Everything we always wanted to know about furosemide but were afraid to ask

Huang, Xiaohua; Mees, E. J. Dorhout; Vos, Pieter C.; Hamza, Shereen M.; Braam, Branko

doi:10.1152/ajprenal.00476.2015

Cited by 92 publications

(89 citation statements)

References 160 publications

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“…107 Loop diuretics may not affect TGF, because inhibition of the Na-K-2Cl-cotransporter also blocks solute transport into macula densa cells, 107 although discussion is ongoing. 111 Thiazide diuretics and epithelial sodium channel blockers act distally of the macula densa and do not influence TGF signals. However, (novel selective nonsteroidal) mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone, finerenone)…”

Section: Diureticsmentioning

confidence: 99%

Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment

Tonneijck

Muskiet

Smits

et al. 2017

JASN

615

490

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An absolute, supraphysiologic elevation in GFR is observed early in the natural history in 10%-67% and 6%-73% of patients with type 1 and type 2 diabetes, respectively. Moreover, at the single-nephron level, diabetes-related renal hemodynamic alterations-as an adaptation to reduction in functional nephron mass and/or in response to prevailing metabolic and (neuro)hormonal stimuli-increase glomerular hydraulic pressure and transcapillary convective flux of ultrafiltrate and macromolecules. This phenomenon, known as glomerular hyperfiltration, classically has been hypothesized to predispose to irreversible nephron damage, thereby contributing to initiation and progression of kidney disease in diabetes. However, dedicated studies with appropriate diagnostic measures and clinically relevant end points are warranted to confirm this assumption. In this review, we summarize the hitherto proposed mechanisms involved in diabetic hyperfiltration, focusing on ultrastructural, vascular, and tubular factors. Furthermore, we review available evidence on the clinical significance of hyperfiltration in diabetes and discuss currently available and emerging interventions that may attenuate this renal hemodynamic abnormality. The revived interest in glomerular hyperfiltration as a prognostic and pathophysiologic factor in diabetes may lead to improved and timely detection of (progressive) kidney disease, and could provide new therapeutic opportunities in alleviating the renal burden in this population.

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Section: Diureticsmentioning

confidence: 99%

Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment

Tonneijck

Muskiet

Smits

et al. 2017

JASN

615

490

View full text Add to dashboard Cite

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“…Furosemide is excreted from the blood into the urine through the proximal tubules by the human organic anion transporter and inhibits luminal sodium transporters in the loop of Henle from the urinal lumen [ 20 ]. If furosemide administration increases the urine output, it could be assumed that the tubules are functional.…”

Section: Introductionmentioning

confidence: 99%

Response to different furosemide doses predicts AKI progression in ICU patients with elevated plasma NGAL levels

Matsuura

Komaru

Miyamoto

et al. 2018

Ann. Intensive Care

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BackgroundFurosemide responsiveness (FR) is determined by urine output after furosemide administration and has recently been evaluated as a furosemide stress test (FST) for predicting severe acute kidney injury (AKI) progression. Although a standardized furosemide dose is required for FST, variable dosing is typically employed based on illness severity, including renal dysfunction in the clinical setting. This study aimed to evaluate whether FR with different furosemide doses can predict AKI progression. We further evaluated the combination of an AKI biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), and FR for predicting AKI progression.ResultsWe retrospectively analyzed 95 patients who were treated with bolus furosemide in our medical–surgical intensive care unit. Patients who had already developed AKI stage 3 were excluded. A total of 18 patients developed AKI stage 3 within 1 week. Receiver operating curve analysis revealed that the area under the curve (AUC) values of FR and plasma NGAL were 0.87 (0.73–0.94) and 0.80 (0.67–0.88) for AKI progression, respectively. When plasma NGAL level was < 142 ng/mL, only one patient developed stage 3 AKI, indicating that plasma NGAL measurements were sufficient to predict AKI progression. We further evaluated the performance of FR in 51 patients with plasma NGAL levels > 142 ng/mL. FR was associated with AUC of 0.84 (0.67–0.94) for AKI progression in this population with high NGAL levels.ConclusionsAlthough different variable doses of furosemide were administered, FR revealed favorable efficacy for predicting AKI progression even in patients with high plasma NGAL levels. This suggests that a combination of FR and biomarkers can stratify the risk of AKI progression in a clinical setting.Electronic supplementary materialThe online version of this article (10.1186/s13613-018-0355-0) contains supplementary material, which is available to authorized users.

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“…Furosemide is a potent and widely used diuretic drug that inhibits the Na + ‐K + ‐Cl − cotransporter in the ascending limb of the loop of Henle . Furosemide influences the clearance of many exogenous and endogenous compounds, including carnitine .…”

Section: Discussionmentioning

confidence: 99%

Carnitine and γ‐Butyrobetaine Stimulate Elimination of Meldonium due to Competition for OCTN2‐mediated Transport

Liepinsh

Makarova

Sevostjanovs

et al. 2017

Basic Clin Pharma Tox

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Meldonium (3-(2,2,2-trimethylhydrazinium)propionate) is the most potent clinically used inhibitor of organic cation transporter 2 (OCTN2). Inhibition of OCTN2 leads to a decrease in carnitine and acylcarnitine contents in tissues and energy metabolism optimization-related cardioprotective effects. The recent inclusion of meldonium in the World Anti-Doping Agency List of Prohibited Substances and Methods has raised questions about the pharmacokinetics of meldonium and its unusually long elimination time. Therefore, in this study, the rate of meldonium washout after the end of the treatment was tested with and without administration of carnitine, γ-butyrobetaine (GBB) and furosemide to evaluate the importance of competition for OCTN2 transport in mice. Here, we show that carnitine and GBB administration during the washout period effectively stimulated the elimination of meldonium. GBB induced a more pronounced effect on meldonium elimination than carnitine due to the higher affinity of GBB for OCTN2. The diuretic effect of furosemide did not significantly affect the elimination of meldonium, carnitine and GBB. In conclusion, the competition of meldonium, carnitine and GBB for OCTN2-mediated transport determines the pharmacokinetic properties of meldonium. Thus, due to their affinity for OCTN2, GBB and carnitine but not furosemide stimulated meldonium elimination. During long-term treatment, OCTN2-mediated transport ensures a high muscle content of meldonium, while tissue clearance depends on relatively slow diffusion, thus resulting in the unusually long complete elimination period of meldonium.

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Everything we always wanted to know about furosemide but were afraid to ask

Cited by 92 publications

References 160 publications

Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment

Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment

Response to different furosemide doses predicts AKI progression in ICU patients with elevated plasma NGAL levels

Carnitine and γ‐Butyrobetaine Stimulate Elimination of Meldonium due to Competition for OCTN2‐mediated Transport

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