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Effect of furosemide on body composition and urinary proteins that mediate tubular sodium and sodium transport-A randomized controlled trial.
Mose, FH, Oczachowska-Kulik, AE, Fenton, RA, Bech, JN
Physiological reports. 2021;(24):e14653
Abstract
BACKGROUND Furosemide inhibits the sodium potassium chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle and increases urinary water and sodium excretion. This study investigates the effect of furosemide on body composition estimated with multifrequency bioimpedance spectroscopy (BIS) technique and urinary proteins from NKCC2. METHODS This study is a randomized, placebo-controlled, crossover study where healthy subjects received either placebo or 40 mg furosemide on two separate occasions, where body composition with BIS, renal function, proteins from tubular proteins that mediate sodium and water transport, and plasma concentrations of vasoactive hormones were measured before and after intervention. RESULTS We observed an expected increased diuresis with a subsequent reduction in bodyweight of (-1.51 ± 0.36 kg, p < .001) and extracellular water (ECW; -1.14 ± 0.23 L, p < .001) after furosemide. We found a positive correlation between the decrease in ECW and a decrease in bodyweight and a negative correlation between the decrease in ECW and the increase in urinary output. Intracellular water (ICW) increased (0.47 ± 0.28 L, p < .001). Urinary excretion of NKCC2 increased after furosemide and the increase in NKCC2 correlated with an increase in urine output and a decrease in ECW. CONCLUSION We found BIS can detect acute changes in body water content but the method may be limited to estimation of ECW. BIS demonstrated that furosemide increases ICW which might be explained by an extracellular sodium loss. Finally, urinary proteins from NKCC2 increases after furosemide with a good correlation with diuresis end the decrease in ECW.
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Diuretic therapy as prognostic enrichment factor for clinical trials in patients with heart failure with reduced ejection fraction.
Coiro, S, Girerd, N, McMurray, JJV, Pitt, B, Swedberg, K, van Veldhuisen, DJ, Lamiral, Z, Rossignol, P, Zannad, F
Clinical research in cardiology : official journal of the German Cardiac Society. 2021;(8):1308-1320
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Abstract
BACKGROUND Loop diuretics are the mainstay of congestion treatment in patients with heart failure (HF). We assessed the association between baseline loop diuretic use and outcome. We also compared the increment in risk related to diuretic dose with conventional prognostic enrichment criteria used in the EMPHASIS-HF trial, which included patients with systolic HF and mild symptoms, such as prior hospitalization and elevated natriuretic peptides. METHODS Individual analyses were performed according to baseline loop diuretic usage (furosemide-equivalent dose > 40 mg, 1-40 mg, and no furosemide), and according to enrichment criteria adopted in the trial [i.e. recent hospitalization (< 30 days or 30 to 180 days prior to randomization) due to HF or other cardiovascular cause, or elevated natriuretic peptides]. The primary endpoint was a composite of cardiovascular death or HF hospitalization. RESULTS Loop diuretic usage at baseline (HR for > 40 mg furosemide-equivalent dose = 3.16, 95% CI 2.43-4.11; HR for 1-40 mg = 2.06, 95% CI 1.60-2.65) was significantly associated with a higher risk for the primary endpoint in a stepwise manner when compared to no baseline loop diuretic usage. In contrast, the differences in outcome rates were more modest when using history of hospitalization and/or BNP: all HR ranged from 1 (reference, non-HF related CV hospitalization > 30 days) to 2.04 (HF hospitalization < 30 days). The effect of eplerenone on the primary endpoint was consistent across subgroups in both analyses (P for interaction ≥ 0.2 for all). CONCLUSIONS Loop diuretic usage (especially at doses > 40 mg) identified patients at higher risk than history of HF hospitalization and/or high BNP blood concentrations.
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Early short-course corticosteroids and furosemide combination to treat non-critically ill COVID-19 patients: An observational cohort study.
Kevorkian, JP, Riveline, JP, Vandiedonck, C, Girard, D, Galland, J, Féron, F, Gautier, JF, Mégarbane, B
The Journal of infection. 2021;(1):e22-e24
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Randomized study comparing mannitol with furosemide for the prevention of cisplatin-induced renal toxicity in non-small cell lung cancer: The OLCSG1406 trial.
Makimoto, G, Hotta, K, Oze, I, Ninomiya, K, Nakanishi, M, Hara, N, Kano, H, Watanabe, H, Hata, Y, Nishii, K, et al
Asia-Pacific journal of clinical oncology. 2021;(1):101-108
Abstract
AIM: Evidence is lacking on the best standard method for forced diuresis to prevent cisplatin-induced nephrotoxicity. We compared the cisplatin-induced nephrotoxicity prevention effect of furosemide or mannitol in patients with advanced non-small cell lung cancer. METHODS Patients with advanced non-small cell lung cancer suitable to receive cisplatin-containing regimen were randomly assigned to receive furosemide or mannitol with appropriate hydration. The primary endpoint was the proportion of ≥ grade 1 serum creatinine elevation in the first cycle. RESULTS The trial was terminated early with 44 (22 per arm) of the planned 66 patients because of slow accrual. Patients' characteristics were well balanced with median baseline creatinine clearance of 98.0 and 95.1 mL/min in the furosemide and mannitol arms, respectively. In the first cycle, two (9%) and four (18%) patients developed grade 1 creatinine elevation (P = .66), respectively, despite no ≥ grade 2 toxicity. The median times to develop the worst creatinine score were 10 and 8 days, respectively. For all cycles, median times to recover to grade 0 were 56 and 20 days, respectively. The furosemide arm was characterized by relatively high urine output after cisplatin administration (900 vs 550 mL/h), low frequency of unplanned additional hydration (14% vs 32%), and high incidence of hyponatremia (18% and 5%) compared with the mannitol arm. Both arms showed similar progression-free survival and overall survival. CONCLUSION The preventive effect of the two forced diuretics on cisplatin-induced nephrotoxicity was not significantly different. However, the two diuretics have some distinct types of clinical presentations.
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Simultaneous Use of Hypertonic Saline and IV Furosemide for Fluid Overload: A Systematic Review and Meta-Analysis.
Liu, C, Peng, Z, Gao, X, Gajic, O, Dong, Y, Prokop, LJ, Murad, MH, Kashani, KB, Domecq, JP
Critical care medicine. 2021;(11):e1163-e1175
Abstract
OBJECTIVES To evaluate the efficacy of the simultaneous hypertonic saline solution and IV furosemide (HSS+Fx) for patients with fluid overload compared with IV furosemide alone (Fx). DATA SOURCES Electronic databases (MEDLINE, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, PsycINFO, Scopus, and WOS) were searched from inception to March 2020. STUDY SELECTION Randomized controlled trials on the use of HSS+Fx in adult patients with fluid overload versus Fx were included. DATA EXTRACTION Data were collected on all-cause mortality, hospital length of stay, heart failure-related readmission, along with inpatient weight loss, change of daily diuresis, serum creatinine, and 24-hour urine sodium excretion from prior to post intervention. Pooled analysis with random effects models yielded relative risk or mean difference with 95% CIs. DATA SYNTHESIS Eleven randomized controlled trials comprising 2,987 acute decompensated heart failure patients were included. Meta-analysis demonstrated that HSS+Fx was associated with lower all-cause mortality (relative risk, 0.55; 95% CI, 0.46-0.67; p < 0.05; I2 = 12%) and heart failure-related readmissions (relative risk, 0.50; 95% CI, 0.33-0.76; p < 0.05; I2 = 61%), shorter hospital length of stay (mean difference, -3.28 d; 95% CI, -4.14 to -2.43; p < 0.05; I2 = 93%), increased daily diuresis (mean difference, 583.87 mL; 95% CI, 504.92-662.81; p < 0.05; I2 = 76%), weight loss (mean difference, -1.76 kg; 95% CI, -2.52 to -1.00; p < 0.05; I2 = 57%), serum sodium change (mean difference, 6.89 mEq/L; 95% CI, 4.98-8.79; p < 0.05; I2 = 95%), and higher 24-hour urine sodium excretion (mean difference, 61.10 mEq; 95% CI, 51.47-70.73; p < 0.05; I2 = 95%), along with decreased serum creatinine (mean difference, -0.46 mg/dL; 95% CI, -0.51 to -0.41; p < 0.05; I2 = 89%) when compared with Fx. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from low to moderate. CONCLUSIONS Benefits of the HSS+Fx over Fx were observed across all examined outcomes in acute decompensated heart failure patients with fluid overload. There is at least moderate certainty that HSS+Fx is associated with a reduction in mortality in patients with acute decompensated heart failure. Factors associated with a successful HSS+Fx utilization are still unknown. Current evidence cannot be extrapolated to other than fluid overload states in acute decompensated heart failure.
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Comparative effectiveness of furosemide vs torasemide in symptomatic therapy in heart failure patients: A randomized controlled study protocol.
Li, Y, Li, L, Guo, Z, Zhang, S
Medicine. 2021;(7):e24661
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BACKGROUND We performed this randomized controlled study protocol to investigate the efficacy and adverse effects of furosemide vs torasemide in patients with heart failure (HF). METHOD The present study was authorized by the local research ethics committee of Shanxi Cardiovascular Hospital (no. 48736645) and informed consent was obtained from all patients. Patients were enrolled in a consecutive prospective manner on a voluntary basis. Patients who were aged 18 years and older with HF who were eligible to enroll in this randomized trial. All patients had evidence of left ventricular systolic dysfunction, confirmed by echocardiographic or nuclear imaging. The exclusion criteria were left ventricular diastolic dysfunction only, or receipt of medical or pharmaceutical care in other health systems. The primary efficacy end point was the change in procollagen type I carboxyterminal peptide (PICP) serum levels between baseline and final visit. Secondary efficacy variables included parameters related to the clinical course of HF, such as body weight, presence of edema, signs and symptoms of HF, electrocardiogram and echocardiographic evaluation, amino-terminal pro brain-type natriuretic peptide (NT-proBNP) serum levels measured by ELISA method, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, and renal function. RESULTS One hundred patients who met the inclusion criteria were included in our study, Table 1 showed the effects of furosemide and torsemide on measures of clinical outcomes. DISCUSSION Fluid overload is the primary cause of hospitalization among patients with HF. Preventing circulatory congestion requires careful control of dietary sodium and chronic administration of loop diuretics. Torasemide and furosemide are representatives of loop diuretics with an identical diuretic mechanism, but different pharmacokinetic properties and additional effects. There is a need for reliable conclusion regarding the comparison of furosemide and torasemide in patients with HF. Several limitation should be noted: 1. the small number of participants did not enable assessment of the impact of torasemide and furosemide in different clinically relevant subgroups that is, elderly, patients with chronic kidney disease, dilated cardiomyopathy; 2. short-term follow up might lead to underestimation of the complications; 3. methodological weakness in study design may affect the results. Future high quality studies were still required.
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Meta-analysis of the effects of furosemide combined with hydration therapy on contrast-induced acute kidney injury after coronary intervention.
Hu, MJ, Luo, EF, Tang, CC, Wang, L, Zhang, QG, Gong, JB
European review for medical and pharmacological sciences. 2021;(14):4729-4737
Abstract
OBJECTIVE A meta-analysis was performed to evaluate the effect of furosemide combined with hydration therapy on the incidence and prognosis of contrast-induced acute kidney injury (CI-AKI) in patients after coronary intervention. MATERIALS AND METHODS Through the PubMed, EMBASE, Cochrane Library and Web of Science databases, all relevant literature from database establishment until October 1, 2020, was retrieved and screened. Quality evaluation was performed using the risk of bias evaluation tool recommended by the Cochrane Collaboration network, data extraction was performed based on pre-selected effect indicators, and statistics were calculated using Review Manager 5.3 analysis software. RESULTS A total of 2084 patients in 9 studies were included in the meta-analysis. The results showed that furosemide combined with hydrotherapy had no effect on the incidence of CI-AKI (OR = 0.85, 95% CI [0.46, 1.60], p = 0.62) and can significantly decrease the incidence of major adverse cardiovascular events (MACEs) (OR = 0.43, 95% CI [0.27, 0.67], p = 0.0003) and mortality (OR = 0.24, 95% CI [0.08, 0.79], p = 0.02) in patients. However, it had no significant impact on the need for postoperative dialysis treatment, postoperative creatinine level or length of hospital stay. CONCLUSIONS Furosemide combined with hydration therapy has no significant effect on the incidence of CI-AKI in patients after coronary intervention but can reduce the incidence of MACEs and mortality, thereby providing clinical benefits.
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Efficacy and safety of intermittent vs continuous furosemide for heart failure concomitant renal dysfunction: A protocol for systematic review and meta-analysis.
Chen, S, Lin, Y, Zhou, M, Zhou, C
Medicine. 2021;(16):e25669
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BACKGROUND Currently, there are no meta-analyses evaluating the efficacy and safety of intermittent vs continuous furosemide for heart failure concomitant renal dysfunction. Our protocol is conceived to evaluate the efficacy and safety of intermittent vs continuous furosemide for heart failure concomitant renal dysfunction. METHODS We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines and the recommendations of the Cochrane Collaboration to conduct this meta-analysis. The systematic review protocol has been registered in Open Science Framework registries. The following databases including PubMed, Cochrane Library, Web of Science, and EMBASE will be searched using the key phrases "loop diuretics," "furosemide," "heart failure," and "renal dysfunction" for all randomized clinical trials (RCTs) published up to May 2021. Revman 5.3 (Nordic Cochrane Centre, Denmark) will be used to complete the meta-analysis and generate forest plots. We will choose between a fixed effects and random effects model based upon the heterogeneity of included studies. Significance will be set at P < .05. RESULTS Our protocol is conceived to test the hypothesis that continuous furosemide could lead to better outcomes in patients presenting with heart failure concomitant renal dysfunction. REGISTRATION NUMBER 10.17605/OSF.IO/CQZRS.
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Chronic kidney disease progression in patients with resistant hypertension subject to 2 therapeutic strategies: Intensification with loop diuretics vs aldosterone antagonists.
Verdalles, U, Goicoechea, M, García de Vinuesa, S, Torres, E, Hernández, A, Verde, E, Pérez de José, A, Luño, J
Nefrologia. 2020;(1):65-73
Abstract
INTRODUCTION Actualy, there are few data about glomerular filtration rate (eGFR) drop in patients with resistant hypertension and how diferent therapies can modify chronic kidney disease progression (CKD). OBJECTIVE To evaluate CKD progression in patients with resistant hypertension undergoing 2diferent therapies: treatment with spironolactone or furosemide. METHODS We included 30 patients (21M, 9W) with a mean age of 66.3±9.1 years, eGFR 55.8±16.5ml/min/1.73 m2, SBP 162.8±8.2 and DBP 90.2±6.2mmHg: 15 patients received spironolactone and 15 furosemide and we followed up them a median of 32 months (28-41). RESULTS The mean annual eGFR decrease was -2.8±5.4ml/min/1.73 m2. In spironolactone group was -2.1±4.8ml/min/1.73 m2 and in furosemide group was -3.2±5.6ml/min/1.73 m2, P<0.01. In patients received spironolactone, SBP decreased 23±9mmHg and in furosemide group decreased 16±3mmHg, P<.01. DBP decreased 10±8mmHg and 6±2mmHg, respectively (P<.01). Treatment with spironolactone reduced albuminuria from a serum albumin/creatine ratio of 210 (121-385) mg/g to 65 (45-120) mg/g at the end of follow-up, P<.01. There were no significant changes in the albumin/creatinine ratio in the furosemide group. The slower drop in kidney function was associated with lower SBP (P=.04), higher GFR (P=.01), lower albuminuria (P=.01), not diabetes mellitus (P=.01) and treatment with spironolactone (P=.02). Treatment with spironolactone (OR 2.13, IC 1.89-2.29) and lower albuminuria (OR 0.98, CI 0.97-0.99) maintain their independent predictive power in a multivariate model. CONCLUSION Treatment with spironolactone is more effective reducing BP and albuminuria in patients with resistant hypertension compared with furosemide and it is associated with a slower progression of CKD in the long term follow up.
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Higher Diuretic Requirements in Acute Heart Failure With Admission Hyponatraemia Versus Normonatraemia.
Omar, HR, Guglin, M
Heart, lung & circulation. 2020;(2):233-241
Abstract
BACKGROUND Diuretic requirements in patients with acute decompensated heart failure (ADHF) and hyponatraemia versus normonatraemia on admission has not been previously explored. METHODS The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial dataset was utilised to examine the characteristics and diuretic requirements of patients with ADHF with hyponatraemia or normonatraemia on admission. RESULTS Patients with ADHF and admission hyponatraemia (n = 103, average Na 130.2 meq/L) had a higher degree of congestion evident in higher frequency of jugular venous distension (JVD) >12 cmH2O (p = 0.007), 2+ lower extremity oedema (p = 0.001), and higher right atrial pressure (p = 0.007), compared with normonatraemic patients (n = 327, average Na 138.6 meq/L). Despite a similar baseline furosemide dose in both groups (median 200 mg), the hyponatraemia group received higher in-hospital furosemide (280 vs. 200 mg, in both groups, respectively, p < 0.001) which represented a higher percentage of furosemide utilisation relative to baseline, compared with the normonatraemia group (33% vs 0%, in both groups respectively, p = 0.007). With in-hospital diuresis, the Na level of hyponatraemic subjects started significantly increasing at discharge and up to 6 months after randomisation-all relative to baseline. Hyponatraemic patients had significantly lower systolic blood pressure (SBP) longitudinally at multiple time points compared with normonataremic patients, but it did not further decrease despite the higher furosemide dose in the former group. CONCLUSION Patients with ADHF and hyponatraemia on admission had a higher degree of congestion and required higher doses of furosemide, compared with normonatraemic subjects. The lower Na and SBP in this instance should not lead to withholding or minimising diuretic dosage which should rather be dictated by volume status.