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Randomized Phase II Study Comparing Mannitol with Furosemide for the Prevention of Renal Toxicity Induced by Cisplatin-based Chemotherapy with Short-term Low-volume Hydration in Advanced Non-small Cell Lung Cancer: The OLCSG1406 Study Protocol.
Makimoto, G, Ichihara, E, Hotta, K, Ninomiya, K, Oze, I, Minami, D, Ninomiya, T, Kubo, T, Ohashi, K, Tabata, M, et al
Acta medica Okayama. 2018;(3):319-323
Abstract
Although cisplatin-based chemotherapy shows a survival advantage compared to carboplatin for treating advanced non-small cell lung cancer, high-volume hydration and a long infusion time are necessary to avoid nephrotoxicity, and cisplatin-based chemotherapy has been difficult to administer in outpatient settings. A low-volume hydration method using mannitol or furosemide as forced diuresis was recently introduced, but there are no clear conclusions regarding which agent should be used. We describe our ongoing randomized phase II trial (the OLCSG1406 Study) evaluating the efficacy of forced diuresis. This study will clarify whether mannitol or furosemide is more suitable in cisplatin-based chemotherapy with low-volume hydration.
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Diuretic response in patients with acute decompensated heart failure: characteristics and clinical outcome--an analysis from RELAX-AHF.
Voors, AA, Davison, BA, Teerlink, JR, Felker, GM, Cotter, G, Filippatos, G, Greenberg, BH, Pang, PS, Levin, B, Hua, TA, et al
European journal of heart failure. 2014;(11):1230-40
Abstract
AIMS: We studied the characteristics and clinical outcome related to diuretic response and the effects of serelaxin in patients hospitalized for acute heart failure (AHF). METHODS AND RESULTS RELAX-AHF was a double-blind, placebo-controlled trial, enrolling 1161 patients admitted to hospital for AHF who were randomized to 48 h i.v infusions of placebo or serelaxin (30 µg/kg per day) within 16 h from presentation. Diuretic response was defined as Δ weight kg/[(total i.v. dose)/40 mg] + [(total oral dose)/80 mg)] furosemide (or equivalent loop diuretic dose) up to day 5. Median diuretic response was -0.42 (-1.00, -0.14) kg/40 mg. A poor diuretic response was independently associated with Western-like region (Western Europe, North America, Israel, and Poland), lower diastolic blood pressure, the absence of oedema, higher blood urea nitrogen, and lower levels of aspartate aminotransferase and potassium (all P < 0.01). Randomization to serelaxin was associated with lower doses of i.v. loop diuretics and slightly less weight loss, resulting in a neutral effect on diuretic response. Worse diuretic response was independently associated both with less relief of dyspnoea, measured with a visual analogue scale (VAS) at day 5 (primary endpoint; P = 0.0002), and with a higher risk of cardiovascular death or rehospitalization for heart failure or renal failure through day 60 (secondary endpoint, P < 0.0001), but not with increased 180-day cardiovascular mortality (P = 0.507). CONCLUSIONS In patients hospitalized for AHF, a poor diuretic response was associated with a poor in-hospital and early post-discharge clinical outcome. Serelaxin had a neutral effect on diuretic response. TRIAL REGISTRATION NCT00520806.
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Clinical features and outcome in hospitalized heart failure in Japan (from the ATTEND Registry).
Sato, N, Kajimoto, K, Keida, T, Mizuno, M, Minami, Y, Yumino, D, Asai, K, Murai, K, Muanakata, R, Aokage, T, et al
Circulation journal : official journal of the Japanese Circulation Society. 2013;(4):944-51
Abstract
BACKGROUND Hospitalized heart failure (HHF) is a critical issue in Japan. To improve its management and outcomes, the clinical features, in-hospital management, and outcomes should be analyzed to improve the guidelines for HHF. METHODS AND RESULTS The acute decompensated heart failure syndromes (ATTEND) registry is the largest study of HHF in Japan. The present report covers the clinical features and in-hospital management of HHF patients. The data from 4,842 enrolled patients have demonstrated that most Japanese HHF patients are elderly, with new onset, and a history of hypertension and orthopnea on admission. During hospitalization, furosemide and carperitide were commonly used and the length of stay was extremely long (mean 30 days), with 6.4% in-hospital mortality. CONCLUSIONS The findings of the present study suggest the following: (1) the focus for hypertensive elderly and diabetic patients should be on primary prevention of HHF,(2) more intensive management with noninvasive positive pressure ventilation should be performed at the urgent stage, (3) it is necessary to clarify the clinical benefit of carperitide and angiotensin-receptor blockers, because they are commonly used in Japan, and (4) it is necessary to clarify the relationship between in-hospital mortality and length of stay from the viewpoint of both outcome and cost of patient care.
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Assessing parenteral diuretic treatment of decompensated heart failure in the community.
Austin, J, Hockey, D, Williams, WR, Hutchison, S
British journal of community nursing. 2013;(11):528, 530-4
Abstract
Referrals of 46 patients with decompensated end-stage heart failure were reviewed by a community heart-failure specialist nurse as part of a pilot study to determine patient numbers suitable for parenteral diuretic treatment at home, and the appropriateness of the Mini Nutritional Assessment (MNA), Edmonton Symptom Assessment System (ESAS) and Carer's Stress Scales. Triage of patients resulted in the following care pathways: 14 (30%) received intravenous therapy, 11 (24%) received subcutaneous therapy, 9 (20%) required adjustment of medication, 8 (17%) could not be treated because of limited staffing resource, 4 (9%) met study exemption criteria. There were no adverse events following furosemide infusion. The majority of intravenous and subcutaneous treatments took 1-7 days (total 187 days). Parenteral diuretic therapy prevented admissions and reduced the severity heart failure symptoms in particular oedema. Patients and carers appreciated the service, which had a positive effect on carers stress. Of the nursing tools, the ESAS and the Carer's Stress Scales proved useful in the management of patients.
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Pathophysiology of renal calcium handling in acromegaly: what lies behind hypercalciuria?
Kamenický, P, Blanchard, A, Gauci, C, Salenave, S, Letierce, A, Lombès, M, Brailly-Tabard, S, Azizi, M, Prié, D, Souberbielle, JC, et al
The Journal of clinical endocrinology and metabolism. 2012;(6):2124-33
Abstract
BACKGROUND Hypercalciuria is frequent in patients with acromegaly, but it is unclear how GH/IGF-I regulate renal calcium handling. Elevated fasting plasma calcium levels despite increased glomerular filtration suggest enhanced renal calcium reabsorption. OBJECTIVE The aim of this study was to investigate the impact of acromegaly on phosphocalcium metabolism. DESIGN AND SETTING We conducted a prospective sequential study at a tertiary referral medical center and clinical investigation center (www.ClinicalTrials.gov Identifier: NCT00531908). INTERVENTION Sixteen consecutive patients (five females/11 males) with acromegaly received a single iv infusion of 25 mg of furosemide to induce an acute increase in calcium and magnesium delivery to distal tubular segments during a high-sodium diet with stable dietary calcium, magnesium, and phosphate intake. MEASUREMENTS Baseline plasma and urine electrolytes, plasma calciotropic hormones, and furosemide-induced changes in the fractional excretion and tubular reabsorption of Na, Ca, and Mg were measured before and 6 months (range, 1-12) after effective treatment of acromegaly. RESULTS Serum IGF-I concentrations normalized in all the patients after acromegaly treatment. Compared with controlled acromegaly, active acromegaly was associated with higher fasting plasma (P = 0.0002) and urinary calcium (P = 0.0003) levels, lower PTH levels (P = 0.0075), higher calcitriol levels (P = 0.0137), higher phosphatemia (P<0.0001) and tubular phosphate reabsorption (P = 0.0002), and a lower calciuric (P = 0.0327) but not magnesiuric response to furosemide related to higher baseline and postfurosemide tubular calcium (P = 0.0034 and P = 0.0081, respectively), but not magnesium reabsorption. CONCLUSION The IGF-I-mediated and PTH-independent increase in calcitriol synthesis in acromegaly is responsible for both absorptive hypercalciuria and increased fasting plasma calcium linked to enhanced distal tubular calcium reabsorption, as shown by the selectively diminished calciuric response to furosemide.
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Validation of a therapeutic scheme for the treatment of resistant hypertension.
Segura, J, Cerezo, C, Garcia-Donaire, JA, Schmieder, RE, Praga, M, de la Sierra, A, Ruilope, LM
Journal of the American Society of Hypertension : JASH. 2011;(6):498-504
Abstract
We tested the hypothesis that a therapeutic strategy of substituting the diuretic (most commonly hydrochlorothiazide) with chlorthalidone (50 mg/day), and, if needed, the calcium channel blocker with the highest dose of the most commonly used calcium antagonist (amlodipine 10 mg), and adding on top a direct renin inhibitor (aliskiren 300 mg) is effective to treat resistant hypertensive patients not responding to spironolactone. The scheme was tested in a group of 76 patients who had true treatment resistant hypertension (24-hour mean blood pressure ≥130/80 mm Hg while receiving three or more drugs). An effective response to spironolactone was defined as 24-hour ambulatory systolic blood pressure (SBP) drop by more than 20 mm Hg, and was obtained with 25-50 mg in 60 patients (78.9%). In patients with inadequate response to spironolactone (n = 16), we administered the triple combination plus the remaining therapy, a mean decrease of 29 mm Hg (95% CI 11-48; P = .004) for SBP and 12 mm Hg (95% CI: 4-20 mm Hg) for diastolic BP were observed. In only 1 of 16 patients (6%), the response was considered as insufficient. These data indicate the need for further testing this scheme that looks really promising to treat resistant hypertensive patients not responding to spironolactone.
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Use of small doses of furosemide in chronic kidney disease patients with residual renal function undergoing hemodialysis.
Lemes, HP, Araujo, S, Nascimento, D, Cunha, D, Garcia, C, Queiroz, V, Ferreira-Filho, SR
Clinical and experimental nephrology. 2011;(4):554-9
Abstract
BACKGROUND The objective of the present study was to verify whether chronic renal patients on hemodialysis (HD) with residual diuresis who were using small doses of furosemide present different levels of urinary volume and sodium excretion compared to patients with residual diuresis who do not use this drug. METHODS We studied 19 chronic renal patients on HD who presented any level of residual diuresis. Urine was collected during the 24-h interdialytic period, and physical examinations and blood sampling took place immediately before the start of HD. Patients were divided into two groups: the diuretic group (DG, n = 10), in which patients had been using 40 mg of furosemide for at least 3 months, and the non-diuretic group (NDG, n = 9), in which patients used no diuretics. RESULTS Although both groups presented the same average glomerular filtration rate (p > 0.05) and time in dialysis (p > 0.05) the DG presented an average of twice the urinary volume in 24 h (1142 ± 184 vs. 453 ± 135 ml/24 h, respectively; p = 0.008) and double the total excreted sodium mass compared to patients in the NDG (112 ± 22.4 vs. 45.2 ± 16.0 mEq/24 h, respectively; p = 0.02). CONCLUSION The results of this study have shown that chronic use of small doses of furosemide in chronic renal patients with residual diuresis could increase urinary volume and sodium excretion compared to patients who did not use this drug.
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Increased understanding of intestinal drug permeability determined by the LOC-I-GUT approach using multislice computed tomography.
Knutson, T, Fridblom, P, Ahlström, H, Magnusson, A, Tannergren, C, Lennernäs, H
Molecular pharmaceutics. 2009;(1):2-10
Abstract
This study further evaluated the in vivo single-pass perfusion technique (LOC-I-GUT) in three different ways. First, the intestinal radius of the human small intestinal segment was measured on plain X-ray films; second, evaluation was performed by applying multislice computed tomography investigations; and third, furosemide was used as model drug in a transport study. In total 17 (6 + 4 +7) intubation/perfusion studies were performed in healthy volunteers. Mixobar was used as a positive radiographic contrast agent in the first six volunteers when plain film examination was made, followed by four studies using multislice computed tomography. Mantel area calculations of the perfused segment after X-ray investigations using barium as contrast were determined to be 101.0 +/- 2.9 cm2. Maximal dilatation of the closed segment with room air as contrast and using MSCT revealed a mantel area of 121.30 +/- 7.0 cm2 (P < 0.01). Thus, the mantle area increased a further 20% when the bowel was fully distended, reflecting different physiologic distention patterns for air and fluid. A jejunal single-pass perfusion study was performed in a further seven volunteers. In each experiment furosemide was perfused during 200 min, and in the treatment period (100-200 min), fexofenadine was added to the perfusion solution. The mean (+/-SD) P (eff) for furosemide was 0.17 +/- 0.07 and 0.12 +/- 0.09 x 10-4 cm/s in the control and treatment period, respectively. This study showed that the calculation of human in vivo permeability is based on physiological values, which are important for the wide application of these in vivo permeability data in physiologically based pharmacokinetic modeling.
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Treatment of severe edema in children with nephrotic syndrome with diuretics alone--a prospective study.
Kapur, G, Valentini, RP, Imam, AA, Mattoo, TK
Clinical journal of the American Society of Nephrology : CJASN. 2009;(5):907-13
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Abstract
BACKGROUND AND OBJECTIVE Severe edema in children with nephrotic syndrome (NS) may be associated with volume contraction (VC) or volume expansion (VE). Usually, severe edema in children is treated with intravenous (IV) albumin and diuretics, which is appropriate for VC patients. However, in VE patients, this can precipitate fluid overload. The objective of this study was to evaluate treatment of severe edema in NS with diuretics alone. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Thirty NS patients with severe edema were enrolled in this prospective study in two phases. VC was diagnosed based on fractional excretion of sodium (FeNa) <1%. VC patients received IV albumin and furosemide. VE patients received IV furosemide and oral spironolactone. On the basis of phase 1 observations, FeNa <0.2% identified VC in 20 phase 2 patients. RESULTS All phase 1 patients had FeNa <1%. Phase 1 patients when reanalyzed based on a FeNa cutoff of 0.2%; it was noted that VC patients had higher BUN, BUN/creatinine ratio, urine osmolality, and lower FeNa and urine sodium compared with VE patients. Similar results were observed in phase 2. VC patients had significantly higher renin, aldosterone, and antidiuretic hormone levels. In phase 2, 11 VE patients received diuretics alone and 9 VC patients received albumin and furosemide. There was no difference in hospital stay and weight loss in VC and VE groups after treatment. CONCLUSIONS FeNa is useful in distinguishing VC versus VE in NS children with severe edema. The use of diuretics alone in VE patients is safe and effective.
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Whites excrete a water load more rapidly than blacks.
Weder, AB, Gleiberman, L, Sachdeva, A
Hypertension (Dallas, Tex. : 1979). 2009;(4):715-8
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Abstract
A recent report demonstrated a racial difference in response to furosemide compatible with increased ion reabsorption in the thick ascending limb of the loop of Henle in blacks. Urinary dilution is another function of the loop-diuretic-sensitive Na,K,2Cl cotransporter in the thick ascending limb, and racial differences in urinary diluting capacity have not been reported previously. We assessed diluting segment (cortical thick ascending limb and distal convoluted tubule) function in black and white normotensives in 2 studies using a water-loading approach. In both studies, we found that whites excreted a water load more rapidly than blacks. In the first study, the final free water clearance rates (mean+/-SD) were 7.3+/-4.7 mL/min in whites (n=17, 7 females and 10 males) and 3.8+/-3.6 mL/min in blacks (n=14, 9 females and 5 males; P<0.03). In the second study, final free water clearance rates were 8.3+/-2.6 mL/min in whites (n=17, 8 females and 9 males) and 6.4+/-1.8 mL/min in blacks (n=11, 8 females and 3 males; P<0.01). We found no evidence of a racial difference in renal proximal tubular fluid reabsorption as assessed by renal endogenous lithium clearance or in plasma vasopressin level that could explain the difference in free water excretion. We conclude that our observations are most consistent with a lower capacity of ion reabsorption in the renal diluting segment in blacks. Slower excretion of an acute water load may have been an advantage during natural selection of humans living in arid, hot climates.