving an orthotopic bladder substitute. In conclusion, urine cytology in pharmacologically forced diuresis may be useful in patients with suspected upper tract urothelial carcinoma, especially in cases with contraindications for imaging or when achieving endoscopic access to the upper urinary tract is difficult. We performed a urine cytology analysis of a pharmacologically induced diuresis for the diagnosis of upper tract urothelial carcinoma. To evaluate the diagnostic value of cytology of pharmacologically forced diuresis, an initial cohort of 77 consecutive patients with primary upper tract urothelial carcinoma treated via radical surgery was enrolled. To evaluate pharmacologically forced diuresis cytology as a follow-up procedure, a second cohort of 1250 patients who underwent a radical cystectomy for bladder cancer was selected. In the first cohort, the sensitivity of cytology of pharmacologically forced diuresis in patients with invasive, high-grade, low-grade, and concomitant carcinoma in situ was 8%, 9%, 0%, and 14%, respectively. In the second cohort, cytology of pharmacologically forced diuresis was positive in 30/689 (4.3%) patients, in whom upper urinary tract recurrence was present in 21/30 (70%) of cases, and urethral recurrence was present in 8/30 (26%) of cases. As a follow-up tool, cytology of pharmacologically forced diuresis showed a sensitivity, specificity, and positive and negative predictive values of 60%, 99%, 70%, and 98%, respectively. Overall, as a diagnostic tool, the sensitivity of cytology of pharmacologically forced diuresis is slightly better in patients with invasive upper tract urothelial carcinoma and concomitant carcinoma in situ. As a follow-up method, positive cytology of pharmacologically forced diuresis is strongly related to cancer recurrence and can reveal urethral recurrence. Cytology of pharmacologically forced diuresis might be useful in cases with contraindications for imaging or when achieving endoscopic access to the upper urinary tract is difficult. [ABSTRACT FROM AUTHOR]

Background: The management of posterior urethral valve (PUV) in neonates requires close monitoring in the intensive care unit because of the risk of post-obstructive diuresis (POD). Our aim was to describe the incidence and factors associated with POD in newborns treated for PUV. Methods: Retrospective analysis of the medical records of all neonates who underwent surgical intervention for PUV in our neonatal intensive care unit between January 2014 and April 2021. Results: Of the 40 patients included, 15 (37.5%) had POD defined by urine output > 6 ml.kg−1.h−1 during the first 24 h following urinary tract obstruction relief. At prenatal ultrasound examinations, oligohydramnios was more common in the group with POD than in the group without (53.3% vs. 8%, p = 0.002). Preterm birth was more frequent in neonates with POD (66.7% vs. 8%; p < 0.001). Median serum creatinine (212 [137–246] vs. 95 [77–125] µmol.l−1; p < 0.001) and urea (8.5 [5.2–12.2] vs. 4.1 [3.5–4.7] mmol.l−1; p < 0.001) concentrations on the day of obstruction relief were significantly higher in the group with POD than in the group without. After adjustment for prematurity, logistic regression models confirmed correlation between the occurrence of POD and the severity of the consequences of urethral obstruction (i.e., oligohydramnios and serum creatinine levels; ß = 2.90 [0.88; 5.36], p = 0.013 and ß = 0.014 [0.003; 0.031], p = 0.034, respectively). Conclusions: In neonates, POD is common after the relief of PUV-related obstruction. Our findings may help to identify patients at highest risk. [ABSTRACT FROM AUTHOR]

The urine concentration impairment responsible for hyposthenuria in sickle cell nephropathy is currently thought to be a consequence of renal medulla lesions, which lead to nephrogenic diabetes insipidus. The objective of the present study was to investigate the mechanism of hyposthenuria in patients with sickle cell anemia. We performed an observational study of patients with homozygous SS sickle cell anemia and data available on the fasting plasma antidiuretic hormone (ADH) concentration. A total of 55 patients were analyzed. The fasting plasma ADH values ranged from 1.2 to 15.4 pg/mL, and 82% of the patients had elevated ADH values and low fasting urine osmolality (<505 mosmol/kgH2O). Plasma ADH was positively associated with plasma tonicity and natremia (P < 0.001). None of the patients experienced polyuria and fasting free water clearance was negative in all cases, thus, ruling out nephrogenic diabetes insipidus. The tertile groups did not differ with regard to fasting urine osmolality, plasma renin level, mGFR, or several hemolysis biomarkers. The negative fasting free water clearance in all cases and the strong association between 24-h osmolal clearance and 24-h diuresis favors the diagnosis of osmotic diuresis due to an impaired medullary gradient, rather than lesions to collecting tubule. NEW & NOTEWORTHY The urine concentration impairment in sickle cell anemia is an osmotic diuresis related to an impaired renal medullary gradient leading to an ADH plateau effect. The fasting plasma ADH was high in the context of a basic state of close-to-maximal urine concentration probably driven by short nephrons maintaining a cortex-outer medullary gradient (about 400 milliosmoles). The patients had a low daily osmoles intake without evidence of thirst dysregulation so no one experienced polyuria. [ABSTRACT FROM AUTHOR]

Objectives: The diuretic and kidney protective effect of the 3-demethyl-2-geranyl-4-prenylbellidifoline (DGP) were evaluated in rats. Methods: The normotensive (NTR) and spontaneously hypertensive rats (SHR) received, once a day for 7 days, oral treatment with DGP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (10 ml/kg). Urine, blood, and kidney samples were collected for further analysis. Key findings: The urine and Na+ elimination content were significantly higher in the groups that received DGP. Furthermore, a Ca2+-sparing action was detected in the urine of DGP-treated groups, which was consistent with the reduction in calcium oxalate crystal formation. Relevantly, the treatment did not change the parameters examined in the blood. Concerning the renal analyses, DGP treatment recovered the morphological damages of the kidney corpuscle area of SHR. In addition to the differences observed between the NTR and SHR vehicle groups, DGP augmented the amount of reduced glutathione and the activity of glutathione S-transferase GST while reducing the catalase and N-acetyl-β-D-glucosaminidase activity and nitrite levels. Conclusion: Together, this study displayed the prolonged diuretic action of DGP and its natriuretic, Ca2+-sparing, and antiurolytic effects. The antioxidative and anti-inflammatory effects of DGP were evidenced in SHR kidneys, opening perspectives for further studies regarding the benefits of this xanthone. Graphical Abstract [ABSTRACT FROM AUTHOR]

Background: Poor natriuresis is a potential marker of diuretic resistance in dogs with acute congestive heart failure (CHF) but little is known about the relationship between urine sodium concentration (uNa) and frequency of successful decongestion. Supplemental O2 is a common treatment in dogs with severe CHF. The time from start to discontinuation of supplemental O2 therapy (DCSO2) typically reflects the time course and ease of decongestion. Hypothesis/Objectives: Urine Na concentration after IV administration of furosemide will be correlated with duration of treatment with supplemental O2 (timeO2) and the cumulative frequency of successful DCSO2 during hospitalization. Animals: Fifty‐one dogs with acute CHF. Methods: Retrospective observational single center study. Results: Dogs with low uNa had significantly longer mean timeO2 than dogs with high uNa (uNa <87 mmol/L, 24.2 ± 2.6 hours vs uNa ≥87 mmol/L, 16.6 ± 1.7 hours; P =.02). Low uNa was correlated with lower cumulative frequency of DCSO2 (12 hour, 28%; 24 hour, 42%; 36 hour, 73%) compared to high uNa (12 hour, 28%; 24 hour, 88%; 36 hour, 96%; P =.005). History of PO loop diuretics, low serum chloride concentration (sCl), and high PCV were associated with low uNa. Urine Na concentration outperformed other metrics of diuretic responsiveness including weight loss. Conclusions and Clinical Importance: Urine Na concentration after IV furosemide predicted timeO2 and cumulative frequency of DCSO2 in dogs with acute CHF, which likely reflects important aspects of diuretic responsiveness. Urine Na can assess diuretic responsiveness and treatment efficacy in dogs with CHF. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) patients often experience persistent fluid overload despite standard diuretic therapy. The adjunctive use of acetazolamide, a carbonic anhydrase inhibitor, in combination with loop diuretics has shown promise in improving decongestion and diuretic efficacy. This literature review aims to analyze six studies evaluating the effectiveness of acetazolamide as an additive treatment for acute decompensated heart failure (ADHF) and its impact on various outcomes. Methods: We searched the PubMed database using the terms "acetazolamide heart failure". We refined our search with specific filters (as shown our PRISMA flow diagram) and exclusion criteria, narrowing down our results to five studies. We included an extra study via expert recommendation, ultimately including six studies for comprehensive analysis. Results: The review highlights the positive effects of acetazolamide on decongestion, natriuresis, and diuresis in HF patients. However, it also showcases the limitations of these trials. Discussion: While the reviewed studies demonstrate the potential benefits of acetazolamide in enhancing decongestion and diuretic efficiency, there are limitations to consider, including small sample sizes, lack of blinding, and limited external validity. Further research is needed to confirm these findings, compare acetazolamide with other diuretic combinations, and explore its effects in a broader population of heart failure patients, including those in the United States. The use of acetazolamide in HF management warrants continued investigation to optimize its role in improving decongestion and patient outcomes. [ABSTRACT FROM AUTHOR]

The renal collecting duct is continuously exposed to a wide spectrum of fluid flow rates and osmotic gradients. Expression of a mechanoactivated Piezo1 channel is the most prominent in the collecting duct. However, the status and regulation of Piezo1 in functionally distinct principal and intercalated cells (PCs and ICs) of the collecting duct remain to be determined. We used pharmacological Piezo1 activation to quantify Piezo1-mediated [Ca2+]i influx and single-channel activity separately in PCs and ICs of freshly isolated collecting ducts with fluorescence imaging and electrophysiological tools. We also employed a variety of systemic treatments to examine their consequences on Piezo1 function in PCs and ICs. Piezo1 selective agonists, Yoda-1 or Jedi-2, induced a significantly greater Ca2+ influx in PCs than in ICs. Using patch clamp analysis, we recorded a Yoda-1-activated nonselective channel with 18.6 ± 0.7 pS conductance on both apical and basolateral membranes. Piezo1 activity in PCs but not ICs was stimulated by short-term diuresis (injections of furosemide) and reduced by antidiuresis (water restriction for 24 h). However, prolonged stimulation of flow by high K+ diet decreased Yoda-1-dependent Ca2+ influx without changes in Piezo1 levels. Water supplementation with NH4Cl to induce metabolic acidosis stimulated Piezo1 activity in ICs but not in PCs. Overall, our results demonstrate functional Piezo1 expression in collecting duct PCs (more) and ICs (less) on both apical and basolateral sides. We also show that acute changes in fluid flow regulate Piezo1-mediated [Ca2+]i influx in PCs, whereas channel activity in ICs responds to systemic acid-base stimuli. [ABSTRACT FROM AUTHOR]

Like other insects, secretion by mosquito Malpighian tubules (MTs) is driven by the V-type H+-ATPase (VA) localized in the apical membrane of principal cells. In Aedes aegypti, the antidiuretic neurohormone CAPA inhibits secretion by MTs stimulated by select diuretic hormones; however, the cellular effectors of this inhibitory signaling cascade remain unclear. Herein, we demonstrate that the VA inhibitor bafilomycin selectively inhibits serotonin (5HT)- and calcitonin-related diuretic hormone (DH31)-stimulated secretion. VA activity increases in DH31-treated MTs, whereas CAPA abolishes this increase through a NOS/cGMP/PKG signaling pathway. A critical feature of VA activation involves the reversible association of the cytosolic (V1) and membrane (Vo) complexes. Indeed, higher V1 protein abundance was found in membrane fractions of DH31-treated MTs, whereas CAPA significantly decreased V1 abundance in membrane fractions while increasing it in cytosolic fractions. V1 immunolocalization was observed strictly in the apical membrane of DH31-treated MTs, whereas immunoreactivity was dispersed following CAPA treatment. VA complexes colocalized apically in female MTs shortly after a blood meal consistent with the peak and postpeak phases of diuresis. Comparatively, V1 immunoreactivity in MTs was more dispersed and did not colocalize with the Vo complex in the apical membrane at 3 h post blood meal, representing a time point after the late phase of diuresis has concluded. Therefore, CAPA inhibition of MTs involves reducing VA activity and promotes complex dissociation hindering secretion. Collectively, these findings reveal a key target in hormone-mediated inhibition of MTs countering diuresis that provides a deeper understanding of this critical physiological process necessary for hydromineral balance. [ABSTRACT FROM AUTHOR]

Purpose: Maintaining an appropriate hydration level by ingesting fluid in a hot environment is a measure to prevent heat-related illness. Caffeine-containing beverages, including green tea (GT), have been avoided as inappropriate rehydration beverages to prevent heat-related illness because caffeine has been assumed to exert diuretic/natriuretic action. However, the influence of caffeine intake on urine output in dehydrated individuals is not well documented. The aim of the present study was to examine the effect of fluid replacement with GT on body fluid balance and renal water and electrolyte handling in mildly dehydrated individuals. Methods: Subjects were dehydrated by performing three bouts of stepping exercise for 20 min separated by 10 min of rest. They were asked to ingest an amount of water (H2O), GT, or caffeinated H2O (20 mg/100 ml; Caf-H2O) that was equal to the volume of fluid loss during the dehydration protocol; fluid balance was measured for 2 h after fluid ingestion. Results: The dehydration protocol induced hypohydration by ~ 10 g/kg body weight (~ 1% of body weight). Fluid balance 2 h after fluid ingestion was significantly less negative in all trials, and the fluid retention ratio was 52.2 ± 4.2% with H2O, 51.0 ± 5.0% with GT, and 47.9 ± 6.2% with Caf-H2O; those values did not differ among the trials. After rehydration, urine output, urine osmolality, and urinary excretions of osmotically active substances, sodium, potassium and chloride were not different among the trials. Conclusion: The data indicate that ingestion of GT or an equivalent caffeine amount does not worsen the hydration level 2 h after ingestion and can be effective in reducing the negative fluid balance for acute recovery from mild hypohydration. Trial registration: ISRCTN53057185; retrospectively registered. [ABSTRACT FROM AUTHOR]

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a protein kinase that inactivates eEF2, a protein that mediates a peptidyl-tRNA translocation during an elongation step of protein synthesis. We have previously shown that eEF2K was involved in pathogenesis of essential and pulmonary hypertension. A484954 (7-amino-1-cyclopropyl-3-ethyl-2,4-dioxo-1,2,3,4- tetrahydropyrido[2,3-d] pyrimidine-6-carboxamide), a selective eEF2K inhibitor, is a membrane permeable small molecule. We have previously shown that A484954 lowered blood pressure and induced diuretic effects in spontaneously hypertensive rats (SHR) due to an increase in renal blood flow. Here we aimed to reveal mechanisms underlying the diuretic effects of A484954 in SHR. A484954-induced diuresis and increase in urinary Na+ excretion were inhibited by N (G)-nitro-Larginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor. A484954 increased mRNA expression of angiotensin type 2 receptor (AT2R) and nuclear factor-erythroid 2-related factor 2 (Nrf2). In summary, we for the first time revealed that A484954 induces diuresis in SHR at least partly via the activation of NO/Nrf2/AT2R pathway. [ABSTRACT FROM AUTHOR]

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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. Plain Language Summary: Continuous monitoring of urinary output in intensive care patients provides vital insights, potentially revealing low cardiac output, renal hypoperfusion, or deteriorating renal function. Currently, these measurements are done manually, prompting a need for automated, real-time monitoring using Internet of Medical Things (IoMT) devices. Current automatic urinometers are not widely used due to high costs, maintenance requirements, and logistical complications. However, we propose developing an affordable, updated urinometer that meets clinician needs and can be widely used in hospitals.This innovation would enable early intervention strategies to reverse or improve renal perfusion and prevent potential toxic treatments. The shift from manual to automated monitoring is likely, facilitating real-time data integration such as blood pressure, heart rate, and temperature. This can lead to personalized medical approaches and predictive algorithms for renal function deterioration.As technology, IoMT, big data, and artificial intelligence (AI) evolve, these advancements will be indispensable for hospital medicine, supporting precision medicine and efficient clinical operation. While we cannot predict the definitive method for continuous diuresis measurement, we anticipate the adoption of these technologies in the near future, improving diagnostics and clinical practice. If successful, the application could extend beyond critical care into postoperative or home care, not only for diuresis but for any fluid flow, enabling early pathology identification and potentially revealing diagnostic patterns through AI. [ABSTRACT FROM AUTHOR]