Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure.

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

Hydronephrotic lower moiety of duplex systems: Observations using diuresis renography.

PURPOSE: The purpose of this study is to characterize the prevalence and behavior of hydronephrosis of non-refluxing lower moiety of duplex kidneys using MAG-3 diuresis renography. We compare our data to previous case series and ureteropelvic junction obstruction of single systems. MATERIALS AND METHODS: An IRB-approved database of over 5000 diuresis renograms performed in 2025 patients was queried to identify cases of hydronephrosis of lower moiety of duplex kidneys suspicious for ureteropelvic obstruction, excluding those with hydroureter or reflux. Kidney function and post-furosemide drainage parameters on initial and follow-up diuresis renograms were recorded. Medical records and patient outcomes were reviewed. RESULTS: In total, 19 renal units were identified in 18 patients (11 male, 7 female), age range 0.5 months to 17.8 years, including one patient with bilateral lower moiety hydronephrosis. Initial diuresis renograms in 12 asymptomatic patients (13 renal units) with antenatal hydronephrosis demonstrated varying drainage patterns from normal to obstructed. Follow-up studies showed worsening drainage in 3 patients, who all underwent surgery. Drainage improved in 4 patients and remained unchanged in 5 patients (6 renal units). Of the 6 patients presenting with Dietl's crisis, 5 showed obstructive drainage on initial diuresis renogram, 2/5 with decreased function. All 5 obstructed patients underwent surgery. CONCLUSION: Hydronephrosis of the lower moiety of a duplex system is rare and behaves similarly to single systems. The majority are diagnosed antenatally, display a dynamic nature, and may present with acute obstruction. Diuresis renography is a valuable tool in its evaluation and management.

Post-obstructive diuresis after posterior urethral valve treatment in neonates: a retrospective cohort study.

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

Impact of forced diuresis at two different time points on pelvic imaging in prostatic carcinoma with 68 Ga-PSMA PET/CT.

OBJECTIVE: We compared diagnostic quality of 68 Ga-PSMA PET/CT imaging focused on the pelvic structures using two furosemide protocols in two different groups of patients. MATERIAL AND METHODS: A total of 55 patients with prostate cancer were retrospectively enrolled in the study. Out of 55, 31 patients were in group 1 (median age: 66 years, Range 44-78 years) in which furosemide injection was given after completion of whole-body 68 Ga-PSMA PET/CT scan and 24 patients were in group 2 (median age: 63.5 years, range: 50-82 years) in which it was given along with the 68 Ga-PSMA injection. In both groups, an initial time point scan (T0 scan) and a delayed time point scan (T1scan) were done. The images were analyzed qualitatively as well as quantitatively. RESULTS: Quantitatively there was no statistically significant difference between the SUVmax and T:B of prostatic lesion and seminal vesicle invasion (SVI) in both the groups at two time points ( P  > 0.05). Early furosemide injection caused a washout of the urinary bladder radiotracer concentration in significantly higher number of patients in group 2 (62.5% vs. 6.45% patients, P  < 0.001). There was significant clearance of radiotracer activity from the ureters in group 2 (SUVmax: 9.28 vs. 3.09, P  = 0.002). CONCLUSION: The simultaneous furosemide and 68 Ga-PSMA injection can reduce the urinary excretion of the tracer and improve the diagnostic confidence of prostatic lesion, SVI and lymph nodal metastasis, along with reducing the scanning time and radiation burden, making this protocol an effective alternative to the present protocol of delayed furosemide injection.

Reduced heart failure-related healthcare costs with Furoscix versus in-hospital intravenous diuresis in heart failure patients: the FREEDOM-HF study.

Aim: Compare heart failure (HF) costs of Furoscix use at home compared with inpatient intravenous (IV) diuresis. Patients & methods: Prospective, case control study of chronic HF patients presenting to emergency department (ED) with worsening congestion discharged to receive Furoscix 80 mg/10 ml 5-h subcutaneous infusion for ≤7 days. 30-day HF-related costs in Furoscix group derived from commercial claims database compared with matched historical patients hospitalized for <72 h. Results: Of 24 Furoscix patients, 1 (4.2%) was hospitalized in 30-day period. 66 control patients identified and were well-matched for age, sex, ejection fraction (EF), renal function and other comorbidities. Furoscix patients had reduced mean per patient HF-related healthcare cost of $16,995 (p < 0.001). Conclusion: Furoscix use was associated with significant reductions in 30-day HF-related healthcare costs versus matched hospitalized controls.

What is this article about? In heart failure (HF), the heart cannot pump as well as it should. This causes blood to back up in the vessels that return blood to the heart. Fluid leaks from these vessels and collects in vital organs such as the lungs. This fluid build-up is called congestion. Congestion causes symptoms such as shortness of breath, tiredness and leg swelling. Furoscix is a prescription medicine, a diuretic, that treats congestion. Diuretics help get rid of extra fluid by increasing urination. Congestion is usually managed with oral diuretics, but sometimes congestion cannot be controlled by oral diuretics and patients may have to spend several days at a clinic or hospital to receive diuretics given through a vein (intravenous or iv.). Furoscix is a new formulation of furosemide, a common diuretic, and is delivered into the skin (subcutaneous) by a self-administered pump instead of through an iv. Our investigation aimed to answer two questions Can Furoscix be given to patients at home instead of in the hospital with iv. diuretics? Is there a cost savings to using Furoscix? Instead of being admitted to the hospital for iv. diuretics, HF patients with worsening congestion who came to the emergency department were sent home to receive Furoscix 80 mg/10 ml 5-h subcutaneous infusion for ≤7 days. 30-day costs related to HF in these patients were compared with costs from similar group of patients previously hospitalized for iv. diuretics. What were the results & what do they mean? In patients who needed to be admitted to the hospital for iv. diuretics, Furoscix given at home instead reduced congestion and resulted in significant cost savings. Patients with heart failure, who are not getting relief with oral diuretics, can be treated with Furoscix at home without having to be admitted to the hospital for iv. diuretics. Use of Furoscix instead of iv. furosemide can save money to the healthcare system.

The Reason Beer Makes You Pee and Why You Should Abstain before Orthopedic Surgery.

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.

Combined forced diuresis and late acquisition on [68Ga]Ga-PSMA-11 PET/CT for biochemical recurrent prostate cancer: a clinical practice-oriented study.

OBJECTIVES: Increased detection of prostate cancer (PCa) recurrences using [68Ga]Ga-PSMA-11 PET/CT has been reported by adding forced diuresis or late-phase imaging to the standard protocol. However, the combination of these procedures in the clinical setting is still not standardized. METHODS: One hundred prospectively recruited biochemical recurrent PCa patients were restaged with dual-phase [68Ga]Ga-PSMA-11 PET/CT from September 2020 to October 2021. All patients received a standard scan (60 min), followed by diuretics (140 min) and a late-phase abdominopelvic scan (180 min). PET readers with low (n = 2), intermediate (n = 2), or high (n = 2) experience rated (i) standard and (ii) standard + forced diuresis late-phase images in a stepwise fashion according to E-PSMA guidelines, scoring their level of confidence. Study endpoints were (i) accuracy against a composite reference standard, (ii) reader's confidence level, and (iii) interobserver agreement. RESULTS: Forced diuresis late-phase imaging increased the reader's confidence category for local and nodal restaging (both p < 0.0001), and the interobserver agreement in identifying nodal recurrences (from moderate to substantial, p < 0.01). However, it significantly increased diagnostic accuracy exclusively for local uptakes rated by low-experienced readers (from 76.5 to 84%, p = 0.05) and for nodal uptakes rated as uncertain at standard imaging (from 68.1 to 78.5%, p < 0.05). In this framework, SUVmax kinetics resulted in an independent predictor of PCa recurrence compared to standard metrics, potentially guiding the dual-phase PET/CT interpretation. CONCLUSIONS: The present results do not support the systematic combination of forced diuresis and late-phase imaging in the clinical setting, but allow the identification of patients-, lesions-, and reader-based scenarios that might benefit from it. KEY POINTS: • Increased detection of prostate cancer recurrences has been reported by adding diuretics administration or an additional late abdominopelvic scan to the standard [68Ga]Ga-PSMA-11 PET/CT procedure. • We verified the added value of combined forced diuresis and delayed imaging, showing that this protocol only slightly increases the diagnostic accuracy of [68Ga]Ga-PSMA-11 PET/CT, thus not justifying its systematic use in clinics. • However, it can be helpful in specific clinical scenarios, e.g., when PET/CT is reported by low-experienced readers. Moreover, it increased the reader's confidence and the agreement among observers.

8-Aminoguanine and Its Actions on Renal Excretory Function.

BACKGROUND: The endogenous purine 8-aminoguanine induces diuresis/natriuresis/glucosuria by inhibiting PNPase (purine nucleoside phosphorylase); however, mechanistic details are unknown. METHODS: Here, we further explored in rats 8-aminoguanine's effects on renal excretory function by combining studies using intravenous 8-aminoguanine, intrarenal artery infusions of PNPase substrates (inosine and guanosine), renal microdialysis, mass spectrometry, selective adenosine receptor ligands, adenosine receptor knockout rats, laser doppler blood flow analysis, cultured renal microvascular smooth muscle cells, HEK293 cells expressing A2B receptors and homogeneous time resolved fluorescence assay for adenylyl cyclase activity. RESULTS: Intravenous 8-aminoguanine caused diuresis/natriuresis/glucosuria and increased renal microdialysate levels of inosine and guanosine. Intrarenal inosine, but not guanosine, exerted diuretic/natriuretic/glucosuric effects. In 8-aminoguanine-pretreated rats, intrarenal inosine did not induce additional diuresis/natriuresis/glucosuria. 8-Aminoguanine did not induce diuresis/natriuresis/glucosuria in A2B-receptor knockout rats, yet did so in A1- and A2A-receptor knockout rats. Inosine's effects on renal excretory function were abolished in A2B knockout rats. Intrarenal BAY 60-6583 (A2B agonist) induced diuresis/natriuresis/glucosuria and increased medullary blood flow. 8-Aminoguanine increased medullary blood flow, a response blocked by pharmacological inhibition of A2B, but not A2A, receptors. In HEK293 cells expressing A2B receptors, inosine activated adenylyl cyclase, and this was abolished by MRS 1754 (A2B antagonist). In renal microvascular smooth muscle cells, 8-aminoguanine and forodesine (PNPase inhibitor) increased inosine and 3',5'-cAMP; however, in cells from A2B knockout rats, 8-aminoguanine and forodesine did not augment 3',5'-cAMP yet increased inosine. CONCLUSIONS: 8-Aminoguanine induces diuresis/natriuresis/glucosuria by increasing renal interstitial levels of inosine which, via A2B receptor activation, increases renal excretory function, perhaps in part by increasing medullary blood flow.

Comparison of 18F-FDG PET/CT imaging with different dual time 18F-FDG PET/CT with forced diuresis in clinical diagnosis of prostate cancer.

The aim of this study was to compare the capability of different dual time (interval 1, 2, 3, or 4 hours) 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) with forced diuresis to diagnose prostate cancer (PCa). A retrospective review of 273 male patients from March 2009 to June 2019, with any focal 18F-FDG uptake in the prostate gland during PET/CT imaging. Early PET/CT imaging was performed 60 minutes after FDG injection. Delayed imaging was performed 1 to 4 hours after diuretic injection. For prostate lesions with increased 18F-FDG uptake, a spheroid-shaped volume of interest was drawn, including the entire lesion, and the maximum standard uptake value (SUVmax) of the lesion was measured. The SUVmax > 2.5 after delayed imaging and the retention index > 15% were used as the diagnostic criteria for PET/CT in the diagnosis of PCa. Otherwise, it was diagnosed as the benign prostate disease. The final diagnosis was based on histological examination, associated imaging studies, or/and clinical follow-up. The results of inter-group comparison showed that the SUVmax of 1-, 2-, 3-, and 4-hour delayed imaging after diuresis in PCa group was significantly higher than that in control group (P < .05), but there was no statistical difference in SUVmax of early imaging between PCa and control group (P > .05). And the retention index of PCa group that delayed 1, 2, 3, and 4 hours after diuresis were significantly higher than those of control group, respectively (P < .05). The diagnostic sensitivity of imaging delayed 1, 2, 3, and 4 hours after diuresis was 68.8%, 81.2%, 85.7 %, and 71.4%, the specificity was 52.5%, 74.5%, 70.6%, and 65.0%, and the accuracy was respectively 58.2%, 77.4%, 76.4%, and 67.6%, the positive predictive values were 44.0%, 68.9%, 64.3%, and 58.8%, and the negative predictive value were 75.6%, 85.4%, 88.9%, and 76.5%, respectively. 18F-FDG PET/CT imaging as an imaging tool lacks certain specificity in the diagnosis of PCa, regardless of whether the imaging is delayed. The main advantage of delayed diuretic imaging in PCa is that it can significantly improve the sensitivity, especially the diagnostic effect delayed 2 hours after diuresis is better.

[Evaluation of the results and feasibility of vibration, diuresis and inversion therapy in the treatment of upper urinary tract stones]. / Évaluation des résultats et de la faisabilité de la posturothérapie (hydratation, inversion, vibration) dans le traitement des calculs des voies urinaires supérieures.

OBJECTIVES: To evaluate the feasibility, efficiency, and predictive factors of therapeutic success of Vibration, Diuresis and Inversion (VDI) therapy for the removal of upper urinary tract stones. METHODS: It is a retrospective, single-center study at the CHU - La Conception, Marseille, France including all patients treated with VDI from 2013 to 2018. VDI was indicated for stones <6mm in first-line treatment or for residual fragments <6mm after ureteroscopy, PCNL, microPCNL. The protocol included 4 sessions in outpatient care from 2013 to 2015 then 6 sessions from 2015 to 2018 and a final radiological evaluation. RESULTS: In total, 109 patients or 489 sessions are reported: median age was 55 years [14-84], median BMI 25kg/m2 [15-37], average cumulative size of kidney stones 3mm ±4. VDI was performed after flexible ureteroscopy (62%), SWL (20%), percutaneous treatment (9%) or as a first-line treatment (9%). Compliance was 87 %. The median VAS during the session was 0[0-8]. The incidence of post-session renal colic was 4% (all Clavien I). The postoperative fragment-free and microfragment rates were respectively 39% and 21%, i.e. an overall success of 60% for kidney stones, and 43% and 21%, i.e. an overall success of 64% for lower pole kidney stones. CONCLUSION: VDI is a simple, non invasive and well tolerated technique for the elimination of small renal lithiasis after SWL, ureteroscopy, PCNL or as a first-line treatment.

Effect of water diuresis with hydrogen saturation on the course of acute kidney damage during the separation of oxidation and phosphorylation.

Molecular hydrogen has the ability to penetrate cells, easily reach mitochondria, overcome body barriers, penetrate areas of ischemia, edema and inflammation, improve energy supply by supplying additional electrons and have antioxidant and anti-inflammatory effects by neutralizing highly reactive hydroxyl radical and peroxynitrite. In this experiment, we included 60 nonlinear male rats weighing 0.16-0.18 kg and investigated the effect of a negative redox potential solution -297.3±5.27 mV with a molecular hydrogen saturation of 1.2 ppm on the functional-biochemical processes of the kidneys in tissue hypoxia in moderately resistant rats during the separation of oxidation and phosphorylation with the introduction of 2,4-dinitrophenol at a dose of 3 mg/kg. All studies were performed on moderately stable rats. Experimental, functional, biochemical, enzyme-linked immunosorbent, physicochemical, histoenzymochemical, and statistical research methods were used. Under conditions of renal hypoxia in the separation of oxidation and phosphorylation, the use of a solution of negative redox reabsorption of sodium ions in the distal nephron reduces the manifestations of tubular proteinuria, increases the activity of succinate dehydrogenase in the proximal nephron and reduces the redox potential of urine to negative values. Negative redox potential solution with molecular hydrogen saturation has a protective effect on the kidneys and reduces elevated levels of proinflammatory cytokines of tumor necrosis factor-α, interleukin-1-ß, and interleukin-6 in blood plasma, and causes oxidative modification of proteins in the renal cortex for their hypoxia in the separation of oxidation and phosphorylation.

Auto-diuresis Predicts Return of Bowel Function.

PURPOSE: Feeding a ventral hernia repair (VHR) patient before the return of bowel function (ROBF) can lead to distention and emesis. Many patients spontaneously diurese after surgery. We hypothesized that this auto-diuresis would signal ROBF. MATERIALS AND METHODS: A total of 395 patients who underwent open, laparoscopic, or mixed VHR were evaluated for correlation between fluid status and ROBF or discharge. ROBF within 24 hours and discharge within 24 hours or 48 hours were used as outcome measures. RESULTS: Patients remained an average 3.59 days after surgery in the hospital and the average ROBF was on day 2.99. The first shift of ≥700 mL of urine predicted ROBF ( P =0.03) and discharge ( P =0.04) within 24 hours. The first shift output of ≥500 mL predicted discharge within 48 hours ( P =0.02). CONCLUSION: Auto-diuresis after surgery is correlated to ROBF and discharge. Accurate fluid measurement can predict bowel function and allow early diet and discharge.

Impact of forced diuresis on retropulsion of disintegrated ureteral calculi during semi-rigid ureteroscopy: a double-blind randomized-controlled study.

The objective of this study is to assess the safety and efficacy of forced diuresis as an antiretropulsion strategy during the pneumatic disintegration of solitary lower ureteric stones with semi-rigid ureteroscopy (URS). A prospective randomized double-blind study was carried out from March 2019 to June 2021 for patients presented with unilateral solitary radiopaque lower ureteric stones ≤ 20 mm. Patients were randomized for URS into two groups, according to the use of forced diuresis using furosemide 1 mg/kg (GII) or not (GI). Perioperative parameters were compared between both groups, including retropulsion rate, stone-free rate (SFR), and need for auxiliary procedures and complications. A total of 148 patients were included; 72 (48.6%) in GI and 76 in the GII (51.4%), with respective stone size of 11.8 ± 2.6 vs.12.1 ± 2.4 mm. Both groups were comparable in demographic and baseline data, with a mean age of 47 ± 16 and 50 ± 14 years for GI and GII, respectively. GII had a significantly shorter disintegration time (10.5 ± 1.3 vs. 4.2 ± 2.1 min, p < 0.001), shorter operative time (33.1 ± 10.1 vs. 40.8 ± 9.1 min, p < 0.001), lower stone fragments migration rate during disintegration (6.5% vs. 18.1%, p = 0.04), lower retropulsion rate (1.3% vs. 11%, p = 0.02), higher SFR (96.1% vs. 86.1%, p = 0.04), and lower auxiliary procedures (3.9% vs. 13.8%, p = 0.03). Intraoperative and 6-h postoperative changes in heart rate and mean systolic blood pressure were comparable between both groups. Ephedrine injection (6-18 mg) was needed in significantly more GII patients (39.5% vs. 20.8%, p ≤ 0.01). It seems that forced diuresis during pneumatic lithotripsy of the lower ureteric stones is a safe and effective antiretropulsion technique. This would expand the alternative options to the antiretropulsion strategy, especially in centers where the laser and flexible ureteroscopes are not available.

Influence of intervention treatment by "heat-clearing and diuresis-promoting" prescription on NALP3, an inflammatory factor in acute gouty arthritis.

BACKGROUND: To investigate the efficacy of Qingre Lishi Decoction(QLRD), in the treatment of acute gouty arthritis, and its influence on the expression levels of inflammatory factor nucleotide-binding oligomerization domain-like receptor(NALP 3) in patients. METHODS: A total of 78 patients with acute gouty arthritis admitted to our hospital were randomly divided into the control group and the observation group, with 39 cases in each group. The control group was given basic treatment and colchicine tablets, and the observation group was given "heat-clearing and diuresis-promoting" prescription for intervention treatment. The main symptom score, treatment effective rate and laboratory indexes of the two groups were compared 7 days after treatment. RESULTS: After treatment, the scores of joint redness, hot pain, joint flexion and extension disorder, oliguria and constipation were improved in both groups, and the improvement degree in observation group was higher than that in control group (P < 0.05); the clinical effective rate in the observation group (94.87%) was higher than that in the control group (76.92%). The serum uric acid (UA), erythrocyte sedimentation rate (ESR), interleukin-1ß (IL-1ß) and NALP3 showed a decreasing trend, and the decrease degree of each index in observation group was higher than that in control group (P < 0.05). CONCLUSION: The "heat-clearing and diuresis-promoting" prescription for intervention treatment can effectively improve the clinical symptoms of patients with acute gouty arthritis and reduce the level of inflammatory factor NALP3, maintaining remarkable effect.

Chronic bladder catheterization for precise urine collection in awake mice.

Metabolic chambers are routinely used for urine collection in rodents. In mice, due to small urination volume, evaporation in the metabolic chambers (≈50%) distorts diuresis and urinalysis parameters. We have developed a new technique of bladder catheterization enabling long-term accurate and contamination-free urine collection in awake male and female mice for 30 days or longer. Daily diuresis in catheterized mice was twice higher as compared to metabolic cages. The twofold difference in urine recovery was preserved when the circadian variation of diuresis, the effects of furosemide, desmopressin and water load were estimated using the two techniques. Urine osmolarity, urinalysis, and microbiological parameters evidence higher quality of the catheter-collected urine. Using phenol red, we demonstrate utility of our technique for pharmacokinetic studies. 30 days after the surgery the catheters were patent and had minimal impact on the animals' heath. Bladder catheterization is a useful tool for physiological, pharmacological, and toxicological studies.

Postoperative aggressive diuresis prevents postoperative tissue edema and complications in patients undergoing distal pancreatectomy.

PURPOSE: Intraoperative fluid restriction is reported to be associated with reduced postoperative tissue edema and decreased incidence of postoperative pancreatic fistula (POPF) in pancreatic surgery. However, there is limited information regarding the postoperative approach to prevent postoperative tissue edema and reduce POPF. METHODS: Patients undergoing distal pancreatectomy from 2013 to 2018 in our institute were retrospectively enrolled (n = 128). The patients were classified into the two groups: an early diuresis group (ED group: patients administered diuretic agents on postoperative day 2 or earlier between 2016 and 2018, n = 69) and a conventional diuresis group (CD group: patients administered diuretic agents on postoperative day 3 or later between 2013 and 2015, n = 59). Postoperative tissue edema assessed by CT imaging and the incidence of clinically relevant POPF (CR-PF; grade B or C) were compared. RESULTS: Postoperative tissue edema was significantly reduced in the ED group (p < 0.0001). The incidence of CR-PF was lower in the ED group (19% vs. 32%, p = 0.082), especially in patients with postoperative diuresis on POD 1 (12%, p = 0.044). CONCLUSION: Early and aggressive postoperative diuresis potentially reduced postoperative visceral tissue edema. This postoperative approach to prevent tissue edema may reduce the incidence of CR-PF in pancreatic surgery.

Insights into the development of a new index, vesical adaptation response to diuresis, for understanding lower urinary tract dysfunction.

OBJECTIVES: To clarify how vesical adaptation response, the homeostatic system that constantly changes voided volume to adapt to diuresis, is involved in male lower urinary tract symptoms and bladder storage function. METHODS: We included male patients older than 65 years with lower urinary tract symptoms. Vesical adaptation response to diuresis was defined as a positive correlation between urine output rate and voided volume on 3-day sensory-related frequency volume charts. Patients were divided into two groups according to the presence or absence of vesical adaptation response to diuresis, and characteristics were compared between groups. RESULTS: Ninety-four male patients were finally analyzed. Vesical adaptation response to diuresis was found in 48 patients (51%) and was lacking in 46 patients (49%). Patients without vesical adaptation response to diuresis were significantly more often diagnosed with overactive bladder (P = 0.04). After adjusting for confounders, absence of vesical adaptation response to diuresis was significantly associated with overactive bladder (adjusted odds ratio 3.76, 95% confidence interval 1.34-10.55; P = 0.01) and benign prostatic enlargement (adjusted odds ratio 1.04, 95% confidence interval 1.01-1.07; P = 0.02). CONCLUSIONS: The absence of vesical adaptation response to diuresis, characterized by decreased voided volume during a diuretic phase, can be interpreted as a form of bladder storage dysfunction. Assessment of vesical adaptation response to diuresis may provide a new index of bladder storage function and contribute to a better understanding of the pathophysiology underlying bladder storage dysfunction in patients with lower urinary tract symptoms.

Comparación de métodos de diagnóstico para el tratamiento hemodinámico en recién nacidos y prematuros utilizando la medición de la vena cava, lactato y criterios clínicos / Comparison of diagnostic methods for hemodynamic treatment in unborn and pre-term infants using the measurement of vena cava, lactate, and clinical criteria

Introducción: no existe un criterio único para evaluar el estado hemodinámico de los recién nacidos y prematuros y las diferentes variables en el grupo de recién nacidos, como la edad gestacional, el peso al nacer y los períodos de nacimiento. Métodos: Se trata de un estudio observacional descriptivo, transversal, epidemiológico con dos cohortes de pacientes. Los recién nacidos a término y Pretérmino, atendidos en la Unidad de Neonatal del Hospital Pablo Arturo Suárez, participan durante los meses comprendidos entre Noviembre de 2019 a enero de 2020. Resultados: la medición ecográfica del flujo de la vena cava inferior (FVCI) es útil para el tratamiento de manejo del paciente neonatal hemodinámicamente inestable. La muestra estuvo conformada por 110 recién nacidos atendidos en el servicio de neonatología del Hospital Pablo Arturo Suárez desde noviembre de 2019 a enero de 2020. Quito, Pichincha, Ecuador. Las variables bajo peso al nacer y prematuridad moderada tienen un valor estadística-mente significativo para el uso de inotrópicos. Las demás variables no presentan valor esta-dísticamente significativo. La frecuencia cardíaca, el gasto urinario, la presión arterial media, el ácido láctico, el llenado capilar, el flujo de la vena cava superior y el flujo de la vena cava inferior tienen valores estadísticamente significativos. Las comparaciones de FVCI y superior (FVCS) con frecuencia cardíaca, gasto urinario, presión arterial media, ácido láctico, llenado capilar tienen un valor estadísticamente significativo, excepto para el llenado capilar >3 segundos en FCVI. Se utilizó el análisis multivariado de Componentes Principales Categóricos (CATPCA) para caracterizar el estado hemodinámico e inotrópico, que resultaron significativos en el análisis bivariado. Dimensión, uno de los gráficos bidimensionales, discrimina el uso o no de inotrópicos y las categorías de parámetros hemodinámicos TAM <35 mmHg, ácido láctico, llenado capilar, FVCI y FVCS. La dimensión dos discrimina entre las categorías de gasto urinario y FC. Conclusión: En recién nacidos a término y prematuros con bajo peso y adecuado peso al nacer con inestabilidad hemodinámica en general, que fueron evaluados con ecografía para medir el flujo de la vena cava, la concordancia entre los criterios clínicos y la valoración ecográfica del flujo fue de 0.4 cm / seg en ambos métodos. Esta situación significa que la medición de los flujos cava venosos por ecografía es útil para evaluar el estado hemodinámico de los pacientes neonatales.

Introduction: There is no single criterion available to assess the hemodynamic state of new-born in-fants and preterm infants and the different variables in the group of newborns, such as gestational age, birth weight, and periods of birth. Methods: This is an epidemiological, cross-sectional, descriptive observational study with two patient cohorts. Newborn-to-term and preterm neonates assisted at the Neonatal Unit of the Pablo Arturo Suarez Hospital participated during the months between November 2019 to January 2020. Results: Ultrasound measurement of the vena cava (FVC) flow is useful for the management treatment of hemodynamically unstable neonatal patients. The sample was made up of 110 newborns treated in the Pablo Arturo Suarez Hospital's neonatology service from November 2019 to January 2020. Quito, Pichincha, Ecuador. The variables low birth weight and moder-ate prematurity have a statistically sig-nificant value for inotropic use.The other variables do not present statistically significant values. Heart rate, urinary output, mean blood pressure, lactic acid, capillary filling, upper vena cava flow, and lower vena cava flow had statistically significant values. FVCI and FVCS comparisons with heart rate, urinary output, mean blood pressure, lactic acid, and capillary filling had statistically significant values, except for capil-lary filling >3 sec in FCVI. Multivariate analysis of categorical main components (CATPCA) was used to characterize the hemodynamic state and inotropic state, which were significant in the bivariate analysis. Dimension, one of the two-dimensional graphs, discriminates the use or not of inotropics and the categories of hemodynamic parameters TAM <35 mmHg, lactic acid, capillary filling, FVCI, and FVCS. Dimension IIdiscriminates between the categories of urinary expenditure and HR. Conclusion: In term and preterm infants with low weight and adequate birth weight with hemody-namic instability in general, who were evaluated with ultrasonography to measure the flow of the vena cava, the agreement between the clinical criteria and the ultrasound assessment of the flow was 0.4 cm/sec in both methods. This situation means that the measurement of venous cava flows by echo sonography is useful for assessing neonatal patients' hemodynamic status.

Role of Renal Sympathetic Nerves in GLP-1 (Glucagon-Like Peptide-1) Receptor Agonist Exendin-4-Mediated Diuresis and Natriuresis in Diet-Induced Obese Rats.

Background The gut-derived hormone GLP-1 (glucagon-like peptide-1) exerts beneficial effects against established risk factors for chronic kidney disease. GLP-1 influences renal function by stimulating diuresis and natriuresis and thus lowering arterial blood pressure. The role of the sympathetic nervous system has been implicated as an important link between obesity with elevated arterial pressure and chronic kidney disease. The primary aim of this study was to determine the contribution of renal sympathetic nerves on intrapelvic GLP-1-mediated diuresis and natriuresis in high-fat diet (HFD)-induced obese rats. Methods and Results Obesity was induced in rats by HFD for 12 weeks, followed by either surgical bilateral renal denervation or chronic subcutaneous endopeptidase neprilysin inhibition by sacubitril for a week. Diuretic and natriuretic responses to intrapelvic administration of the GLP-1R (GLP-1 receptor) agonist exendin-4 were monitored in anesthetized control and HFD rats. Renal GLP-1R expression and neprilysin expression and activity were measured. The effects of norepinephrine on the expression of GLP-1R and neprilysin in kidney epithelial LLC-PK1 cells were also examined. We found that diuretic and natriuretic responses to exendin-4 were significantly reduced in the HFD obese rats compared with the control rats (cumulative urine flow at 40 minutes, 387±32 versus 650±65 µL/gkw; cumulative sodium excretion at 40 minutes, 42±5 versus 75±10 µEq/gkw, P<0.05). These responses in the HFD rats were restored after ablation of renal nerves (cumulative urine flow at 40 minutes, 625±62 versus 387±32 µL/gkw; cumulative sodium excretion at 40 minutes, 70±9 versus 42±5 µEq/gkw, P<0.05). Renal denervation induced significant reductions in arterial pressure and heart rate responses to intrapelvic GLP-1 in the HFD rats. Renal denervation also significantly increased the GLP-1R expression and reduced neprilysin expression and activity in renal tissues from the HFD rats. Chronic subcutaneous neprilysin inhibition by sacubitril increased GLP-1-induced diuretic and natriuretic effects in the HFD rats. Finally, exposure of the renal epithelial cells to norepinephrine in vitro led to downregulation of GLP-1R expression but upregulation of neprilysin expression and activity. Conclusions These results suggest that renal sympathetic nerve activation contributes to the blunted diuretic and natriuretic effects of GLP-1 in HFD obese rats. This study provides significant novel insight into the potential renal nerve-neprilysin-GLP-1 pathway involved in renal dysfunction during obesity that leads to hypertension.

Balanced forced-diuresis compared to control as a reno-protective approach in cardiac surgery: secondary outcome of a randomized controlled trial, assessment of neutrophil gelatinase-associated lipocalin levels.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a recognised biomarker for acute kidney injury (AKI).This study investigated the impact of balanced forced-diuresis using RenalGuard® system (RG), in reducing acute kidney injury (AKI) rates and the associated NGAL levels (6-h post-CPB plasma level) post adult cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Patients included in the study were at high-risk for AKI post cardiac surgery, namely history of diabetes and/or anaemia, e-GFR 20-60 ml/min/1.73 m2, Logistic EuroScore > 5, anticipated CPB time > 120 min. Patients were randomized to either RG (n = 110) or managed as per current practice (control = 110). RIFLE-defined AKI rate (based on serum creatinine level increase) within first 3 days of surgery and 6-h post CPB NGAL levels were the primary and secondary end-points. RESULTS: Pre and intra-operative characteristics between the two groups were similar (p > 0.05) including the pre-op NGAL levels, the oxygen delivery (ecDO2i) and the carbon dioxide production (ecVCO2i) during CPB. Patients in the RG group had a significantly lower post-operative RIFLE-defined AKI rate compared to control (10% (11/110) v/s 20.9% (23/110), p = 0.03). Overall, median 6-h post CPB NGAL levels in patients with AKI were significantly higher than those who did not develop AKI (211 vs 150 ng/ml, p < 0.001). Patients managed by balanced forced-diuresis had lower post-operative NGAL levels (146 vs 178 ng/ml, p = 0.09). Using previously reported NGAL cut-off level for AKI (142 ng/ml), binary logistic regression analysis confirmed a beneficial effect of the RG system, with an increased risk of AKI of 2.2 times in the control group (OR 2.2, 95% CI 1.14-4.27, p = 0.02). CONCLUSIONS: Overall, the 6-h post-CPB plasma NGAL levels were significantly higher in patients who developed AKI. Patients managed with the novel approach of balanced forced-diuresis, provided by the RenalGuard® system, had a lower AKI rate and lower NGAL levels indicating a lesser degree of renal tissue injury. Trial registration ClinicalTrials.gov website, NCT02974946, https://clinicaltrials.gov/ct2/show/NCT02974946 .