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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: 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]

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]

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]

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]

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]

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]

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]

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]

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]

Abstract Background Treatment with phenylbutazone (nonselective COX inhibitor) decreases the diuretic and natriuretic effects of furosemide by nearly 30% but the effects of COX‐2 specific inhibitors (firocoxib) and atypical NSAIDs (dipyrone) are unknown. Hypothesis Furosemide‐induced diuresis after pretreatment with firocoxib or dipyrone is diminished to a lesser extent than after pretreatment with phenylbutazone. Animals Eight healthy mares. Methods Each mare received 4 treatments in a prospective experimental crossover study using a replicated 4 × 4 Latin Square design: furosemide alone (FU), furosemide and phenylbutazone (PB), furosemide and firocoxib (FX), and furosemide and dipyrone (DP). After 24 hours of NSAID treatment at recommended dosages, ureteral catheters were placed for continual urine collection. After a 30‐minute baseline collection period, furosemide (1.0 mg/kg, IV) was administered, and urine and blood samples were collected for 4 hours. Data were assessed by repeated measures ANOVA. Results Four‐hour urine volume was (mean ± SD) ~25% less (P

BACKGROUND: Animal models implicate FGF-23 (fibroblast growth factor-23) as a direct contributor to adverse cardiorenal interactions such as sodium avidity, diuretic resistance, and neurohormonal activation, but this has not been conclusively demonstrated in humans. Therefore, we aimed to evaluate whether FGF-23 is associated with parameters of cardiorenal dysfunction in humans with heart failure, independent of confounding factors. METHODS: One hundred ninety-nine outpatients with heart failure undergoing diuretic treatment at the Yale Transitional Care Center were enrolled and underwent blood collection, and urine sampling before and after diuretics. RESULTS: FGF-23 was associated with several metrics of disease severity such as higher home loop diuretic dose and NT-proBNP (N-terminal pro-B-type natriuretic peptide), and lower estimated glomerular filtration rate, serum chloride, and serum albumin. Multivariable analysis demonstrated no statistically significant association between FGF-23 and sodium avidity measured by fractional excretion of sodium, or proximal or distal tubular sodium reabsorption, either before diuretic administration or at peak diuresis (P≥0.11 for all). Likewise, FGF-23 was not independently associated with parameters of diuretic resistance (diuretic excretion, cumulative urine and sodium output, and loop diuretic efficiency [P≥0.33 for all]) or neurohormonal activation (plasma or urine renin [P≥0.36 for all]). Moreover, the upper boundary of the 95% CI of all the partial correlations were ≤0.30, supporting the lack of meaningful correlations. FGF-23 was not associated with mortality in multivariable analysis (P=0.44). CONCLUSIONS: FGF-23 was not meaningfully associated with any cardiorenal parameter in patients with heart failure. While our methods cannot rule out a small effect, FGF-23 is unlikely to be a primary driver of cardiorenal interactions.

Introduction The risk of unfavourable outcomes after an acute heart failure (AHF) episode remains high. Effective decongestion, reflected by haemoconcentration (HC), may guide therapy. Optimal timing of HC remains unspecified. Methods We analysed the AHF registry to evaluate the prognostic differences of various timing of HC. Subjects were divided into 3 groups by time of reaching HC. Results The groups differed in terms of 1-year occurrence of a composite of the mortality and AHF hospitalization (26% vs. 46% vs. 40%, early vs. late vs. no HC, p = 0.016). Conclusions Patients reaching HC earlier seem to present the best prognosis regarding the analysed composite endpoint.

IntroductionAngiotensin receptor-neprilysin inhibitor (ARNi), comprised of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has established itself as a safe and effective intervention for hypertension. S086 is a novel ARNi cocrystal developed by Salubris for the treatment of heart failure and hypertension.MethodsDahl Salt Sensitive (DSS) hypertensive rat model and telemetry system were employed in this study to investigate the anti-hypertensive efficacy of S086 and compare it with the first ARNi-LCZ696.Results and discussionThe study showed that oral administration of S086 dose-dependently lowered blood pressure (P < 0.001). The middle dosage of S086 (23 mg/kg) exhibited efficacy comparable to LCZ696 (68 mg/kg), while also demonstrating superiority at specific time points (P < 0.05). Notably, water consumption slightly decreased post-treatment compared to the vehicle group. Furthermore, there were significant increases in natriuresis and diuresis observed on the first day of treatment with 23 mg/kg and 68 mg/kg S086 (P < 0.001). However, over the course of treatment, the effects in all treatment groups gradually diminished. This study demonstrates the anti-hypertensive efficacy of S086 in DSS hypertensive rat model, offering promising avenues for the clinical development of S086 as a hypertension treatment.

In patients with right heart failure (RHF) and pulmonary hypertension (PH), classical teaching often advises cautious diuresis in the setting of 'preload dependence' to avoid renal injury and hemodynamic compromise. However, while this physiology may hold true in some clinical settings, such as acute ischemia with right ventricular infarction, it cannot necessarily be extended to PH-related RHF. Rather, in patients with precapillary PH and decompensated RHF, diuresis aimed to decongest the right heart and systemic venous system may be directly beneficial. This study aimed to evaluate the effects of diuresis on renal function and blood pressure in patients with severe precapillary PH. A retrospective chart review was conducted on 62 patients with severe precapillary PH admitted for decompensated RHF. The hemodynamic phenotype of these patients was characterized by invasive hemodynamics and echocardiographic data. Laboratory and hemodynamic data were collected at both admission and discharge. After large-volume diuresis in this patient population, there was an improvement in both glomerular filtration rate and creatinine. While there was a decline in blood pressure after diuresis, this was not clinically significant, given the blood pressure remained in a normal range with improvement in renal function. In conclusion, this study demonstrated that despite concern for preload dependence, significant diuresis in patients with acute decompensated RHF from precapillary PH is not only safe but beneficial. [ABSTRACT FROM AUTHOR]

Background: Treatment with phenylbutazone (nonselective COX inhibitor) decreases the diuretic and natriuretic effects of furosemide by nearly 30% but the effects of COX‐2 specific inhibitors (firocoxib) and atypical NSAIDs (dipyrone) are unknown. Hypothesis: Furosemide‐induced diuresis after pretreatment with firocoxib or dipyrone is diminished to a lesser extent than after pretreatment with phenylbutazone. Animals: Eight healthy mares. Methods: Each mare received 4 treatments in a prospective experimental crossover study using a replicated 4 × 4 Latin Square design: furosemide alone (FU), furosemide and phenylbutazone (PB), furosemide and firocoxib (FX), and furosemide and dipyrone (DP). After 24 hours of NSAID treatment at recommended dosages, ureteral catheters were placed for continual urine collection. After a 30‐minute baseline collection period, furosemide (1.0 mg/kg, IV) was administered, and urine and blood samples were collected for 4 hours. Data were assessed by repeated measures ANOVA. Results: Four‐hour urine volume was (mean ± SD) ~25% less (P <.001) after pretreatment with all NSAIDs (PB 19.1 ± 2.1 mL/kg, FX 17.7 ± 3.5 mL/kg, DP 19.1 ± 3.9 mL/kg), as compared to FU (23.4 ± 5.1 mL/kg) (P <.001), but there were no differences between PB, FX, or DP. Interindividual variability in furosemide diuresis after pretreatment with different NSAIDs was observed. Conclusions and Clinical Importance: Though COX‐2 selective NSAIDs and dipyrone might have less severe or fever gastrointestinal adverse effects in horses, our data suggest minimal differences in effects on furosemide‐induced diuresis, and possibly, risk of nephrotoxicosis. [ABSTRACT FROM AUTHOR]

Background: Right living donor nephrectomy is technically more demanding because of the anatomical differences. Patient safety is the utmost priority because it is performed on healthy donors. We hereby describe our experiences with surgical modifications to minimize donor morbidity and overcome surgical challenges in the cases of right living donor nephrectomy. Materials and Methods: In this retrospective comparative study, we analyzed the prospectively maintained perioperative and follow-up data of standard and modified right living donor nephrectomies performed in the recent past 10 years at our institute. We also compared the significant events in corresponding recipients. Student's t-tests were used to define statistical significance. Results: A total of 1530 laparoscopic living donor nephrectomies were performed between 2012 and 2021, of which 117 were on the right side. Of them, 62 donors underwent modified right laparoscopic donor nephrectomy (MRLDN) and 55 underwent standard right laparoscopic donor nephrectomy. The mean duration of surgery (103.44 ± 14.59 vs. 139.45 ± 25.99 min), warm ischemia time (4.30 ± 0.59 vs. 5.89 ± 0.91 min), and blood loss (90.24 ± 24.75 vs. 103.72 ± 33.37 mL) were significantly lower in modified as compared to standard donor nephrectomy (P < 0.05). There was no significant difference in postoperative diuresis, acute tubular necrosis, and serum creatinine at 3 months in the corresponding recipient group. Conclusion: MRLDN is a safe, reliable, and reproducible technique of right laparoscopic donor nephrectomy. [ABSTRACT FROM AUTHOR]

Introduction Inversion of the patient, forced diuresis after hydration, and mechanical percussion technique was developed for lower renal pole (LRP) stones with extracorporeal shock wave (ESWL). In this study, we aimed to analyze the effect of percussion, diuresis and inversion (PDI) therapy on the success rates of retrograde intrarenal surgery (RIRS) for the LRP stones. Material and methods 114 patients who underwent RIRS for LRP stones <2cm were included in this study. Patients' demographic, clinical, radiological and anatomical features and success status were recorded prospectively. The patients were divided into two groups. One group received RIRS procedure only (non-PDI group) and the other group received PDI therapy after the RIRS procedure (PDI group). Results PDI was performed to 60 (52.6%) patients, and not performed to 54 (47.4%) patients. The success rate (58.3%) for the PDI group was higher than the non-PDI group (25.9%), and this difference was statistically significant (p <0.001). In multivariate logistic regression analysis, stone size (OR = 1.306; 95% CI = 1.019-1.674; p <0.001), IU (OR = 1.702; 95% CI = 1.383-2.096; p <0.001) and not performing PDI therapy (p <0.001) OR = 9.455; 95% Cl = 2.426-10.853; p = 0.001) were revealed to be independent risk factors for failure. Conclusions PDI therapy increases the success rates of RIRS performed for the LRP stones. [ABSTRACT FROM AUTHOR]

Congestion is a key pathophysiological feature of heart failure (HF) syndrome that drives most of the clinical manifestations of acute HF and is related with poor quality of life and outcomes. Therefore, safe and effective decongestion is an important therapeutic target in the management of acute HF and despite the use of guideline‐recommended loop diuretics, adequate decongestion is not always achieved in patients with acute HF. Recently, sodium–glucose cotransporter‐2 (SGLT‐2) inhibitors have been shown to provide clinical benefits across a broad spectrum of patients with HF, including consistent reduction in the risk of acute HF episodes. While the exact mechanisms underlying these benefits remain a matter of debate, a growing body of evidence suggests that effective decongestion may be partly responsible, especially in the setting of acute HF. In this review, we discuss the potential decongestive mechanisms of SGLT‐2 inhibitors, such as osmotic diuresis, natriuresis, preservation of glomerular filtration and facilitation of interstitial drainage, which can collectively translate into effective and safe decongestion. Furthermore, we provide a comprehensive review of up‐to‐date clinical data of SGLT‐2 inhibitor use in the acute HF population. [ABSTRACT FROM AUTHOR]

Introduction: The risk of unfavourable outcomes after an acute heart failure (AHF) episode remains high. Effective decongestion, reflected by haemoconcentration (HC), may guide therapy. Optimal timing of HC remains unspecified. Methods: We analysed the AHF registry to evaluate the prognostic differences of various timing of HC. Subjects were divided into 3 groups by time of reaching HC. Results: The groups differed in terms of 1-year occurrence of a composite of the mortality and AHF hospitalization (26% vs. 46% vs. 40%, early vs. late vs. no HC, p = 0.016). Conclusions: Patients reaching HC earlier seem to present the best prognosis regarding the analysed composite endpoint. [ABSTRACT FROM AUTHOR]

This single centre case series describes the presentation and management of six cases of peripartum hyponatraemia in women who were otherwise deemed low-risk at delivery. It highlights presenting symptoms such as fatigue, confusion and seizures as well as the effects on the neonate. It also focuses on areas of interest such as fluid intake, hormonal effects of ADH and oxytocin and the association with birthing pools for future research. [ABSTRACT FROM AUTHOR]

Arterial thrombosis occurs in <1% of kidney transplant patients. Most cases arise early in the postoperative period following technical problems. However, it can be delayed until after the 1st week. In contrast to total graft thrombosis, segmental thrombosis is uncommonly recognized. Although some reports suggest acute rejection as the cause of graft thrombosis, segmental thrombosis with infarction secondary to rejection has not been reported. Here, we present a case of donor-specific antibody-negative antibody-mediated rejection associated with segmental thrombosis and infarction. [ABSTRACT FROM AUTHOR]

We present an extremely rare case of renal ptosis from the normal orthotopic position into the cavity of inguinal hernia in a 93-year-old male patient. The following clinical case was accompanied by renal insufficiency, which was associated with the obstruction of the right ureter in the hernial sac and the stenosis of the left renal artery. The differential diagnosis between nephroptosis and dystopic kidney was based on MDCT scan images, which demonstrated the length of the right renal artery to be more than 20 cm. The patient underwent percutaneous nephrostomy through the right inguinal area and was successfully followed up for two years. We also analyzed six similar clinical cases described in the literature. This disease has, thus far, been observed exclusively in elderly men with long-standing and large inguinal hernias. The most frequent complications in these patients include ureteral strangulation in the area of the hernial gate and renal failure. [ABSTRACT FROM AUTHOR]

The intestinal peptide hormones guanylin (GN) and uroguanylin (UGN) interact with the epithelial cell receptor guanylate cyclase C to regulate fluid homeostasis. Some enterotoxigenic Escherichia coli (ETEC) produce heat-stable enterotoxin (ST), which induces diarrhea by mimicking GN and UGN. Plasma concentrations of prohormones of GN (proGN) and UGN (proUGN) are reportedly decreased during chronic diarrheal diseases. Here we investigate whether prohormone concentrations also drop during acute diarrhea caused by ST-producing ETEC strains TW10722 and TW11681. Twenty-one volunteers were experimentally infected with ETEC. Blood (n = 21) and urine (n = 9) specimens were obtained immediately before and 1, 2, 3, and 7 days after ETEC ingestion. Concentrations of proGN and proUGN were measured by ELISA. Urine electrolyte concentrations were measured by photometry and mass spectrometry. Ten volunteers developed diarrhea (D group), and eleven did not (ND group). In the D group, plasma proGN, but not proUGN, concentrations were substantially reduced on days 2 and 3, coinciding with one day after diarrhea onset. No changes were seen in the ND group. ETEC diarrhea also seemed to affect diuresis, the zinc/creatinine ratio, and sodium and chloride secretion levels in urine. ETEC-induced diarrhea causes a reduction in plasma proGN and could potentially be a useful marker for intestinal isotonic fluid loss. [ABSTRACT FROM AUTHOR]

SGLT2 (sodium-glucose cotransporter 2) inhibitors interfere with the reabsorption of glucose and sodium in the early proximal renal tubule, but the magnitude and duration of any ensuing natriuretic or diuretic effect are the result of an interplay between the degree of upregulation of SGLT2 and sodium-hydrogen exchanger 3, the extent to which downstream compensatory tubular mechanisms are activated, and (potentially) the volume set point in individual patients. A comprehensive review and synthesis of available studies reveals several renal response patterns with substantial variation across studies and clinical settings. However, the common observation is an absence of a large acute or chronic diuresis or natriuresis with these agents, either when given alone or combined with other diuretics. This limited response results from the fact that renal compensation to these drugs is rapid and nearly complete within a few days or weeks, preventing progressive volume losses. Nevertheless, the finding that fractional excretion of glucose and lithium (the latter being a marker of proximal sodium reabsorption) persists during long-term treatment with SGLT2 inhibitors indicates that pharmacological tolerance to the effects of these drugs at the level of the proximal tubule does not meaningfully occur. This persistent proximal tubular effect of SGLT2 inhibitors can be hypothesized to produce a durable improvement in the internal set point for volume homeostasis, which may become clinically important during times of fluid expansion. However, it is difficult to know whether a treatment-related change in the volume set point actually occurs or contributes to the effect of these drugs to reduce the risk of major heart failure events. SGLT2 inhibitors exert cardioprotective effects by a direct effect on cardiomyocytes that is independent of the presence of or binding to SGLT2 or the actions of these drugs on the proximal renal tubule. Nevertheless, changes in the volume set point mediated by SGLT2 inhibitors might potentially act cooperatively with the direct favorable molecular and cellular effects of these drugs on cardiomyocytes to mediate their benefits on the development and clinical course of heart failure. [ABSTRACT FROM AUTHOR]

Aims Acetazolamide inhibits proximal tubular sodium and bicarbonate re-absorption and improved decongestive response in acute heart failure in the ADVOR trial. It is unknown whether bicarbonate levels alter the decongestive response to acetazolamide. Methods and results This is a sub-analysis of the randomized, double-blind, placebo-controlled ADVOR trial that randomized 519 patients with acute heart failure and volume overload in a 1:1 ratio to intravenous acetazolamide (500 mg/day) or matching placebo on top of standardized intravenous loop diuretics (dose equivalent of twice oral maintenance dose). The primary endpoint was complete decongestion after 3 days of treatment (morning of day 4). Impact of baseline HCO3 levels on the treatment effect of acetazolamide was assessed. : Of the 519 enrolled patients, 516 (99.4%) had a baseline HCO3 measurement. Continuous HCO3 modelling illustrated a higher proportional treatment effect for acetazolamide if baseline HCO3 ≥ 27 mmol/l. A total of 234 (45%) had a baseline HCO3 ≥ 27 mmol/l. Randomization towards acetazolamide improved decongestive response over the entire range of baseline HCO3− levels (P = 0.004); however, patients with elevated baseline HCO3 exhibited a significant higher response to acetazolamide [primary endpoint: no vs. elevated HCO3; OR 1.37 (0.79–2.37) vs. OR 2.39 (1.35–4.22), P -interaction = 0.065), with higher proportional diuretic and natriuretic response (both P -interaction < 0.001), greater reduction in congestion score on consecutive days (treatment × time by HCO3-interaction <0.001) and length of stay (P -interaction = 0.019). The larger proportional treatment effect was mainly explained by the development of diminished decongestive response in the placebo arm (loop diuretics only), both with regard to reaching the primary endpoint of decongestion as well as reduction in congestion score. Development of elevated HCO3 further worsened decongestive response in the placebo arm (P -interaction = 0.041). A loop diuretic only strategy was associated with an increase in the HCO3 during the treatment phase which was prevented by acetazolamide (day 3: placebo 74.8% vs. acetazolamide 41.3%, P < 0.001). Conclusion Acetazolamide improves decongestive response over the entire range of HCO3− levels; however, the treatment response is magnified in patients with baseline or loop diuretic-induced elevated HCO3 (marker of proximal nephron NaHCO3 retention) by specifically counteracting this component of diuretic resistance. [ABSTRACT FROM AUTHOR]

Aim. To analyze the clinical significance of the sodium level in a single urine test obtained 2 hours after the first dose of a loop diuretic was administered in patients with acute decompensation of chronic heart failure (ADHF).Material and methods. An observational study was conducted on the basis of a rapid-care hospital. The concentration of sodium in urine analysis obtained 2 hours after intravenous administration of the first dose of loop diuretic and natriuresis for the first day of hospitalization were evaluated. The development of resistance to diuretics was taken as the primary endpoint (the need to increase the daily dose of furosemide by more than 2 times compared to the initial one or the addition of another class of diuretic drugs).Results. 25 patients with ADHF were included. The average age of patients was 69.0±14.8 years, 16 (64%) of them were men. The average left ventricular ejection fraction was 49.0±13.5%. The level of the N‐terminal fragment of the brain natriuretic peptide (NT-proBNP) was 3416 (2128; 5781) pg/ml. The average sodium concentration in the urine analysis obtained 2 hours after the start of treatment was 100.6±41.0 mmol / l. The concentration of sodium in urine for the first day was 102.2±39.0 mmol/l. 2 hours after the start of treatment, the sodium concentration in a single urine test was less than 50 mmol/l in 5 (20%) patients. Upon further observation, oligoanuria (defined as diuresis of less than 400 ml within 24 hours) developed in 2 of them. Oligoanuria was not detected among patients whose sodium concentration was more than 50 mmol/l. The need for escalation (any increase in the dose of a loop diuretic and/or the addition of another class of diuretic drugs) arose in 7 (28%) patients; at the same time, we diagnosed the development of resistance to diuretics in 5 (20%) of them. Resistance to diuretics was more common among patients with a sodium concentration in a single urine test obtained 2 hours after the start of furosemide administration, less than 50 mmol/l (p=0.037); when dividing the recruited patient population into subgroups with a sodium concentration in a single urine test ≥50 mmol/l and

Water balance in the body is achieved by balancing renal and non-renal water losses with corresponding water intake. It is under the control of both the central nervous system, which integrates many parameters of water and electrolyte balance in the body, including inducing important adaptive behavioral responses, and three hormonal systems: vasopressinergic, renin-angiotensin-aldosterone and apelinergic. A lot of research is devoted to the regulation of water-electrolyte metabolism. However, this process is still quite difficult to understand, especially since more and more of its regulators are being discovered over time. One of them is the hormone apelin, an endogenous ligand for the APJ receptor. As is known, the receptor is highly expressed in many organs, such as the brain, heart, liver and kidneys, lungs, and has multidirectional effects.This literature review discusses the main characteristics and features of the regulation of these systems in relation to water-electrolyte metabolism, as well as issues of intersystem interaction and modulation of the effects of apelin.

Barbatic acid, a compound isolated from lichen, has demonstrated a variety of biological activities. In this study, a series of esters based on barbatic acid (6a–q′) were designed, synthesized, and evaluated for their diuretic and litholytic activity at a concentration of 100 μmol/L in vitro. All target compounds were characterized using 1H NMR, 13C NMR, and HRMS, and the spatial structure of compound 6w was confirmed using X-ray crystallography. The biological results showed that some derivatives, including 6c, 6b′, and 6f′, exhibited potent diuretic activity, and 6j and 6m displayed promising litholytic activity. Molecular docking studies further suggested that 6b′ had an optimal binding affinity to WNK1 kinases related to diuresis, while 6j could bind to the bicarbonate transporter CaSR through a variety of forces. These findings indicate that some barbatic acid derivatives could be further developed into novel diuretic agents. [ABSTRACT FROM AUTHOR]

Hydration practices in the view of hip, knee, or spine surgery instruct patients to avoid caffeinated drinks, alcoholic beverages, and sugar-sweetened drinks because they adversely impact body fluid homeostasis. However, some patients might be inclined to not include beer among the prohibited beverages because of its low alcohol content and conflicting evidence about its rehydrating effects. The author of this opinion article discusses the shreds of evidence that establish beer as a drink to avoid prior to orthopedic surgery. [ABSTRACT FROM AUTHOR]

Introduction and aim. Drinking mineral waters are one of the environmental factors that affect the condition of the human body. Of particular interest are therapeutic waters of the Naftussya type, which contain autochthonous microbes and organic oil-like substances and can be considered as a kind of ecosystem. On the other hand, gastrointestinal tract also is an ecosystem that associates a resident microbiota and cells of various phenotypes lining the epithelial wall. We assumed that one of the mechanisms of the therapeutic effect of Naftussya water is the interaction of external and internal ecosystems. This article is the first in a series in support of the hypothesis. Material and methods. The object of clinical-physiological observation were residents of the city of Truskavets' (21 men aged 24-67 years and 8 women 33-76 years) with chronic pyelonephritis in remission. The objects of study: leukocyturia, bacteriuria, components of microbiota, phagocytosis function of neutrophils, leukocytary adaptation index, plasma and urine electrolytes and nitrogenous metabolites. Results. The weekly use of bioactive Naftussya water from the Opaka deposit causes a favorable normalizing effect on the stool microbiota: it increases the reduced content of Bifidobacteria and Lactobacilli, instead it reduces the increased content of pathogenic strains of Escherichia coli, as well as Klebsiela and Proteus. Reduction of dysbacteriosis is accompanied by an increase in the reduced bactericidal capacity of blood neutrophils against E. coli and Staphylococcus aureus, and reduction of bacteriuria and leukocyturia. At the same time, the elevated level of creatinine in the plasma decreases, instead, the decreased levels of sodium and chloride increase. As expected, the daily diuresis and excretion of urea, creatinine, phosphates, calcium, magnesium and chloride increases, but not sodium and uric acid, the concentrations of which in the urine decrease. The described physiologically beneficial effects are interpreted as adaptogenic, which is confirmed by an increase in the reduced leukocyte adaptation index. Conclusion. The healing effect of Naftussya bioactive water is the result of the interaction of external and internal ecosystems. The next article will consider the role of the nervous and endocrine systems in this interaction. [ABSTRACT FROM AUTHOR]