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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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OUTpatient intravenous LASix Trial in reducing hospitalization for acute decompensated heart failure (OUTLAST).
Hamo, CE, Abdelmoneim, SS, Han, SY, Chandy, E, Muntean, C, Khan, SA, Sunkesula, P, Meykler, M, Ramachandran, V, Rosenberg, E, et al
PloS one. 2021;(6):e0253014
Abstract
BACKGROUND Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. The current study aimed to investigate the feasibility, safety, and efficacy of outpatient furosemide intravenous (IV) infusion following hospitalization for ADHF. METHODS In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3h, biweekly for a one-month period following ADHF hospitalization. Patients in Groups 2/3 also received a comprehensive HF-care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment and education. Echocardiography, quality of life and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF. RESULTS Overall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American). There were a total of 14 (15%) hospitalizations for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p = 0.11; p = 0.037 comparing Groups 2 and 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores. CONCLUSION The use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.
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Potassium citrate vs. hydrochlorothiazide to reduce urinary calcium excretion in calcium oxalate stone patients with hypercalciuria: a prospective randomized study.
Solak, V, Gökce, Mİ, Yaman, Ö
International urology and nephrology. 2021;(9):1791-1796
Abstract
PURPOSE Calcium oxalate (Ca-Ox) is the most common stone composition and one of the most common 24-h urine anomalies is hypercalciuria. The purpose of this study was to evaluate the efficacy of potassium citrate (K-CIT) for prevention of hypercalciuria in comparison with hydrochlorothiazide (HCT) in patients with calcium oxalate stones and hypercalciuria. MATERIALS AND METHODS In this prospective randomized study, patients were randomized to receive either HCT (50 mg/day) or K-CIT (40 mEq/day) following achieving stone-free status. Treatment was continued for 6 months. 24 h urine analysis was performed prior to treatment and repeated at third month and measured parameters were volume, calcium, oxalate, citrate, sodium, and uric acid. Stone recurrence was evaluated with KUB and ultrasonography at 6th and 12th months. RESULTS Data of 40 patients in each arm were evaluated. Mean 24 h urine calcium levels decreased to 205 ± 54.5 mg/day and 220.6 ± 96.3 mg/day in the K-CIT and HCT groups, respectively, and difference was not significant (p = 0.931). The reduction compared to pretreatment values was statistically significant in both groups. Urinary citrate levels also significantly increased in both groups and level of increase was significantly higher in K-CIT group. At 12th month, ultrasonography revealed stones in two patients in HCT group, and in one patient in the K-CIT group. CONCLUSIONS K-CIT provided significantly reduced calcium and increased citrate excretion in patients Ca-Ox stone patients with hypercalciuria. The efficacy in decreasing calcium excretion was comparable to HCT treatment. K-CIT can be used for medical prophylaxis of Ca-OX stone patients with hypercalciuria.
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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.
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Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.
Jackson, AM, Dewan, P, Anand, IS, Bělohlávek, J, Bengtsson, O, de Boer, RA, Böhm, M, Boulton, DW, Chopra, VK, DeMets, DL, et al
Circulation. 2020;(11):1040-1054
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Abstract
BACKGROUND In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
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Effects of hydrochlorothiazide on drainage volume and seroma formation in deep inferior epigastric perforator flap breast reconstruction: Randomized controlled trial.
Suh, YC, Oh, TM, Lee, YH, Kim, EK, Han, HH, Eom, JS
Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2020;(4):663-672
Abstract
BACKGROUND Seroma is a recognized complication encountered at the reconstructed breast and donor site after abdominal-based breast reconstruction. Seroma is caused by lymphatic channel disruption and the formation of a large space between the deep fascia during flap elevation. Surgical techniques to preserve the lymphatics and secure the closure of the donor site can reduce seroma formation. This study investigated the safety and effectiveness of the diuretic hydrochlorothiazide at reducing interstitial fluid accumulation and seroma formation during deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS Sixty patients with breast cancer who underwent skin- or nipple-sparing mastectomy and DIEP flap reconstruction were enrolled between August 2016 and June 2017. The patients were randomly assigned to receive either 25 mg per day of hydrochlorothiazide from the second to the twentieth day after surgery (treatment) or no diuretic (control). The clinicopathological characteristics, drainage time, and drainage volume were statistically compared between the two groups. RESULTS The average total drainage volume at the donor site was 291 mL in the treatment group and 434 mL in the control group (p = 0.003). The differences in body mass index and flap weight between the two groups were not statistically significant (p = 0.879 and p = 0.963, respectively). No hypotension or electrolyte imbalance was noted during the follow-up. CONCLUSIONS Intake of 25 mg per day of hydrochlorothiazide tablets effectively reduced the total abdominal drainage volume and removal time of indwelling drains. However, the adverse effects should be further investigated in a large population and multiracial cohort before using hydrochlorothiazide for seroma prevention.
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Pharmacokinetic Interaction Among Telmisartan, Amlodipine, and Hydrochlorothiazide After a Single Oral Administration in Healthy Male Subjects.
Moon, SJ, Jeon, JY, Yu, KS, Kim, MG
Clinical therapeutics. 2019;(11):2273-2282
Abstract
PURPOSE Hypertension is a major risk factor for cardiovascular diseases, necessitating hypertension control. Antihypertensive drugs are more potent when administered in combinations of 2 or 3 different classes of drugs. One such therapy includes a combination of an angiotensin receptor blocker, a calcium channel blocker, and a diuretic. The objective of this study was to evaluate the pharmacokinetic interaction among telmisartan, amlodipine, and hydrochlorothiazide. METHODS A randomized, open-label, 3-period, 6-sequence, 3-treatment, single-dose crossover study was conducted in healthy male subjects. Subjects were randomly assigned to 1 of 6 sequences and one of the following treatments was administered in each period: treatment A, co-administration of one tablet of telmisartan 80 mg and one tablet of amlodipine 10 mg; treatment B, one tablet of hydrochlorothiazide 25 mg alone; and treatment C, co-administration of all 3 investigational products. Serial blood samples were collected up to 144 hours postdose. Plasma drug concentrations were measured by using LC/MS-MS. Pharmacokinetic parameters, including Cmax and AUC0-last, were determined by using noncompartmental analysis. The geometric least squares mean ratios and associated 90% CIs of log-transformed Cmax and AUC0-last for separate administration or co-administration were calculated to evaluate pharmacokinetic interactions. FINDINGS Twenty-seven subjects completed the study. The geometric least squares mean ratios and 90% CIs of Cmax and AUC0-last were 1.02 (0.85-1.21) and 1.04 (0.97-1.13) for telmisartan; 1.00 (0.95-1.04) and 0.95 (0.91-0.99) for amlodipine; and 0.88 (0.82-0.96) and 0.86 (0.82-0.90) for hydrochlorothiazide, respectively. No serious adverse events were recorded, and all reported adverse events were of mild intensity. IMPLICATIONS The pharmacokinetic parameters of telmisartan, amlodipine, and hydrochlorothiazide when administered separately or co-administered were compared, and all the parameters met the criteria for pharmacokinetic equivalence. Combination therapy of these 3 drugs had no significant impact on the pharmacokinetic parameters of each drug. (ClinicalTrials.gov Identifier: NCT03889145).
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Heart Failure Prevention in Older Patients Using Intensive Blood Pressure Reduction: Potential Role of Diuretics.
Upadhya, B, Lovato, LC, Rocco, M, Lewis, CE, Oparil, S, Cushman, WC, Kostis, JB, Rodriguez, CJ, Cho, ME, Cloud, LW, et al
JACC. Heart failure. 2019;(12):1032-1041
Abstract
OBJECTIVES This study assessed the potential role of differential diuretic drugs in preventing incident acute decompensated heart failure (ADHF) in the SPRINT (Systolic Blood Pressure Intervention Trial) study. BACKGROUND SPRINT showed that intensive blood pressure reduction in older patients (50 to 97 years of age) resulted in 36% fewer incident cases of ADHF. However, some investigators have questioned whether this was due merely to intergroup differences in diuretic medications. METHODS Detailed use of medication data prospectively collected throughout the trial were examined. RESULTS ADHF events occurred in 173 of 9,361 participants. Diuretic medication increased in both arms from screening to baseline visit (from 45% to 50% in the standard arm; and from 43% to 63% in the intensive arm) and then remained steady. The lowest use of diuretic agents was among participants in the standard arm who never had an ADHF event. Withdrawal of diuretic agents at the baseline visit occurred in 6.1% (n = 284) of participants in the standard arm and 2.3% (n = 107) of participants in the intensive arm. Of these, only 11 developed ADHF during the trial (10 in the standard arm, 1 in the intensive arm), and only 1 occurred ≤1 month after diuretic withdrawal. The benefit of ADHF reduction remained significant even after excluding those 11 participants (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.5 to 0.94; p = 0.02). Most ADHF events occurred in participants who were taking prescribed diuretic therapy at the last visit, prior to the ADHF event. There was limited use of loop (<6%) and potassium-sparing diuretic agents (2%). Diuretic use was not a predictor of ADHF (HR: 0.96; 95% CI: 0.66 to 1.40; p = 0.83). CONCLUSIONS No evidence was found to suggest that the reduction in new ADHF events in SPRINT was due to differential diuretic use. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).
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Prevention of Contrast-induced Nephropathy in Patients with Chronic Kidney Disease Undergoing Elective Coronary Angioplasty or Angiography with Sodium Potassium Citrate Solution, a Double Blind Randomized Clinical Trial.
Ghorbani, A, Yazdankhah, S, Adel, MH, Tabesh, H, Sattari, AR, Sattari, SA, Heybar, H, Madjidi, S
Iranian journal of kidney diseases. 2019;(3):182-190
Abstract
INTRODUCTION Contrast-induced nephropathy (CIN) is a frequent complication of contrast exposure. A recent study suggested that Na/K citrate might have a preventive role. We investigated the efficacy of Na/K citrate to prevent CIN in patients with renal dysfunction undergoing coronary intervention. METHODS The randomized, double-blind, placebo-controlled trial included 201 patients with estimated creatinine clearance < 90 mL/ min, randomized to receive oral Na/K citrate plus saline infusion (treatment group, 104 patients) or oral water plus saline infusion (placebo group, 97 patients). CIN was defined as an absolute increase of serum creatinine ≥ 0.5 mg/dL or a relative increase ≥ 25% or a relative decrease of estimated GFR ≥ 25% within 5 days. RESULTS CIN occurred in 22 patients (12.29%); 10 (11%) in treatment group and 12 (13.6%) in placebo group (P > .05). Post-exposure Cr values were not significantly different between the two groups (1.18 ± 0.28 mg/dL in the placebo vs. 1.15 ± 0.29 mg/dL in the treatment group, P > .05). CIN-negative patients in the treatment group showed a significantly higher increase in urine pH than that of CIN-positive patients (1.642 ± 0.577 vs. 1.20 ± 0.422, P < .05). CONCLUSION Na/K citrate solution is not effective for prophylaxis of CIN in patients with renal dysfunction. However, a probable preventive effect might exist in a subgroup of patients with at least 1.6 units increase in urine pH values following Na/K citrate administration.
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Diuretic or sodium-restricted diet for obstructive sleep apnea-a randomized trial.
Fiori, CZ, Martinez, D, Montanari, CC, Lopez, P, Camargo, R, Sezerá, L, Gonçalves, SC, Fuchs, FD
Sleep. 2018;(4)
Abstract
STUDY OBJECTIVES Interventions that decrease leg fluid retention reduce obstructive sleep apnea (OSA) severity in nonrandomized experiments. We aimed to investigate in a randomized trial the effect of interventions that reduce fluid volume on OSA severity. METHODS Men diagnosed with severe OSA were randomized to receive daily spironolactone 100 mg + furosemide 20 mg or nutritional counseling to sodium-restricted diet plus placebo pill or placebo pill. All participants underwent home sleep apnea testing at baseline and after 1 week follow-up. The change in apnea-hypopnea index (AHI) was the primary outcome. RESULTS The study included 54 participants and all were assessed at follow-up. The average baseline value of the AHI was similar among groups and from baseline to follow-up the AHI reduced 14.4 per cent (δ value -7.3 events per hour; 95% confidence interval, -13.8 to -0.9) in the diuretic group, 22.3 per cent (-10.7; 95% CI, -15.6 to -5.7) in the diet group, and 0.8 per cent (0.4; 95% CI, -2.5 to 3.2) in the placebo group (p = .001 for time × group interaction). None of the patients had their AHI returned to normal. The reduction in the total body water was 2.2 ± 2.2 L in the diuretic group (p < .001) and 1.0 ± 1.6 l in the low salt diet group (p = .002). Sleepiness and neck circumference were significantly reduced only in the diet group (p = .007 and p < .001 for the time × group interactions, respectively). CONCLUSIONS Interventions to reduce bodily fluid content in men with severe OSA promoted a limited decrease of apnea frequency. This finding suggests that rostral fluid displacement affects only partially the OSA severity and/or that other factors prevail in determining pharyngeal collapsibility. CLINICAL TRIAL Sodium-Restricted Diet and Diuretic in the Treatment of Severe Sleep Apnea (DESALT), https://clinicaltrials.gov/ct2/show/NCT01945801 ClinicalTrials.gov number: NCT01945801.