Urinary excretion of aquaporin‐2 after furosemide and felodipine in healthy humans

Starklint, Jørn; Bech, Jesper Nørgaard; Pedersen, E. B.

doi:10.1080/00365510510013659

Cited by 12 publications

(20 citation statements)

References 19 publications

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“…In the present study, cardiac function was improved in CHF rats treated with Sclederma of Poria cocos (hoelen), with a slight reduction of plasma AVP and renal V2R-AQP2. In contrast, there is no change in plasma BNP levels with the enhancement of AVP-V2R-AQP2 in CHF rats treated with furosemide, which is consistent with previous studies (Starklint et al, 2005(Starklint et al, , 2006. This suggests that Sclederma of Poria cocos (hoelen) may exert its diuretic effect and improve cardiac function by reducing AVP-V2R-AQP2 expression.…”

Section: Discussionsupporting

confidence: 92%

Sclederma of Poria cocos exerts its diuretic effect via suppression of renal aquaporin-2 expression in rats with chronic heart failure

Ren

Lai

et al. 2014

Journal of Ethnopharmacology

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Section: Discussionsupporting

confidence: 92%

Sclederma of Poria cocos exerts its diuretic effect via suppression of renal aquaporin-2 expression in rats with chronic heart failure

Ren

Lai

et al. 2014

Journal of Ethnopharmacology

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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).…”

Section: Questions Regarding Hemodynamics and Vascular Regulation Andmentioning

confidence: 77%

“…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.…”

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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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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“…Second, all patients in this study were free of treatment (specifically diuretic drugs) known to alter the abundance of aquaporin protein in the kidneys and therefore in urine. [25][26][27] Indeed, increased excretion of urinary aquaporin-2 has been demonstrated during furosemide treatment. 27 In the Pedersen study, 9 of 14 patients with cirrhosis received diuretics up to 24 hours prior to urine collection, and in the Ivarsen study all patients were receiving diuretic treatment at the time of urine collection.…”

Section: Discussionmentioning

confidence: 99%

“…[25][26][27] Indeed, increased excretion of urinary aquaporin-2 has been demonstrated during furosemide treatment. 27 In the Pedersen study, 9 of 14 patients with cirrhosis received diuretics up to 24 hours prior to urine collection, and in the Ivarsen study all patients were receiving diuretic treatment at the time of urine collection. Finally, although the technique used to detect urine aquaporin-2 differed among the 3 studies-dot-blot analysis in the Ivarsen study, radioimmunoassay in the Pedersen study, and immunoblot in our study-we do not think this can explain the differences found in aquaporin-2 urinary excretion.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis: Relationship with ascites and hepatorenal syndrome

et al. 2006

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Several experimental models of cirrhosis have shown dysregulation of renal aquaporins in different phases of liver disease. We investigated the urinary excretion of both aquaporin-1 and aquaporin-2 in patients with cirrhosis at different stages of the disease. Twenty-fourhour urine was collected from 11 healthy volunteers, 13 patients with compensated cirrhosis (without ascites), and 20 patients with decompensated cirrhosis (11 with ascites without renal failure and 9 with hepatorenal syndrome). Aquaporin-1 and aquaporin-2 excretion was analyzed by immunoblotting. Urinary aquaporin-2 excretion was reduced in patients with cirrhosis compared to healthy subjects. A progressive decrease in urinary aquaporin-2 excretion was observed as the severity of cirrhosis increased, from compensated cirrhosis to cirrhosis with ascites and hepatorenal syndrome. Patients with hyponatremia had lower urinary aquaporin-2 excretion than patients without hyponatremia. Vasopressin plasma level did not correlate with aquaporin-2 excretion. There were no differences between healthy subjects and patients with cirrhosis with or without ascites in urinary excretion of aquaporin-1, but urinary aquaporin-1 excretion of those with hepatorenal syndrome was extremely low. In conclusion, patients with cirrhosis appear to exhibit a decreased abundance of renal aquaporin-2 and therefore lower water permeability in the collecting tubules. This may represent an adaptive renal response to sodium retention, with expansion of extracellular fluid volume and dilutional hyponatremia observed in those who have cirrhosis with ascites. Finally, aquaporin-1 does not appear to play a role in the progressive dysregulation of extracellular fluid volume in cirrhosis. (HEPATOLOGY 2006;44:1555-1563

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Urinary excretion of aquaporin‐2 after furosemide and felodipine in healthy humans

Abstract: Furosemide treatment increased U-AQP2, AVP, and the activity of the renin-angiotensin-aldosterone system. These changes are most likely compensatory phenomena, which prevent an excess loss of sodium and water. Felodipine tended to increase U-AQP2.

Cited by 12 publications

References 19 publications

Sclederma of Poria cocos exerts its diuretic effect via suppression of renal aquaporin-2 expression in rats with chronic heart failure

Sclederma of Poria cocos exerts its diuretic effect via suppression of renal aquaporin-2 expression in rats with chronic heart failure

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

Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis: Relationship with ascites and hepatorenal syndrome

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