FIRE Stones: impact of forced diuresis on the residual fragment rate after flexible ureteroscopy for destruction of kidney stones with laser-protocol for a randomized controlled two-parallel group multicenter trial with blinding evaluation.

BACKGROUND: Lithiasis is a common and recurrent disease. Flexible ureteroscopy (fURS) is the cornerstone of laser treatment of kidney stones. Kidney stones destruction requires its laser pulverization into small fragments in order to remove them through the ureter or improve their spontaneous expulsion along the urinary tract. However, most of the time, all the micro-fragments and dust created cannot be extracted using our surgical tools and may stay intra-renally at the end of the procedure. Adjuvant treatments (such as forced diuresis, inversion or mechanical pressure) were previously described to improve the expulsion of stone fragments after extra-corporeal shock wave lithotripsy. Nevertheless, the impact of adjuvant treatment after fURS remains unclear and mainly theoretical. OBJECTIVE: The primary objective is to show that the injection of 40 mg of furosemide in slow intravenous during 10 min, after the procedure, increases the stone-free rate 3 months after a fURS for destruction of kidney stones with laser. METHODS/DESIGN: The study will be a two-parallel group randomized, controlled, multicentric trial with a blinding evaluation. Nine French departments of urology will participate. Patients will be randomized in 2 groups: the experimental group (injection of 40 mg of furosemide at the end of the surgery) and a control one (usual care). Patients will be followed up for 3 months (± 2 weeks) after the surgery. Then, we will perform a low dose abdomino-pelvic CT scan. The primary outcome is the stone-free rate at 3 months. A centralized review of the images will be performed by two specialized radiologists, in a blind and crossed way to allow a homogenization of the results. The secondary outcomes will include the rate of early post-operative urinary tract infection (UTI), the evaluation of post-operative pain, and the safety of the use of furosemide in patients treated by fURS for renal stone laser destruction. As secondary objectives, it is also planned to look at the effect of the prescription of an alpha-blocker as usual treatment on stone-free rate and to assess the agreement between the imaging analysis of the urologist and the specialized radiologist. DISCUSSION: Lithiasis is a public health problem. It affects about 10% of the general population. This prevalence is increasing (multiplied by 3 in 40 years), partly due to changes in the population's eating habits over the years. The lithiasis patient is a patient with a chronic disease requiring annual follow-up and who may suffer from multiple recurrences, with a recurrence rate at 5 years of 50%. Recurrences are partly due to residual fragments left in the kidneys at the end of the operation. Other risk factors for recurrence include dietary hygiene and the presence of an associated metabolic disease. The metabolic blood and urine tests recommended by the Association Française d'Urologie (AFU) can be used to manage these last two problems. As far as residual fragments are concerned, their presence leads to an early recurrence of stones because they form the bed for a new aggregation of crystals in the kidneys. Being able to reduce the rate of residual fragments in patients with the use of furosemide at the end of the intervention therefore seems essential in the management of recurrences in our patients. This will also improve our patients' quality of life. Indeed, lithiasis disease leads to chronic pain associated with acute pain that motivates consultations to the emergency for specialized management. This study is the first to evaluate the impact of forced diuresis with the use of furosemide on the stone-free rate after a fURS for destruction of kidney stone with laser. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05916963 , first received: 22 June 2023. EU Clinical Trials Register EudraCT Number: 2022-502890-40-00.

Hypocitraturia as a biomarker of renal tubular acidosis in patients with Sjögren's disease.

INTRODUCTION: Sjögren's disease (SD) is an immune-mediated chronic inflammatory disease that affects epithelial tissues, mainly salivary and lacrimal glands. It also presents extraglandular manifestations. The main renal manifestation is tubulointerstitial nephritis (TIN), which can manifest as renal tubular acidosis (RTA). Urinary citrate may be a biomarker of RTA in these patients. The objective of this study was to evaluate whether hypocitraturia is a predictive biomarker of RTA in a sample of patients with SD in a tertiary hospital in southern Brazil. METHODS: All patients with SD who met the inclusion criteria and who participated in the rheumatology outpatient clinic of the Irmandade Santa Casa de Misericórdia de Porto Alegre were included. Demographic, SD, serological and urinary data were obtained. RTA was considered in those patients who persistently presented urinary pH above 5.5 and serum pH below 7.35. Patients who persistently had urinary pH above 5.5 underwent a urinary acidification test with furosemide and fludrocortisone. These patients received 1 mg of fludrocortisone and 40 mg of furosemide and had their urine samples tested 2, 4 and 6 h after taking the medications. The test was stopped at any urine sample with pH 5.5 or less. The variables were expressed as mean and standard deviation or interquartile range. The association between hypocitraturia and RTA was assessed using the chi-square. RESULTS: Forty-two patients were included, 95.2% female with a median age of 61.73 years. The prevalence of complete distal RTA was 4.88%. Twenty-eight patients underwent urine acidification testing. Five patients had hypocitraturia, and two of them had complete distal RTA. The association between hypocitraturia and RTA was statistically significant (p < 0.012), with a sensitivity of 100%, specificity of 91.2% and accuracy of 91.7%. The negative predictive value was 100%. The global renal assessment of the population demonstrated two patients with RTA, one patient with decreased renal function and six patients with proteinuria greater than 0.5 g/24 h. CONCLUSION: The prevalence of RTA in the studied population was 4.88%. Hypocitraturia had high sensitivity and accuracy for the diagnosis of RTA.

Intralesional combined digoxin and furosemide versus intralesional 5-flurouracil for the treatment of recalcitrant plantar warts: a prospective, randomized study.

There are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were observed to be effective and safe, however no comparison study between them was done. Our study was conducted to evaluate the efficacy of both therapies in the treatment of plantar warts. 90 adult patients with multiple recalcitrant plantar warts were included in our study. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated clinically and dermoscopically. Clinical response was reported in 24 patients (80%) of the combined digoxin and furosemide group with 40% complete response and in 24 patients (80%) of the 5-fluorouarcil group with 33.3% complete response. No statistically significant difference was observed between the two groups concerning efficacy and safety. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide are nearly equivalent in efficacy and safety for plantar wart treatment. Dermoscopy helps to take the truthful judgment about complete clearance of warts.

The acute effects of furosemide in acute heart failure assessed by remote dielectric sensing. A protocol.

INTRODUCTION: Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute heart failure (AHF). While the diuretic effect of loop diuretics is well established, it remains unclear how furosemide influences pulmonary congestion and cardiac filling pressures in the hyperacute phase before significant diuresis occurs. METHODS: This was a prospective study of adult patients with AHF and objective signs of pulmonary congestion admitted to the cardiac ward. Remote dielectric sensing (ReDS) will directly measure lung fluid content, and cardiac filling pressures will be assessed by echocardiography with Doppler and strain analysis. CONCLUSIONS: This study will examine if furosemide leads to a hyperacute reduction in pulmonary congestion assessed by ReDS independent of diuretic effects in patients with AHF. We hypothesise that the haemodynamic effect of furosemide shown on pulmonary congestion may explain the subjective instant relief in patients with AHF receiving furosemide. FUNDING: Dr. Grand's salary during this project is supported by a research grant from the Danish Cardiovascular Academy funded by Novo Nordisk Foundation grant number NNF20SA0067242 and by the Danish Heart Foundation. TRIAL REGISTRATION: This protocol was approved by the Scientific Ethical Committee, H-23029822, and the Danish Data Protection Agency P-2013-14703. The protocol was registered with ClinicalTrial.org on 29 August 2023 (Identifier: NCT06024889).

Hypocalcemia in the Immediate Postoperative Period Following Metabolic Bariatric Surgery - Hype or Harm?

PURPOSE: Hypocalcemia post-metabolic bariatric surgery (MBS) is a known long-term complication after hypoabsorptive procedures. However, data on immediate postoperative calcium are limited. Our aim was to evaluate the prevalence of hypocalcemia on the 1st postoperative day after MBS and correlate it with potential associated factors. MATERIALS AND METHODS: We analyzed data from all consecutive index MBS over 1 year. We collected data on demographics and on preoperative and postoperative values of serum calcium (TC), albumin, adjusted calcium (AC-Payne formula), magnesium, phosphorus, preoperative vitamin-D, and postoperative 24-h urine output, intravenous fluids (IVF), bolus intravenous furosemide, and creatine phosphokinase (CPK). Continuous data are expressed as means ± SD (range). Categorical data are presented as frequencies (%). Linear regression was implemented to designate potential correlations. RESULTS: The cohort included 86 patients (58.1% females). The mean preoperative TC was 9.4mg/dL ± 0.4 (8.5-10.5) and mean postoperative TC 7.8mg/dL ± 0.6 (6.3-9.3, 17.0% decrease). The mean preoperative AC was 10.1mg/dL ± 0.4 (9.2-11.2) and mean postoperative AC 8.5mg/dL ± 0.6 (7.0-10.0, 15.8% decrease). Seventy-three patients (84.8%) had abnormally low TC (< 8.5mg/dL), and 43 (50%) abnormally low AC. There was only weak correlation between postoperative TC and AC with magnesium (r = 0.258), phosphorus (r = 0.269), vitamin-D (-0.163), 24-h urine output (r = -0.168), IVF (r = -0.237), bolus furosemide (r = 0.155), and mean operative time (r = 0.010). CONCLUSIONS: In our cohort of patients, hypocalcemia was a real problem but we did not find any significant correlation with the examined factors. Further studies are warranted to validate our findings and investigate other potential correlations.

Evaluation of renal sodium handling in heart failure with preserved ejection fraction: A pilot study.

The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo-responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B-type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank-sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo-responsiveness to NPs.

Basal natriuresis as a predictor of diuretic resistance and clinical evolution in acute heart failure.

BACKGROUND: Some clinical guidelines recommend serial measurement of natriuresis to detect diuretic resistance (DR) in acute heart failure (AHF) patients, but it adds complexity to the management. OBJECTIVES: To correlate a single measurement of basal natriuresis (BN) on admission with the development of DR and clinical evolution in AHF hospitalized patients. METHODS: Prospective and multicenter study included AHF hospitalized patients, without shock or creatinine >2.5mg%. Patients received 40mg of intravenous furosemide on admission, then BN was measured, and diuretic treatment was guided by protocol. BN was considered low if <70 meq/L. DR was defined as the need of furosemide >240mg/day, tubular blockade (TB), hypertonic saline solution (HSS) or renal replacement therapy (RRT). In-hospital cardiovascular (CV) mortality, CV mortality and AHF readmissions at 60-day post-discharge were evaluated. RESULTS: 157 patients were included. BN was low in 22%. DR was development in 19% (12.7% furosemide >240mg/day, 8% TB, 4% RRT). Low NB was associated with DR (44% vs 12%; p 0.0001), persistence of congestion (26.5% vs 11.4%; p 0.05), furosemide >240 mg/day (29% vs 8%; p 0.003), higher cumulative furosemide dose at 72 hours (220 vs 160mg; p 0.0001), TB (20.6 vs 4.9%; p 0.008), RRT (11.8 vs 1.6%; p 0.02), worsening of AHF (27% vs 9%; p 0.01), inotropes use (21% vs 7%; p 0.48), respiratory assistance (12% vs 2%; p 0.02) and a higher in-hospital CV mortality (12% vs 4%; p 0.1). No association was demonstrated with post-discharge endpoints. CONCLUSIONS: In AHF patients, low BN was associated with DR, persistent congestion, need for aggressive decongestion strategies, and worse in-hospital evolution.

Comparison of preventive effects of combined furosemide and mannitol versus single diuretics, furosemide or mannitol, on cisplatin-induced nephrotoxicity.

Cisplatin (CDDP)-induced nephrotoxicity is a common dose-limiting toxicity, and diuretics are often administered to prevent nephrotoxicity. However, the efficacy and optimal administration of diuretics in preventing CDDP-induced nephrotoxicity remain to be established. This study aimed to evaluate the efficacy of combining furosemide and mannitol to prevent CDDP-induced nephrotoxicity. This was a post-hoc analysis of pooled data from a multicenter, retrospective, observational study, including 396 patients who received one or two diuretics for CDDP-based chemotherapy, compared using propensity score matching. Multivariate logistic regression analyses were used to identify risk factors for nephrotoxicity. There was no significant difference in the incidence of nephrotoxicity between the two groups (22.2% vs. 28.3%, P = 0.416). Hypertension, CDDP dose ≥ 75 mg/m2, and no magnesium supplementation were identified as risk factors for nephrotoxicity, whereas the use of diuretics was not found to be a risk factor. The combination of furosemide and mannitol showed no advantage over a single diuretic in preventing CDDP-induced nephrotoxicity. The renal function of patients receiving CDDP-based chemotherapy (≥ 75 mg/m2) and that of those with hypertension should be carefully monitored. Magnesium supplementation is important for these patients.

Development of pH-responsive Eudragit S100-functionalized silk fibroin nanoparticles as a prospective drug delivery system.

Silk fibroin nanoparticles (FNP) have been increasingly investigated in biomedical fields due to their biocompatibility and biodegradability properties. To widen the FNP versatility and applications, and to control the drug release from the FNP, this study developed the Eudragit S100-functionalized FNP (ES100-FNP) as a pH-responsive drug delivery system, by two distinct methods of co-condensation and adsorption, employing the zwitterionic furosemide as a model drug. The particles were characterized by sizes and zeta potentials (DLS method), morphology (electron microscopy), drug entrapment efficiency and release profiles (UV-Vis spectroscopy), and chemical structures (FT-IR, XRD, and DSC). The ES100-FNP possessed nano-sizes of ∼200-350 nm, zeta potentials of ∼ -20 mV, silk-II structures, enhanced thermo-stability, non-cytotoxic to the erythrocytes, and drug entrapment efficiencies of 30%-60%, dependent on the formulation processes. Interestingly, the co-condensation method yielded the smooth spherical particles, whereas the adsorption method resulted in durian-shaped ones due to furosemide re-crystallization. The ES100-FNP adsorbed furosemide via physical adsorption, followed Langmuir model and pseudo-second-order kinetics. In the simulated oral condition, the particles could protect the drug in the stomach (pH 1.2), and gradually released the drug in the intestine (pH 6.8). Remarkably, in different pH conditions of 6.8, 9.5, and 12, the ES100-FNP could control the furosemide release rates depending on the formulation methods. The ES100-FNP made by the co-condensation method was mainly controlled by the swelling and corrosion process of ES100, and followed the Korsmeyer-Peppas non-Fickian transport mechanism. Whereas, the ES100-FNP made by the adsorption method showed constant release rates, followed the zero-order kinetics, due to the gradual furosemide dissolution in the media. Conclusively, the ES100-FNP demonstrated high versatility as a pH-responsive drug delivery system for biomedical applications.

Fabrication and evaluation of stable amorphous polymer-drug composite particles via a nozzle-free ultrasonic nebulizer.

We present a promising method for producing amorphous drug particles using a nozzle-free ultrasonic nebulizer with polymers, specifically polyvinylpyrrolidone (PVP), poly(acrylic acid) (PAA), and Eudragit® S 100 (EUD). Model crystalline phase drugs-Empagliflozin, Furosemide, and Ilaprazole-are selected. This technique efficiently produces spherical polymer-drug composite particles and demonstrates enhanced stability against humidity and thermal conditions, compared to the drug-only amorphous particles. The composite particles exhibit improved water dissolution compared to the original crystalline drugs, indicating potential bioavailability enhancements. While there are challenges, including the need for continuous water supply for ultrasonic component cooling, dependency on the solubility of polymers and drugs in volatile organic solvents, and mildly elevated temperatures for solvent evaporation, our method offers significant advantages over traditional approaches. It provides a straightforward, flexible process adaptable to various drug-polymer combinations and consistently yields spherical amorphous solid dispersion (ASD) particles with a narrow size distribution. These attributes make our method a valuable advancement in pharmaceutical drug formulation and delivery.

Suppression of the TGF-ß signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice.

Transforming growth factor-ß (TGF-ß) signaling plays a significant role in multiple biological processes, including inflammation, immunity, and cell death. However, its specific impact on the cochlea remains unclear. In this study, we aimed to investigate the effects of TGF-ß signaling suppression on auditory function and cochlear pathology in mice with kanamycin-induced ototoxicity. Kanamycin and furosemide (KM-FS) were systemically administered to 8-week-old C57/BL6 mice, followed by immediate topical application of a TGF-ß receptor inhibitor (TGF-ßRI) onto the round window membrane. Results showed significant TGF-ß receptor upregulation in spiral ganglion neurons (SGNs) after KM-FA ototoxicity, whereas expression levels in the TGF-ßRI treated group remained unchanged. Interestingly, despite no significant change in cochlear TGF-ß expression after KM-FS ototoxicity, TGF-ßRI treatment resulted in a significant decrease in TGF-ß signaling. Regarding auditory function, TGF-ßRI treatment offered no therapeutic effects on hearing thresholds and hair cell survival following KM-FS ototoxicity. However, SGN loss and macrophage infiltration were significantly increased with TGF-ßRI treatment. These results imply that inhibition of TGF-ß signaling after KM-FS ototoxicity promotes cochlear inflammation and SGN degeneration.

Serial direct sodium removal in patients with heart failure and diuretic resistance.

AIMS: Loop diuretics may exacerbate cardiorenal syndrome (CRS) in heart failure (HF). Direct sodium removal (DSR) using the peritoneal membrane, in conjunction with complete diuretic withdrawal, may improve CRS and diuretic resistance. METHODS AND RESULTS: Patients with HF requiring high-dose loop diuretics were enrolled in two prospective, single-arm studies: RED DESERT (n = 8 euvolaemic patients), and SAHARA (n = 10 hypervolaemic patients). Loop diuretics were withdrawn, and serial DSR was utilized to achieve and maintain euvolaemia. At baseline, participants required a median 240 mg (interquartile range [IQR] 200-400) oral furosemide equivalents/day, which was withdrawn in all participants during DSR (median time of DSR 4 weeks [IQR 4-6]). Diuretic response (queried by formal 40 mg intravenous furosemide challenge and 6 h urine sodium quantification) increased substantially from baseline (81 ± 37 mmol) to end of DSR (223 ± 71 mmol, p < 0.001). Median time to re-initiate diuretics was 87 days, and the median re-initiation dose was 8% (IQR 6-10%) of baseline. At 1 year, diuretic dose remained substantially below baseline (30 [IQR 7.5-40] mg furosemide equivalents/day). Multiple dimensions of kidney function such as filtration, uraemic toxin excretion, kidney injury, and electrolyte handling improved (p < 0.05 for all). HF-related biomarkers including N-terminal pro-B-type natriuretic peptide, carbohydrate antigen-125, soluble ST2, interleukin-6, and growth differentiation factor-15 (p < 0.003 for all) also improved. CONCLUSIONS: In patients with HF and diuretic resistance, serial DSR therapy with loop diuretic withdrawal was feasible and associated with substantial and persistent improvement in diuretic resistance and several cardiorenal parameters. If replicated in randomized controlled studies, DSR may represent a novel therapy for diuretic resistance and CRS. CLINICAL TRIAL REGISTRATION: RED DESERT (NCT04116034), SAHARA (NCT04882358).

Impact of baseline kidney dysfunction on oral diuretic efficacy following hospitalization for heart failure - insights from TRANSFORM-HF.

AIM: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all-cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half-life, but direct supportive evidence is lacking. METHODS AND RESULTS: The TRANSFORM-HF trial randomized patients hospitalized for HF to a long-term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post-hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30-<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30-<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all-cause mortality and all-cause (re)-hospitalizations, both when assessing eGFR categorically or continuously (p-value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ-CSS (p-value for interaction all >0.052) when assessing eGFR categorically or continuously. CONCLUSION: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient-reported outcomes between torsemide and furosemide, irrespective of renal function.

Furosemide Derails Human Lysozyme Fibrillation by Interacting with Aggregation Hot Spots: A Biophysical Comprehension.

Kidney-associated human lysozyme amyloidosis leads to renal impairments;thus, patients are often prescribed furosemide. Based on this fact, the effect of furosemide on induced human lysozyme fibrillation, in vitro, is evaluated by spectroscopic, calorimetric, computational, and cellular-based assays/methods. Results show that furosemide increases the lag phase and decreases the apparent rate of aggregation of human lysozyme, thereby decelerating the nucleation phase and amyloid fibril formation, as confirmed by the decrease in the level of Thioflavin-T fluorescence. Fewer entities of hydrodynamic radii of ∼171 nm instead of amyloid fibrils (∼412 nm) are detected in human lysozyme in the presence of furosemide by dynamic light scattering. Moreover, furosemide decreases the extent of conversion of the α/ß structure of human lysozyme into a predominant ß-sheet. The isothermal titration calorimetry established that furosemide forms a complex with human lysozyme, which was also confirmed through fluorescence quenching and computational studies. Also, human lysozyme lytic activity is inhibited competitively by furosemide due to the involvement of amino acid residues of the active site in catalysis, as well as complex formation. Conclusively, furosemide interacts with Gln58, Ile59, Asn60, Ala108, and Trp109 of aggregation-prone regions 2 and 4 of human lysozyme, thereby masking its sites of aggregation and generating only lower-order entities that are less toxic to red blood cells than the fibrils. Thus, furosemide slows the progression of amyloid fibrillation in human lysozyme.

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.

Prospective assessment of the impact of intraoperative diuretics in kidney transplant recipient surgery.

BACKGROUND: The use of intraoperative diuretics, such as furosemide or mannitol, during kidney transplantation has been suggested to reduce the rate of delayed graft function (DGF). The evidence base for this is sparse, however, and there is substantial variation in practice. We sought to evaluate whether the use of intraoperative diuretics during kidney transplantation translated into a reduction in DGF. METHODS: We conducted a cohort study evaluating the use of furosemide or mannitol given intraoperatively before kidney reperfusion compared with control (no diuretic). Adult patients receiving a kidney transplant for end-stage renal disease were allocated to receive furosemide, mannitol, or no diuretic. The primary outcome was DGF; secondary outcomes were graft function at 30 days and perioperative changes in potassium levels. Descriptive and comparative statistics were used where appropriate. RESULTS: A total of 162 patients who received a kidney transplant from a deceased donor (either donation after neurologic determination of death or donation after circulatory death) were included over a 2-year period, with no significant between-group differences. There was no significant difference in DGF rates between the furosemide, mannitol, and control groups. When the furosemide and mannitol groups were pooled (any diuretic use) and compared with the control group, however, there was a significant improvement in the odds that patients would be free of DGF (odds ratio 2.10, 95% confidence interval 1.06-4.16, 26% v. 44%, p = 0.03). There were no significant differences noted in any secondary outcomes. CONCLUSION: This study suggests the use of an intraoperative diuretic (furosemide or mannitol) may result in a reduction in DGF in patients undergoing kidney transplantation. Further study in the form of a randomized controlled trial is warranted.

Urinary Cell Cycle Arrest Biomarkers and Diuretic Efficiency in Acute Heart Failure.

INTRODUCTION: This study aimed to evaluate the association between the NephroCheck® test AKIRisk® score, diuretic efficiency (DE), and the odds of worsening kidney function (WKF) within the first 72 h of admission in patients hospitalized for acute heart failure (AHF). METHODS: The study prospectively enrolled 125 patients admitted with AHF. NephroCheck® test was obtained within the first 24 h of admission. DE was defined as net fluid urine output per 40 mg of furosemide equivalents. RESULTS: The median AKIRisk® score was 0.11 (IQR 0.06-0.34), and 38 (30.4%) patients had an AKIRisk® score >0.3. The median cumulative DE at 72 h was 1,963 mL (IQR 1317-3,239 mL). At 72 h, a total of 10 (8%) patients developed an absolute increase in sCr ≥0.5 mg/dL (WKF). In a multivariable setting, there was an inverse association between the AKIRisk® score and DE within the first 72 h. In fact, the highest the AKIRisk® score (centered at 0.3), the higher the likelihood of poor DE (below the median) and WKF at 72 h (odds ratio [OR] 2.04; 95%; CI: 1.02-4.07; p = 0.043, and OR 3.31, 95% CI: 1.30-8.43; p = 0.012, respectively). CONCLUSION: In patients with AHF, a higher NephroCheck® AKIRisk® score is associated with poorer DE and a higher risk of WKF at 72 h. Further research is needed to confirm the role of urinary cell cycle arrest biomarkers in the AHF scenario.

Furosemide to lower antenatal severe hypertension: a randomized placebo-controlled trial.

BACKGROUND: Hypertensive disorders of pregnancy are a leading cause of perinatal morbidity, and timely treatment of severely elevated blood pressure is recommended to prevent serious sequelae. In acute hypertension marked by increased blood volume, it is unknown whether diuretics used as an adjunct to antihypertensive medications lead to more effective blood pressure control. OBJECTIVE: This study aimed to evaluate whether the addition of intravenous furosemide to first-line antihypertensive agents reduces systolic blood pressure in acute-onset, severe antenatal hypertension with wide (≥60 mm Hg) pulse pressure. STUDY DESIGN: In this double-blinded randomized trial, participants received 40 mg of intravenous furosemide or placebo in addition to a first-line antihypertensive agent. The primary outcome was mean systolic blood pressure during the first hour after intervention. Secondary outcomes included corresponding diastolic blood pressure; systolic blood pressure, diastolic blood pressure, and pulse pressure at 2 hours after intervention; total reduction from qualifying blood pressure; duration of blood pressure control; need for additional antihypertensive doses within 1 hour; and electrolytes and urine output. A sample size of 35 participants per group was planned to detect a 15-mm Hg difference in blood pressure. RESULTS: Between January 2021 and March 2022, 65 individuals were randomized: 33 to furosemide and 32 to placebo. Baseline characteristics were similar between the groups. There was no difference in the primary outcome of mean 1-hour systolic blood pressure (147 [14.8] vs 152 [13.8] mm Hg; P=.200). We found a reduction in 2-hour systolic blood pressure (139 [18.5] vs 154 [18.4] mm Hg; P=.007) and a decrease in 2-hour pulse pressure (55 [12.5] vs 67 [15.1]; P=.003) in the furosemide group. Subgroup analysis according to hypertension type showed a significant reduction in 2-hour systolic blood pressure and 2-hour pulse pressure among patients with new-onset hypertension, but not among those with preexisting hypertension. Urine output was greater in the furosemide group, with no difference in electrolytes and creatinine before and after intervention. CONCLUSION: Intravenous furosemide in conjunction with a first-line antihypertensive agent did not significantly reduce systolic blood pressure in the first hour after administration. However, both systolic blood pressure and pulse pressure at 2 hours were decreased in the furosemide group. These findings suggest that a 1-time dose of intravenous furosemide is a reasonable adjunct to achieve blood pressure control, particularly in patients in whom increased volume is suspected.

Diuretic use and outcomes in patients with heart failure with reduced ejection fraction: Insights from the VICTORIA trial.

AIMS: In VICTORIA, vericiguat compared with placebo reduced the risk of cardiovascular death (CVD) and heart failure hospitalization (HFH) in patients enrolled after a worsening heart failure (WHF) event. We examined clinical outcomes and efficacy of vericiguat as it relates to background use of loop diuretics in patients with WHF. METHODS AND RESULTS: We calculated the total daily loop diuretic dose equivalent to furosemide dosing at randomization and categorized these as: no loop diuretic, 1-39, 41-80, 40, and >80 mg total daily dose (TDD). The primary composite outcome of CVD/HFH and its components were evaluated based on TDD loop diuretic and expressed as adjusted hazard ratios with 95% confidence intervals. Post-randomization rates of change in TDD were also examined. Of 4974 patients (98% of the trial) with diuretic dose information available at randomization, 540 (10.8%) were on no loop diuretic, 647 (13.0%) were on 1-39, 1633 (32.8%) were on 40, 1185 (23.8%) were on 41-80, and 969 (19.4%) were on >80 mg TDD. Patients with higher TDD had a higher rate of primary and secondary clinical outcomes. There were no significant interactions with TDD at randomization and efficacy of vericiguat versus placebo for any outcome (all pinteraction > 0.5). Post-randomization diuretic dose changes for vericiguat and placebo showed similar rates of up-titration (19.6 and 20.2/100 person-years), down-titration (16.8 and 18.1/100 person-years), and stopping diuretics (22.9 and 24.2/100 person-years). CONCLUSIONS: Loop diuretic TDD at randomization was independently associated with worse outcomes in this high-risk population. The efficacy of vericiguat was consistent across the range of diuretic doses.

Loop diuretic down-titration at discharge in patients hospitalized for acute heart failure.

AIMS: The current literature provides limited guidance on the best diuretic strategy post-hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes. METHODS AND RESULTS: It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down-titration group and (ii) the stable/up-titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all-cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78-92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down-titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86-2.06, P = 0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125. CONCLUSIONS: In patients hospitalized for AHF, furosemide down-titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down-titration on the outcome. In patients with severe congestion or residual congestion at discharge, down-titration was associated with an increased risk of mortality and/or heart failure readmission.