Increased Urine Output Research Articles

Mechanism of traditional drug treatment of cancer-related ascites: through the regulation of IL-6/JAK-STAT3 pathway.

Our clinical observation found that JiJiaoLiHuang Pill (JJLH), a classic traditional Chinese medicine (TCM) formulation, can significantly reduce the abdominal circumference of patients with malignant ascites, increase urine output, and improve the quality of life of patients, with preliminary efficacy. But, the exact mechanism is not yet clear. Based on the above observations, the potential mechanism of action of the treatment was preliminarily explored. We identified active ingredients by constructing a "Chinese medicine ingredient-key target-target" network, and verified them by molecular docking using AutoDock tools and PyMOL. Finally, we conducted preliminary verification of the validated pathways and targets using a mouse model of liver cancer ascites. Network pharmacology analysis obtained the top five active ingredients were quercetin, EUPATIN, kaempferol, Obtucarbamate B, and isorhamnetin and the top five key genes were SRC, HSP90AA1, MAPK1, STAT3, and PIK3CA. Molecular docking showed that all 5 active compounds were closely bound to key target genes (binding energy <-6). The animal experiment results showed that JJLH can significantly reduce abdominal circumference, increase urine output, and exhibit dose-dependent inhibition of the AQP-3/JAK-STAT-3 signaling pathway and the expression of related inflammatory factors. The JJLH potentially inhibits the recurrence of liver cancer malignant ascites through the AQP-3/JAK-STAT-3 pathway and affects the prognosis of MA patients.

Djenkolism: Acute Kidney Injury Unresponsive to Conservative Therapy - A Case Report

Djenkol beans (Archidendron jiringa), a popular food in Southeast Asia, can cause djenkolism—a condition leading to acute kidney injury due to the presence of djenkol acid. This case report details a 26-year-old male who presented with three days of anuria following the consumption of half a kilogram of djenkol beans. Upon admission, he exhibited severe abdominal pain, costovertebral tenderness, and elevated renal markers, leading to a diagnosis of obstructive uropathy caused by djenkolic acid crystals. Initial conservative treatment was ineffective, prompting the need for emergency ureteroscopy and placement of bilateral JJ stents to relieve the obstruction. Post-procedure, the patient experienced significant improvement, with a marked increase in urine output; post-obstructive diuresis in the first 24 hours, and resolution of abdominal pain, alongside improved renal function. This case underscores the importance of recognizing djenkolism as a potential cause of acute kidney injury, and advocating for timely diagnosis and intervention to mitigate kidney damage. Public awareness regarding the risks associated with djenkol consumption is also essential. Keywords: Djenkolism, Obstructive Uropathy, Post-Obstructive Diuresis, Acute Kidney Injury

Combination of diuretics to overcome diuretic resistance in acute heart failure: systematic review and updated network meta-analysis

Abstract Background Diuretic resistance in acute heart failure (AHF) presents a significant therapeutic challenge. While randomized clinical trials (RCTs) have compared various diuretics against furosemide, direct comparisons among these therapies are lacking. This network meta-analysis aims to fill this knowledge gap. Purpose To evaluate the efficacy and safety of various diuretic combination therapies in overcoming diuretic resistance in acute heart failure patients. Methods We conducted a systematic review and network meta-analysis of RCTs from January 2000 to December 2023. These RCTs included hospitalized AHF patients with evidence of diuretic resistance. We applied a frequentist random effects model to perform a network meta-analysis combining a total of 11 diuretic strategies compared with low-dose furosemide (reference group). Primary outcomes were urine output and weight loss at 72 hours. Secondary outcomes included cardiovascular mortality and heart failure hospitalization. The safety endpoint was the incidence of acute kidney injury across different diuretic strategies. Results Empagliflozin and high-dose furosemide showed the highest increase in urine output (SMDs: 363.94, P-score=0.64; and 306.31, P-score=0.68). For weight loss, hydrochlorothiazide led to the greatest losses (SMD: 1.33; P-score=0.20), followed by tolvaptan + furosemide low-dose (SMD: 0.85; P-score=0.43). Dapagliflozin ranked best for reducing heart failure hospitalizations (OR 0.15; P-score=0.94), and empagliflozin had the highest rank for mortality reduction (OR 0.31; P-score=0.91) but without statistical significance for mortality. Empagliflozin also showed a better safety profile (OR: 0.74; 95% CI: 0.32 to 1.71 P-score=0.87), (Figure 1 and 2). Conclusion Our findings indicate that SGLT2 inhibitors are a promising therapeutic avenue to mitigate the challenges of diuretic resistance in AHF, demonstrating potential benefits in enhancing urine output, reducing hospitalization rates, and maintaining favourable safety profile.Network and forest plots for U.O/ weightNetwork and forest plots for HHF/ AKI

Magnetic vagus nerve stimulation ameliorates contrast-induced acute kidney injury by circulating plasma exosomal miR-365-3p

BackgroundContrast-induced acute kidney injury (CI-AKI) is manifested by a rapid decline in renal function occurring within 48–72 h in patients exposed to iodinated contrast media (CM). Although intravenous hydration is currently the effective method confirmed to prevent CI-AKI, it has several drawbacks. Some investigations have demonstrated the nephroprotective effects of vagus nerve stimulation (VNS) against kidney ischemia-reperfusion injury, but no direct research has investigated the use of VNS for treating CI-AKI. Additionally, most current VNS treatment applies invasive electrical stimulator implantation, which is largely limited by the complications. Our recent publications introduce the magnetic vagus nerve stimulation (mVNS) system pioneered and successfully used for the treatment of myocardial infarction. However, it remains uncertain whether mVNS can mitigate CI-AKI and its specific underlying mechanisms. Therefore, we herein evaluate the potential therapeutic effects of mVNS on CM-induced nephropathy in rats and explore the underlying mechanisms.ResultsmVNS treatment was found to significantly improve the damaged renal function, including the reduction of elevated serum creatinine (Scr), blood urea nitrogen (BUN), and urinary N-acetyl-β-D-glucosaminidase (NAG) with increased urine output. Pathologically, mVNS treatment alleviated the renal tissue structure injury, and suppressed kidney injury molecule-1 (KIM-1) expression and apoptosis in renal tubular epithelial cells. Mechanistically, increased circulating plasma exosomal miR-365-3p after mVNS treatment enhanced the autophagy and reduced CM-induced apoptosis in renal tubular epithelial cells by targeting Ras homolog enriched in brain (Rheb).ConclusionsIn summary, we demonstrated that mVNS can improve CI-AKI through enhanced autophagy and apoptosis inhibition, which depended on plasma exosomal miR-365-3p. Our findings highlight the therapeutic potential of mVNS for CI-AKI in clinical practice. However, further research is needed to determine the optimal stimulation parameters to achieve the best therapeutic effects.Graphical abstract

8142 Endocrine Considerations Prior to Pituitary Tumor Resection

Abstract Disclosure: P. Einafshar: None. T. Delibasi: None. Endocrine Considerations in Pituitary Tumor Resection Introduction: Diabetes Insipidus (DI) is an endocrine condition involving a disturbance to the action of Anti-Diuretic Hormone (ADH) resulting in polyuria, and polydipsia with complications such as severe water and electrolyte disturbances. It can be classified into Central DI which affects the secretion of ADH or Nephrogenic DI which affects peripheral ADH receptors in Distal Convoluted Tubules (DCTs) in the renal system. Both subtypes however present similarly and are usually known to be transient. It is important to consider the most common etiologies contributing to both central and nephrogenic DI as severe complications may arise if not diagnosed and treated promptly. The most important step is to monitor and manage water and electrolytes and avoid excessive water loss which can lead to irreversible complications. This can be accomplished by introducing synthetic ADH called DDAVP or Desmopressin. Case Description: A 57-year-old female was admitted in preparation for a supra-orbital resection of a suprasellar mass. Two hours post-procedure, she was found to have an increase in urine output with her labs notable for a significant acute increase in serum sodium and a decrease in urine osmolality. Upon emergent Endocrinology evaluation, due to concerns of Acute Diabetes Insipidus in the setting of insult to the pituitary stalk, she was started on emergent treatment with IV DDAVP. Her course was complicated with persistent DI resulting in a case of permanent DI requiring out-patient daily treatments with DDAVP. Discussion: Injury to the pituitary stalk resulting in various endocrine abnormalities has been studied involving a trans-sphenoidal resection of pituitary tumors, but there is a paucity of cases reported when patients undergo a supra-orbital surgical approach. It is vital for Endocrinology and Neurosurgical services to be aware of this phenomenon, and a multi-disciplinary approach to patient management should be considered. Furthermore, close follow-up of pituitary hormones in the post-operative setting is imperative in order to avoid severe complications, such as brain damage or poor mental status. We hope to educate residents and fellows about this phenomenon that is rarely reported in the literature but can have profound effects on patient’s quality of life if not considered by the consulting Endocrinology team. References Christ-Crain, M., Winzeler, B., &amp; Refardt, J. (2021). Diagnosis and management of diabetes insipidus for the internist: an update. Journal of internal medicine, 290(1), 73-87. Mutter, C. M., Smith, T., Menze, O., Zakharia, M., &amp; Nguyen, H. (2021). Diabetes insipidus: pathogenesis, diagnosis, and clinical management. Cureus, 13(2). Presentation: 6/1/2024

8067 AVP Gene Mutation: A Rare Cause of Diabetes Insipidus

Abstract Disclosure: N. Navrange: None. M. Williams: None. P. Madhavan: None. Introduction: Arginine vasopressin deficiency (AVP-D), also known as neurohypophyseal or central diabetes insipidus (DI), is marked by a reduced secretion of arginine vasopressin (AVP), resulting in polyuria and polydipsia. AVP-D is a rare disorder, with a prevalence of 1 in 25,000. Typically, the disorder is acquired. However, in less than 5% of cases, it has a genetic etiology. The majority of mutations in the AVP gene are autosomal dominant. Normally, AVP encodes vasopressin, also known as antidiuretic hormone (ADH). It plays a key role in the reabsorption of water in the kidney, the regulation of blood pressure, and controlling the body’s osmotic balance. However, a mutation in this gene leads to a deficient release of ADH, leading to reduced reabsorption of water in the collecting duct and decreased ability to concentrate urine. This results in increased urine output and excessive thirst. The onset and severity of symptoms varies between individuals. Case Report: In this report, we discuss the case of a 40-year-old Caucasian female with familial neurohypophyseal diabetes insipidus. The patient presented to the clinic for follow-up care of DI and hyponatremia. She received her DI diagnosis before the age of 5 and has multiple family members with the condition including her maternal grandfather, mother, and 2 siblings. Additionally, she suspected one of her children was exhibiting excessive urination. Past medical history is also significant for seizure disorder, postpartum cardiomyopathy, Chiari malformation type I and remote history of substance abuse. Vitals were stable with blood pressure of 122/86 mmHg, heart rate of 93 bpm, body mass index of 31.8. Physical exam was unremarkable except for obesity. She is currently managed with DDAVP 0.05 mg twice daily. Previously, imaging was performed to rule out pituitary abnormalities. The patient was referred for genetic testing due to her family history and was found to have a previously described rare autosomal dominant mutation of the AVP protein. The single nucleotide polymorphism in exon 1 results in a missense mutation substituting an alanine nucleotide for threonine (c.55G&amp;gt;A). The patient was counseled to share these results with her children’s pediatrician, as they could benefit from testing for the mutation. Discussion: Our patient has a pathogenic variant in AVP, specifically a missense mutation from Alanine to Threonine at codon 19 of the AVP protein. This mutation is associated with autosomal dominant neurohypophyseal diabetes insipidus. This case provides an example of a rare cause of neurohypophyseal diabetes insipidus and emphasizes the necessity of obtaining detailed family history in patients who have DI and considering genetic testing for patients with suspicion for familial involvement. Presentation: 6/2/2024

12227 The Battle Between Central And Nephrogenic Diabetes Insipidus

Abstract Disclosure: A.A. Luzuriaga Chavez: None. J.P. Hidalgo: None. A. Rao: None. N. Patel: None. Diabetes insipidus (DI) is a rare disorder characterized by excessive polyuria and polydipsia. The two main types include central diabetes insipidus (CDI), which results from antidiuretic hormone (ADH) deficiency and nephrogenic diabetes insipidus (NDI), defined by ADH resistance in the renal tubules. It can be challenging to distinguish between different types of DI in a critically ill patient. A 68-year-old female with a past medical history of hypertension, bipolar disorder came to the ER for complaints of chills and shortness of breath. She was transferred to the intensive care unit (ICU) for septic shock secondary to pneumonia and left pleural effusion. A chest tube was placed with improvement in her breathing and she was transferred out of the ICU. Four days later, the patient developed altered mental status, fevers and ICU was reconsulted due to concern for meningitis. A lumbar puncture was done with negative results but the brain MRI revealed ischemic sites involving both medial parietal cortices extending into both occipital poles, consistent with acute ischemia. Furthermore, the patient developed an increased urine output of 200ml per hour with a negative balance of 2.7L, increased sodium of 150, serum osmolality of 313 and urine osmolality of 196. The patient received desmopressin 1 mcg q 6 hrs with the persistence of hypernatremia. Upon further questioning, the patient had been on lithium therapy in the past for bipolar disorder. Amiloride 2.5mg BID was added to the treatment regimen. The patient’s hypernatremia and urine output improved and she was discharged on both amiloride and desmopressin to follow up for dose adjustments as needed. DI has a prevalence of 1 in 25000. Acquired CDI secondary to lesions in the hypophysis or hypothalamus highlights the major role of the central nervous system in regulating water homeostasis. This case report describes CDI developing after a stroke. Ischemia can cause hypoperfusion of osmoreceptors in the hypothalamus and posterior pituitary. Lithium can be frequently associated with NDI, usually seen in 20 to 40% of patients. Different mechanisms of action include lithium interference in renal collecting tubules by increasing cAMP in response to ADH and down-regulation of aquaporin-2 expression, which is accepted to be reversible with the cessation of the therapy. However, long-term treatment with lithium likely results in permanent NDI. Our patient had a history of lithium therapy which contributed to the development of symptoms of NDI and responded to a combination of desmopressin and amiloride. The successful therapy enforces the diagnosis of both a central and a peripheral pathology. Central and nephrogenic DI, despite stemming from distinct underlying causes, may concurrently manifest in critically ill patients. This case report emphasizes the need for physicians to evaluate for multiple causes of DI in a patient with water disturbances. Presentation: 6/1/2024

Tolvaptan and the role of kidney aquaporin-2 abundance in managing volume overload in patients with CKD

ABSTRACT Objective This retrospective study evaluated tolvaptan's efficacy, safety, and predictive indicators in managing volume overload in chronic kidney disease (CKD) patients. Methods CKD patients with volume overload, treated with loop diuretics alone or with tolvaptan at Zhongda Hospital, Southeast University, from 1 March 2022 to 31 December 2023, were included. Patients were divided into loop diuretic (Group C) and loop diuretic combined with tolvaptan (Group T) cohorts. Primary outcomes included volume control, changes in weight, urine output, and laboratory parameters within 1 week post-medication. Adverse events such as hypernatremia and hyperkalemia, etc., were recorded. We further conducted immunohistochemical staining of renal biopsy tissues to investigate the roles of aquaporin-2 (AQP2) in the collecting duct and plasma albumin in predicting the efficacy of tolvaptan. Results Of 174 CKD patients with volume overload, 108 (67.07%) were male. Group C and Group T each comprised 87 patients. At baseline, no significant differences in urine output and weight were noted. By day 3, Group T exhibited a greater increase in urine output (P &amp;lt; .001) and weight reduction (P &amp;lt; .001). At day 7, Group T maintained more significant diuretic effects (P &amp;lt; .001). More Group C patients required ultrafiltration therapy (P = .040). Adverse event rates did not significantly differ. Notably, AQP2 expression in the collecting duct may predict tolvaptan responsiveness, while plasma albumin did not affect efficacy. Conclusion Tolvaptan showed efficacy and safety in managing volume overload in CKD patients. The expression of AQP2 in the collecting duct could predict tolvaptan's efficacy. This study protocol was approved by the Ethics Committee of Zhongda Hospital Affiliated to Southeast University (Approval No. 2023ZDSYLL180-P01, Clinical Trial Registration No. ChiCTR2300075274, Trial Registration Link: https://www.chictr.org.cn/guide.html).

Propofol-induced transient arginine vasopressin deficiency.

We describe and characterise the case of a 26-year-old female undergoing surgery for a right-sided sinonasal alveolar rhabdomyosarcoma who developed profound, transient arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus (DI)) associated with anaesthesia. In this case report, we characterise the development of AVP-D with serial copeptin and paired urine and serum osmolality measurements. Based on the anaesthetic agent's profile and the literature, we attribute this presentation to propofol exposure. We present a description of the literature on anaesthesia-associated DI as well as poignant learning points. Exposure to anaesthetic agents is a rare cause of self-limited but sudden and profound arginine vasopressin deficiency (AVP-D) or arginine vasopressin resistance (AVP-R). Sevoflurane has been associated with AVP-R and propofol with AVP-D, although the responsible agent may be difficult to identify. Differentiation of AVP-R and AVP-D can be made based on copeptin concentration, where available, or clinical response to desmopressin. Whilst the patient is anaesthetised, intravenous fluid replacement should be targeted to match urine output until the patient is able to drink to thirst. This should be clearly communicated to staff and the patient. Rapid resolution of AVP-R/AVP-D when the causative agent is discontinued has been reported with both propofol and sevoflurane. As such, switching the agent used to maintain anaesthesia may terminate increased urine output in a clinically meaningful timeframe.

Effects of Composite Probiotic Food on Urinary, Serum Biochemical and Oxidative Stress Parameters in a Urolithiatic Rat Model.

Prevention, management or cure of diseases through dietary approaches is becoming increasingly important. Research suggests that probiotic, oxalate-degrading Lactobacillus species administered via a milk and cereal food can prevent kidney stones while also addressing nutritional deficiencies and maintaining essential calcium levels. This study investigates the effect of a composite probiotic milk beverage on urolithiatic rats. Probiotic milk-barley beverage (PMBB) was prepared by fermentation of milk enriched with barley (Hordeum vulgare) flour using starter culture containing oxalate-degrading probiotic strains (Lacticaseibacillus rhamnosus strains MTCC5945 and MTCC25062, Lactobacillus helveticus MTCC5463 and Lactiplantibacillus plantarum M11). Cumin and common salt were used as flavourings. Unfermented milk-barley base (C) served as control. Wistar rats were divided in four groups (N=6). Normal control (NC) group received normal rat diet, and to induce kidney stones, ethylene glycol (0.75 %) and ammonium chloride (1 %) were administered to the disease control (DC) group, PMBB and control (C) groups for 28 days. PMBB and C groups received 1 mL of probiotic milk and barley beverage and unfermented milk-barley base from day 15 to day 28. Indicators of urolithiasis were studied. PMBB significantly (p<0.05) increased urine output, decreased urine oxalate concentrations and increased creatinine, calcium and uric acid concentrations. Serum parameters such as concentrations of calcium, uric acid, urea and creatinine increased significantly (p<0.05) in DC rats, but decreased significantly (p<0.05) in the PMBB group. In addition, serum concentrations of magnesium and osteopontin decreased more significantly in DC rats than in the PMBB ones. The increase in malondialdehyde and decrease in reduced glutathione concentrations observed in the DC group were significantly lower in the PMBB group. The histomorphology of the kidney tissue of DC rats showed calcium oxalate crystal aggregates in the tubules, indicators of renal injury, tubular dilatation, enlarged urinary space and shrunken glomeruli. The PMBB group showed an improvement in the renal histological architecture. Analysis of the caecal digesta of the rats showed a significantly (p<0.05) higher mass fraction of fatty acids (acetic and propionic) in the treatment group. The results show the potential of PMBB in the dietary control of urolithiasis. This study focuses on the antiurolithiatic prospect of a composite probiotic milk beverage produced with oxalate-degrading culture. It also points to a new functional food form that shows promising health benefits in nutrition of patients with urolithiasis.

Torsemide in Edema Associated with Chronic Kidney Disease.

Torsemide is a loop diuretic used to manage edema associated with chronic kidney disease (CKD) and acute kidney injury (AKI). It acts by inhibiting sodium and chloride ions reabsorption in the ascending limb of the loop of Henle, thereby increasing urine output and reducing fluid accumulation. Compared to other diuretics, torsemide has an extended duration of action, higher bioavailability, and its elimination route is primarily through the hepatic route, making it effective in patients with CKD and AKI. Clinical studies indicate that torsemide can improve symptoms of fluid overload and potentially enhance renal function.

Identifying Early Risk Factors for Postoperative Pulmonary Complications in Cardiac Surgery Patients.

Background and Objectives: Postoperative pulmonary complications (PPCs) are common in patients who undergo cardiac surgery and are widely acknowledged as significant contributors to increased morbidity, mortality rates, prolonged hospital stays, and healthcare costs. Clinical manifestations of PPCs can vary from mild to severe symptoms, with different radiological findings and varying incidence. Detecting early signs and identifying influencing factors of PPCs is essential to prevent patients from further complications. Our study aimed to determine the frequency, types, and risk factors significant for each PPC on the first postoperative day. The main goal of this study was to identify the incidence of pleural effusion (right-sided, left-sided, or bilateral), atelectasis, pulmonary edema, and pneumothorax as well as detect specific factors related to its development. Materials and Methods: This study was a retrospective single-center trial. It involved 314 adult patients scheduled for elective open-heart surgery under CPB. Results: Of the 314 patients reviewed, 42% developed PPCs within 12 h post-surgery. Up to 60.6% experienced one PPC, while 35.6% developed two PPCs. Pleural effusion was the most frequently observed complication in 89 patients. Left-sided effusion was the most common, presenting in 45 cases. Regression analysis showed a significant association between left-sided pleural effusion development and moderate hypoalbuminemia. Valve surgery was associated with reduced risk for left-sided effusion. Independent parameters for bilateral effusion include increased urine output and longer ICU stays. Higher BMI was inversely related to the risk of pulmonary edema. Conclusions: At least one PPC developed in almost half of the patients. Left-sided pleural effusion was the most common PPC, with hypoalbuminemia as a risk factor for effusion development. Atelectasis was the second most common. Bilateral effusion was the third most common PPC, significantly related to increased urine output. BMI was an independent risk factor for pulmonary edema development.

Perioperative fluid management for adult cardiac surgery: network meta-analysis pooling on twenty randomised controlled trials

BackgroundThe aim of this study was to evaluate colloids and crystalloids used in perioperative fluid therapy for cardiac surgery patients to further investigate the optimal management strategies of different solutions.MethodRCTs about adult surgical patients allocated to receive perioperative fluid therapy for electronic databases, including Ovid MEDLINE, EMBase, and Cochrane Central Register of Controlled Trials, were searched up to February 15, 2023.ResultsNone of the results based on network comparisons, including mortality, transfuse PLA, postoperative chest tube output over the first 24 h following surgery, and length of hospital stay, were statistically significant. Due to the small number of included studies, the results, including acute kidney injury, serum creatinine, serum microglobulin, and blood urea nitrogen, are from the direct comparison. For transfusion of RBCs, significant differences were observed in the comparisons of 3% gelatine vs. 6% HES 200/0.5, 4% albumin vs. 5% albumin, 4% gelatine vs. 5% albumin, 5% albumin vs. 6% HES 200/0.5, and 6% HES 130/0.4 vs. 6% HES 200/0.5. In transfusion of FFP, significant differences were observed in comparisons of 3% gelatine vs. 4% gelatine, 3% gelatine vs. 6% HES 200/0.5, 5% albumin vs. 6% HES 200/0.5, 4% gelatine vs. 5% albumin, 4% gelatine vs. 6% HES 200/0.4, and 6% HES 130/0.4 vs. 6% HES 200/0.5. For urinary output at 24 h after surgery, the results are deposited in the main text.ConclusionThis study showed that 3% gelatin and 5% albumin can reduce the transfuse RBC and FFP. In addition, the use of hypertonic saline solution can increase urine output, and 5% albumin and 6% HES can shorten the length of ICU stay. However, none of the perioperative fluids showed an objective advantage in various outcomes, including mortality, transfuse PLA, postoperative chest tube output over the first 24 h following surgery, and length of hospital stay. The reliable and sufficient evidences on the injury of the kidney, including acute kidney injury, serum creatinine, serum microglobulin, and blood urea nitrogen, was still lacking. In general, perioperative fluids had advantages and disadvantages, and there were no evidences to support the recommendation of the optimal perioperative fluid for cardiac surgery.

Increased water intake dilutes protective uromodulin levels in urine and results in increased rates of pyelonephritis in a murine model.

Urinary tract infections (UTIs) rank among the most prevalent infections in humans, carrying substantial implications for public health. Women experiencing recurrent UTIs are often advised to boost their fluid intake to help eliminate bacteria. In this study, we explored the impact of elevated fluid consumption during UTIs using a mouse model of pyelonephritis. UTI was induced in 8-10 w female BALB/cJ-mice by surgically injecting Escherichia coli (O6:K13:H1) into the bladder whereafter mice were randomized to gel food (GF) or regular chow. Immune response and infection severity were determined 24-h post-infection. Invitro bacterial growth (OD600) was determined in urine from mice or from human volunteers. Gel feeding increased urine output (1.40 ± 0.77 μL min-1, p < 0.01) and diluted the urine (668.7 ± 177 mOsmol kg-1, p < 0.0001) compared to controls on regular chow (urine output: 0.34 ± 0.27 μL min-1, osmolality: 1439 ± 473.5 mOsmol kg-1). Mice on GF had a higher risk of pyelonephritis (87.5%) and more severe infections (26.22 ± 9.88 CFU mg-1 tissue) compared to controls (43.75%; 3.87 ± 3.56 CFU mg-1, p < 0.01). Correspondingly, the growth of E.coli was markedly reduced at osmolalities above 1200 mOsmol kg-1 compared to 600 mOsmol kg-1 and GF mice had lower urine levels of uromodulin (13.70 ± 1.89 μg mL-1, p < 0.01) compared to controls (24.65 ± 2.70 μg mL-1). Increased water intake and urine flow in mice will markedly increase the risk of pyelonephritis. The increased risk may reflect reduced urine uromodulin combined with optimized growth conditions for E. coli. The study does not immediately support the notion that established UTIs can be eliminated by increased water intake.

Synthetic Angiotensin II ameliorates alterations of systemic hemodynamics, microcirculatory deterioration, and renal damage in septic rats

IntroductionSeptic shock is a systemic infection that causes persistent systemic hypotension, inflammation, tissue hypoperfusion and acute kidney injury (AKI). Despite norepinephrine being the currently recommended vasopressor agent, an alternative vasopressor agent that positively affects peripheral and organ microcirculatory perfusion and oxygenation is needed. This study investigated a new synthetic Angiotensin II agent suitable for improving microcirculatory parameters in a rat model of sepsis-induced systemic hemodynamic dysfunction. Methods48 mechanically ventilated, anesthetized male rats were allocated as control; lipopolysaccharide (LPS, 20 mg/kg) and LPS groups received either ringer acetate (RA), norepinephrine (NE), Angiotensin II (Ang II), or a combination of NE and Ang II. Systemic hemodynamics, renal cortical pO2 and perfusion, and muscle microcirculatory oxygen saturation were evaluated. ResultsMAP was restored in all LPS groups that received Ang II, NE, and NE + Ang II compared to the LPS group alone (p < 0.05). The deterioration of renal microcirculatory cortical oxygen, oxygen delivery, and consumption after sepsis was not restored by any of the resuscitation strategies. However, urine output was improved after Ang II resuscitation compared to the LPS and LPS + RA groups (p < 0.05). Furthermore, the muscle capillary oxygen saturation and functional capillary density (FCD) were improved by a combined infusion of NE and Ang II (p < 0.05). ConclusionsAng II can improve the MAP in rats in a way comparable to norepinephrine. Ang II increased urine output and muscle capillary oxygenation and reduced renal tissue damage. Our study supports that broad-spectrum vasopressors can benefit tissue perfusion and oxygenation in the resuscitation of septic patients.

Cannabinoid receptor type 1 activation causes a water diuresis by inducing an acute central diabetes insipidus in mice.

Cannabis and synthetic cannabinoid consumption are increasing worldwide. Cannabis contains numerous phytocannabinoids that act on the G protein-coupled cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 expressed throughout the body, including the kidney. Essentially every organ, including the kidney, produces endocannabinoids, which are endogenous ligands to these receptors. Cannabinoids acutely increase urine output in rodents and humans, thus potentially influencing total body water and electrolyte homeostasis. As the kidney collecting duct (CD) regulates total body water, acid/base, and electrolyte balance through specific functions of principal cells (PCs) and intercalated cells (ICs), we examined the cell-specific immunolocalization of CB1R in the mouse CD. Antibodies against either the C-terminus or N-terminus of CB1R consistently labeled aquaporin 2 (AQP2)-negative cells in the cortical and medullary CD and thus presumably ICs. Given the well-established role of ICs in urinary acidification, we used a clearance approach in mice that were acid loaded with 280 mM NH4Cl for 7 days and nonacid-loaded mice treated with the cannabinoid receptor agonist WIN55,212-2 (WIN) or a vehicle control. Although WIN had no effect on urinary acidification, these WIN-treated mice had less apical + subapical AQP2 expression in PCs compared with controls and developed acute diabetes insipidus associated with the excretion of large volumes of dilute urine. Mice maximally concentrated their urine when WIN and 1-desamino-8-d-arginine vasopressin [desmopressin (DDAVP)] were coadministered, consistent with central rather than nephrogenic diabetes insipidus. Although ICs express CB1R, the physiological role of CB1R in this cell type remains to be determined.NEW & NOTEWORTHY The CB1R agonist WIN55,212-2 induces central diabetes insipidus in mice. This research integrates existing knowledge regarding the diuretic effects of cannabinoids and the influence of CB1R on vasopressin secretion while adding new mechanistic insights about total body water homeostasis. Our findings provide a deeper understanding about the potential clinical impact of cannabinoids on human physiology and may help identify targets for novel therapeutics to treat water and electrolyte disorders such as hyponatremia and volume overload.

Recurrent hyponatremia in neonate: a case of renal salt wasting syndrome

BackgroundRenal salt wasting (RSW) is primarily seen with central nervous disorders and is characterized by hyponatremia, elevated urinary sodium excretion, increased urine output, and hypovolemia. Although there have been reports of RSW in children, it has not been reported in newborns.Case presentationA term (38 weeks 2 days) female weighing 2060 g, born via normal vaginal delivery, to a primi-gravida mother, was admitted to our neonatal intensive care unit. At birth, the baby was non-vigorous, had aspirated meconium, and required bag-and-mask ventilation following which the baby cried. The child was put on CPAP and inotropes for respiratory distress and shock, respectively, along with first-line antibiotics. Over the next few days, the child was weaned off CPAP, inotropes were stopped, and feeds were started. On postnatal day (PND) 8, the baby developed repeated episodes of seizures requiring two-antiepileptics followed by midazolam infusion, had shock requiring inotropes, and also had a tense anterior fontanelle with altered sensorium and tone changes, for which mannitol and 3% saline were given. Antibiotics were upgraded, and neuroimaging (MRI) revealed left basal-ganglia bleed with intraventricular extension and cerebral venous thrombosis. The baby showed gradual clinical improvement with the above measures and was restarted on feeds. However, from PND-19 onwards the baby had repeated episodes of hyponatremia requiring 3% saline infusions, progressive weight loss, and polyuria. Considering RSW, urine sodium was done which was high (110 mmol/L). For polyuria and weight loss, feed volume was increased, whereas, for hyponatremia, table salt was added to the expressed breast milk (1 gm × tds). Subsequently, all the serum sodium values remained within normal limits, and the baby started gaining weight and was discharged on similar advice (PND 38). On further follow-up, table salt was gradually decreased in the feeds and was stopped after 1 month of discharge with normal serum sodium values.ConclusionManagement of recurrent hyponatremia in a neonate is challenging. Despite its rarity, RSW in newborns should be considered a differential.

Evaluation of diuretic activity of hydroalcoholic extract of Leptadenia pyrotechnica in rats

In traditional Indian medicine, the whole plant of Leptadenia pyrotechnica (Asclepiadaceae) is said to have a strong diuretic effect. The aim of this study was to evaluate the diuretic potential of the hydroalcoholic extract of Leptadenia pyrotechnica (HALPE) in rats. Group I, control (0.5% CMC saline, 10 ml/kg, b.w.), group II, furosemide (10 mg/kg b.w.) as a standard drug, and different concentrations of L.P. (100, 200, and 400 mg/kg b.w.) were administered intraperitoneally (n = 5 per treatment group) to hydrated rats, and their urine output was monitored at 6 h, 12 h, and 18 h after drug administration. The diuretic effect of the extract was highly significant compared to control animals. Halpe at a dose of 400 mg/kg shows a significant increase in urine volume with increased urine output. This study suggests that the active component of L.P. had a diuretic effect similar to that of furosemide. These results confirm the traditional use of Leptadenia pyrotechnica as a diuretic agent. Since ancient times, medicinal plants, sometimes called herbs, have been used in various traditional medical procedures. Leptadenia pyrotechnica is a plant commonly known as the chimp. It is traditionally used in rural areas for the treatment of many diseases, such as antifungal, antibacterial, anticancer, antioxidant, wound healing, anthelmintic, atherosclerosis, hypolipidemia, diuretic, diabetes, and hepatoprotective. In rural areas, this plant is also used as medicine and as a vegetable. First, the plants are dried and turned into powder, which is then used as a paste for ringworm, antifungal, wound treatment, and new plants for many other diseases.

#370 Macroscopic hematuria-associated severe acute kidney injury from thin basement membrane disease

Abstract Background Macroscopic hematuria-associated acute kidney injury (MH-AKI) is a rare condition reported in IgA nephropathy and others, and the mechanism of renal tubular damage caused by red blood cells in the tubules appears to be similar to that of anticoagulant nephropathy. Case presentation A 66-year-old Japanese woman with no previous medical history was referred to our hospital with anuric severe kidney injury. Seven days earlier, she had transient acute lumbar back pain, which was followed by gradual worsening of malaise and loss of appetite. On admission, her serum BUN was 147.8 mg/dL, serum Cr 18.57 mg/dL, hemoglobin 11.2 g/dL, urinary red blood cells&amp;gt; 100/HPF, urinary protein 28.8 g/gCr, no hydronephrosis in either kidney, but a small stone in the right kidney. After admission, while starting hemodialysis, she was treated with methylprednisone 1000 mg for 3 days followed by prednisone 40 mg/day because of suspected rapidly progressive glomerulonephritis, but both MPO-/PR3-ANCA and anti-GBM antibodies were negative. Renal biopsy from left kidney showed acute tubular injury with large amounts of red blood cells and red blood cell casts filling the distal tubules (Figure), and prednisone was discontinued. Subsequently, urine flowed out with gross hematuria, and her hematuria and renal function improved with increased urine output, and she was weaned from hemodialysis. Electron microscopy showed glomerular thin basement membrane (TBMD) (Figure). Her renal function and hematuria slowly improved and the right kidney stone disappeared. Microscopic hematuria eventually disappeared, and her serum Cr level was 1.1 mg/dL one year after onset. Conclusions This is the first report of MH-AKI in TBMD without a background of anticoagulation, severe thrombocytopaenia, or iron overload. In one report, compared to IgA nephropathy, TBMD is associated with increased urinary Ca and uric acid excretion, which is associated with gross hematuria and back pain [1]. In this case of MH-AKI from TBMD, both red blood cells and crystal formation in the tubular lumens may have transiently and synergistically caused renal tubular obstruction and heme iron-induced tubular damage.

#1651 Urinary oxygen partial pressure: closely associated with hourly urine output induced by furosemide in patients with acute renal injury

Abstract Background and Aims Urine oxygen level, an indicator of kidney medullar oxygenation, is promising for predicting the onset of acute kidney injury (AKI). Furosemide, a commonly used diuretic in ICU, significantly increases urine output and is believed to change kidney medullar oxygenation. We monitored the longitudinal change of urinary oxygen partial pressure during bolus or pump administration of furosemide, aiming to describe the reaction pattern in an AKI-susceptible patient population. Method The prospective observational pilot study included seven adult patients in the ICU because of cardiac surgery or sepsis. We monitored the continuous urinary oxygen partial pressure for 8-24 hours through a device placed between the urinary catheter and collecting bag during furosemide administration, recorded hourly urine output simultaneously from a urine bag, and followed the patients in the hospital for the onset and development of AKI. Results We recruited three female patients and four male patients with an average age of 54 years and a medium of 5 days in ICU with an AKIN stage I of AKI during their hospital stay. None of them developed more severe stage AKI or required any kidney replacement therapy. We found a reverse correlation pattern between hourly urine output and urinary oxygen partial pressure. Specifically, the urine oxygen level dropped during urine volume increase caused by furosemide bolus administration and abolished by furosemide administration through a pump with more stable urine output. The paired t-test showed a significant increase in average urine oxygen level (mean difference = 21.2 mmHg, p = 0.044) recorded during the “high hourly urine output” period compared to the “low hourly urine period”. Conclusion We first found a drop in urinary oxygen partial pressure during the high urine output period elicited by bolus furosemide administration. It shed light on the confounding factors in AKI predicating during possible furosemide administration.