Association between plasma concentration of tolvaptan and urine volume in acute decompensated heart failure patients with fluid overload

Kato, Masashi; Tohyama, Kazuto; Ohya, Toshiyuki; Hiro, Takafumi; Hirayama, Atsushi

doi:10.5603/cj.a2016.0055

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…The suppression of K + currents by TLV in renal epithelial cells could virtually exert an alternative impact on the harness of vasopressin-induced water movement. Synergistic antagonism of vasopressin V 2 receptor and inhibition of these K + currents caused by TLV at the concentrations noted to be achievable in humans (Shoaf et al, 2007; Kato et al, 2016; Oguri et al, 2018a), may also potentially account for its actions on renal epithelial cells. Therefore, determining to what extent such inhibitory actions by TLV or other structurally similar compounds (Tabata et al, 2017) contribute to their therapeutic effectiveness in renal water excretion is worthy of being imperatively investigated, as they have been rampantly used in different types of electrolyte disorders such as hyponatremia (Izumi et al, 2014; Aylwin et al, 2015; Verbalis et al, 2016; Clark et al, 2017; Der-Nigoghossian et al, 2017; Dunlap et al, 2017; Felker et al, 2017; Konstam et al, 2017; Wu et al, 2017a; Berardi et al, 2018; Kogure et al, 2018; Matsukawa et al, 2018; Morris et al, 2018; Sigal et al, 2018; Vidic et al, 2019).…”

Section: Discussionmentioning

confidence: 98%

Evidence for Effective Multiple K+-Current Inhibitions by Tolvaptan, a Non-peptide Antagonist of Vasopressin V2 Receptor

Chang

Chan

et al. 2019

Front. Pharmacol.

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Tolvaptan (TLV), an oral non-peptide antagonist of vasopressin V 2 receptor, has been increasingly used for managements in patients with hyponatremia and/or syndrome of inappropriate antidiuretic hormone secretion. However, none of the studies have thus far been investigated with regard to its possible perturbations on membrane ion currents in endocrine or neuroendocrine cells. In our electrophysiological study, the whole-cell current recordings showed that the presence of TLV effectively and differentially suppressed the amplitude of delayed rectifier K + ( I K(DR) ) and M-type K + current ( I K(M) ) in pituitary GH 3 cells with an IC 50 value of 6.42 and 1.91 μM, respectively. This compound was also capable of shifting the steady-state activation curve of I K(M) to less depolarized potential without any appreciable change in the gating charge of this current. TLV at a concentration greater than 10 μM also suppressed the amplitude of erg -mediated K + current or the activity of large-conductance Ca 2+ -activated K + channels; however, this compound failed to alter the amplitude of hyperpolarization-activated cation current in GH 3 cells. In vasopressin-preincubated GH 3 cells, TLV-mediated suppression of I K(M) remained little altered. Under current-clamp condition, we also observed that addition of TLV increased the firing of spontaneous action potentials in GH 3 cells and further addition of flupirtine could reverse TLV-mediated elevation of the firing. In Madin-Darby canine kidney (MDCK) cells, the K + current elicited by long ramp pulse was also effectively subject to inhibition by this compound. Findings from the present study were thus stated as saying that the suppression by TLV of multiple type K + currents could be direct and independent of its antagonism of vasopressin V 2 receptors. Our study also reveals an important aspect that should be considered when assessing aquaretic effect of TLV or its structurally similar compounds.

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Section: Discussionmentioning

confidence: 98%

Evidence for Effective Multiple K+-Current Inhibitions by Tolvaptan, a Non-peptide Antagonist of Vasopressin V2 Receptor

Chang

Chan

et al. 2019

Front. Pharmacol.

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“…Urine AQP2, urine osmolality change and serum TLV concentration can be predictors for TLV e cacy in heart failure 18,24,25 . However, these measurements did not correlate with urine output change and weight loss in our study despite detected urine AQP2, the reduction of urine osmolality and elevated TLV concentration.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of tolvaptan on nephrotic patients with diuretic-resistant edema: a pilot study

Matsuura

Ohtake

Mochida

et al. 2020

Preprint

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Background Tolvaptan (TLV), a vasopressin type 2 receptor antagonist, is an effective drug for heart failure without worsening renal function. However, the effect of TLV on nephrotic syndrome remains unknown. This study aims to assess the association between response to TLV and clinical parameters including pathological evaluation in nephrotic patients with diuretics-resistance.Methods For prospectively enrolled patients, TLV was added for 14 days after renal biopsy performed. We evaluated the effect of TLV on urine output (UO) and body weight (BW) and the correlation of UO change with BW, urine and blood measurements and pathological evaluation. Pathological evaluation included glomerular sclerosis, tubulointerstitial injury, interstitial fibrosis and the degree of aquaporin 2 (AQP2) positivity in collecting ducts.Results Ten nephrotic patients were enrolled. Two patients already received 140 and 160mg furosemide and others 40mg furosemide before TLV. After TLV administration, no patients showed worsening renal function or hypernatremia (>145 mEq/L) and two patients without any improvement of symptoms discontinued the trial. TLV significantly increased UO at day 1 and decreased BW overall. UO increase at day 1 was significantly correlated with BW decrease at the last follow-up. UO increase at day 1 was correlated only with AQP2 positivity in collecting ducts on biopsied kidney (r2=0.59, p=0.01) while other urine and blood measurements were not. Conclusions TLV was effective on nephrotic patients. UO increase by TLV was correlated with AQP2 positivity in the collecting ducts while biochemistry in urine and blood was not.

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Decompensated Heart Failure and Renal Failure: What Is the Current Evidence?

Bielecka‐Dąbrowa

Godoy

Schefold

et al. 2018

Curr Heart Fail Rep

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One of the strongest predictors of adverse outcomes in ADHF is renal dysfunction, referred to as cardiorenal syndromes (CRS) or cardiorenal interactions. Patients with ADHF frequently develop worsening of renal function (WRF) and/or acute kidney injury (AKI). Recent studies brought new information about biomarkers in diagnosing and predicting prognosis of CRS. Among others, dry weight at hospital discharge is considered a surrogate marker of successful treatment in ADHF patients with/without renal dysfunction. The etiology of WRF appears to be an important factor for determining risk related to WRF as well as clinical management. The hypertonic saline used as adjunctive therapy for intravenous loop diuretics and/or induction of aquaresis (e.g., using tolvaptan) may be promising and efficient approaches in the future.

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Association between plasma concentration of tolvaptan and urine volume in acute decompensated heart failure patients with fluid overload

Cited by 3 publications

References 18 publications

Evidence for Effective Multiple K+-Current Inhibitions by Tolvaptan, a Non-peptide Antagonist of Vasopressin V2 Receptor

Evidence for Effective Multiple K+-Current Inhibitions by Tolvaptan, a Non-peptide Antagonist of Vasopressin V2 Receptor

Efficacy of tolvaptan on nephrotic patients with diuretic-resistant edema: a pilot study

Decompensated Heart Failure and Renal Failure: What Is the Current Evidence?

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