Renal tubular secretion and effects of furosemide

Odlind, Bo; Beermann, B

doi:10.1038/clpt.1980.111

Cited by 125 publications

(62 citation statements)

References 9 publications

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“…In the majority of studies, GFR increased (5,13,14,71,120,121,133,169) or remained stable (31,42,102,147); in five studies GFR decreased (51,91,100,158). RBF increased in five (71,102,115,121,169), remained stable in three (42,51,120), decreased in one (51), and was not reported in the other studies (5, 13, 14, 31, 91, 100, 133, 147, 158). This clearly illustrates how complex the actions of furosemide on renal hemodynamics are.…”

Section: Questions Regarding Hemodynamics and Vascular Regulation Andmentioning

confidence: 74%

“…Furosemide has been associated with worsening of kidney function in patients treated for volume overload admitted for acute heart failure (104) and even glomerular filtration rate (GFR) responses to furosemide in healthy subjects are variable (5,13,14,31,42,51,71,91,100,102,115,120,121,133,147,158,169). The very strong and short actions of furosemide have been associated with rebound sodium retention, and it has been brought to question whether furosemide would allow the reaching of a new steady state.…”

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confidence: 99%

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

Huang

Mees

Vos

et al. 2016

American Journal of Physiology-Renal Physiology

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Huang X, Dorhout Mees E, Vos P, Hamza S, Braam B. Everything we always wanted to know about furosemide but were afraid to ask. Am J Physiol Renal Physiol 310: F958 -F971, 2016. First published February 24, 2016 doi:10.1152/ajprenal.00476.2015.-Furosemide is a widely used, potent natriuretic drug, which inhibits the Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC)-2 in the ascending limb of the loop of Henle applied to reduce extracellular fluid volume expansion in heart and kidney disease. Undesirable consequences of furosemide, such as worsening of kidney function and unpredictable effects on sodium balance, led to this critical evaluation of how inhibition of NKCC affects renal and cardiovascular physiology. This evaluation reveals important knowledge gaps, involving furosemide as a drug, the function of NKCC2 (and NKCC1), and renal and systemic indirect effects of NKCC inhibition. Regarding renal effects, renal blood flow and glomerular filtration rate could become compromised by activation of tubuloglomerular feedback or by renin release, particularly if renal function is already compromised. Modulation of the intrarenal renin angiotensin system, however, is ill-defined. Regarding systemic effects, vasodilation followed by nonspecific NKCC inhibition and changes in venous compliance are not well understood. Repetitive administration of furosemide induces short-term (braking phenomenon, acute diuretic resistance) and long-term (chronic diuretic resistance) adaptations, of which the mechanisms are not well known. Modulation of NKCC2 expression and activity in kidney and heart failure is ill-defined. Lastly, furosemide's effects on cutaneous sodium stores and on uric acid levels could be beneficial or detrimental. Concluding, a considerable knowledge gap is identified regarding a potent drug with a relatively specific renal target, NKCC2, and renal and systemic actions. Resolving these questions would increase the understanding of NKCCs and their actions and improve rational use of furosemide in pathophysiology of fluid volume expansion. extracellular fluid volume; natriuresis; renal function; chronic kidney disease; heart failure DIURETICS BLOCKING THE Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC) have an important place in the treatment of fluid overload, specifically in the context of kidney disease and heart failure (64). Of the drugs that inhibit the NKCC2 in the loop of Henle (furosemide, bumetanide, torsemide, ethacrynic acid), furosemide is most commonly applied (66) and Ͼ40 million prescriptions are dispensed every year in the USA (66a). However, many uncertainties remain about intrarenal and systemic actions of furosemide, including its two main targets NKCC1 and NKCC2.Clinically, there are a number of undesirable consequences of the use of furosemide, of which the pathophysiological mechanisms have not been sufficiently investigated. Furosemide has been associated with worsening of kidney function in patients treated for volume overload admitted for acute heart failure (104) and even glomerular filtration rate (GFR) ...

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Section: Questions Regarding Hemodynamics and Vascular Regulation Andmentioning

confidence: 74%

mentioning

confidence: 99%

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

Huang

Mees

Vos

et al. 2016

American Journal of Physiology-Renal Physiology

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“…Significant correlations were observed between the urinary furosemide and its diure tic effects which is explained by the well-known concept that the diuretic effects of furosemide depend on its urinary amount (11). In addition, the regression lines between urinary furosemide and its diuretic effects after amikacin treatment did not significantly differ from those before treatment.…”

Section: Resultsmentioning

confidence: 53%

Chronopharmacology of Furosemide in Rats with Amikacin-Induced Acute Renal Damage.

et al. 1992

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ABSTRACT-To examine the influence of amikacin-induced acute renal damage on the urinary excre tion of furosemide and the time-dependent variation in the urinary amount of the agent, amikacin (1.2 g/kg) was given intraperitoneally to Wistar rats. Study I: Three percent b.w. of 1% NaCI solution was given orally before and after amikacin treatment, and an 8-hour urine for N-acetyl-,Q-o-glucosaminidase (NAG) was collected. Study II: Furosemide (30 mg/kg) in 3% b.w. of 1% NaCI solution was given orally at 12 a.m. or 12 p.m. before and after amikacin treatment, and an 8-hour urine for sodium and furosemide was collected. Following amikacin treatment, urinary excretion of NAG increased, while urine volume and urinary excretion of sodium and furosemide decreased. Urinary excretion of furosemide and its diuretic effects were significantly greater at 12 a.m. than at 12 p.m. before and after treatment. However the time-dependent differences in these parameters were diminished by amikacin treatment. These results suggest that the urinary excretion of furosemide is reduced and the extents of the time-dependent variation in the urinary furosemide and its diuretic effects are altered in rats with amikacin-induced renal damage.

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“…Effects on fractional sodium excretion (ENa%) ( Figure 5 piretanide are dependent on active secretion by renal tubular cells and therefore on its tubular fluid concentration (Odlind, 1979). Urinary excretion of sodium closely paralleled the excretion of bumetamide in patients with severe renal failure (Berg et al, 1976).…”

Section: Stuiy Bmentioning

confidence: 99%

The pharmacokinetics and diuretic effects of piretanide in chronic renal insufficiency.

Berg¹,

Walstad²,

Bergh³

1983

Brit J Clinical Pharma

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The pharmacokinetics of piretanide, a new loop diuretic, were studied in four patients with GFR 4.7‐14.8 ml/min. An oral dose of piretanide 18 mg was given at 08.00 h in two patients and at 08.00 h and 14.00 h in two. Blood samples were drawn after 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. Serum concentrations of piretanide were estimated by radioimmunoassay. The peak serum concentration of piretanide (1‐2 h after drug administration) was 510‐880 ng/ml, independent of renal function. Elimination half life (t1/2) was 1.2‐4.1 h, area under the curves (AUC(0,24)) 1.63‐2.44 micrograms ml‐1 h, volume of distribution (Vz) 0.30–0.741#kg, total plasma clearance (CL) 122.8‐184.0 ml/min and renal clearance (CLR) 1.5‐5.2 ml/min. The clinical effects of oral treatment with piretanide 18 mg twice daily were compared with bumetanide 3 mg twice daily in eight patients with renal failure (GFR 2.2‐24.5 ml/min). Both drugs equally increased the 24 h output of urine (delta V), sodium (delta UNaV), chloride (delta UC1V), potassium (delta UKV) and calcium (delta UCaV). Fractional excretion of sodium (ENa%) was doubled by piretanide in patients with GFR less than 8 ml/min while a five fold increase was found in patients with GFR greater than 8 ml/min. The onset of effect was the same for both drugs, but the duration exceeded 6 h only for piretanide. Both drugs were most effective on the first of two consecutive treatment days. Delta UC1V was always greater than delta UNaV and urinary phosphate excretion was unchanged, as expected of a loop diuretic without significant proximal effects. Metabolic or clinical side effects were not noticed.

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Renal tubular secretion and effects of furosemide

Cited by 125 publications

References 9 publications

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

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

Chronopharmacology of Furosemide in Rats with Amikacin-Induced Acute Renal Damage.

The pharmacokinetics and diuretic effects of piretanide in chronic renal insufficiency.

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