Clinical Pharmacology in Diuretic Use

Ellison, David H.

doi:10.2215/cjn.09630818

Cited by 126 publications

(100 citation statements)

References 83 publications

(70 reference statements)

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“…Spironolactone, an aldosterone antagonist, either alone or in combination with the loop diuretic (e.g., furosemide) is considered as the first-line treatment for management of patients with liver cirrhosis and persistent edema [ 4 ]. However, some patients are diuretic-resistant and might not respond adequately to this therapy [ 5 ], e.g., those with hypoalbuminemia show a poor response with furosemide [ 6 ]. Furthermore, randomly increasing the diuretic dose is restricted, owing to the risk of adverse drug reactions (ADRs), such as worsening of renal function, activation of the rennin–angiotensin and sympathetic nervous systems, electrolyte disturbances, and hepatic coma [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study)

et al. 2020

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Background This large-scale post-marketing surveillance study (START study) evaluated the effectiveness and safety of tolvaptan in Japanese liver cirrhosis patients with hepatic edema in real-world clinical settings. Here, we present the final analysis outcomes. Methods A prospective, multicenter, non-interventional study involving patients who received tolvaptan for the treatment of liver cirrhosis with hepatic edema with an insufficient response to conventional diuretics. The observation period was up to 6 months. Effectiveness evaluation included changes in body weight and clinical symptoms. Safety analysis included evaluation of adverse drug reactions (ADRs). Results Case reports of 1111 patients were collected. Of these, 1109 were included in the safety analysis and 1098 in the effectiveness analysis. The mean age was 69.4 ± 11.5 years and 695 (62.7%) patients were male. After tolvaptan treatment, a decrease in body weight from baseline was -2.6 ± 2.7 kg on day 7 and -3.8 ± 4.1 kg on day 14. Moreover, clinical symptoms significantly improved over the 14-day treatment. Frequently reported ADRs were thirst (6.6%), hepatic encephalopathy (2.3%), dehydration (1.5%), and hypernatremia (1.2%). A serum sodium level of C 150 mEq/L was reported in five patients (0.5%). Multivariate analyses showed that the baseline blood urea nitrogen (BUN) level (cut-off value: 22.4 mg/ dL) was the predictive factor for tolvaptan treatment response.Conclusions The results suggest that tolvaptan was effective and well-tolerated in liver cirrhosis patients with hepatic edema. In the real-world clinical setting, tolvaptan provides a useful option for the treatment of hepatic edema.

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Section: Introductionmentioning

confidence: 99%

Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study)

et al. 2020

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“…For instance, loop diuretics such as furosemide and bumetanide, inhibitors of the NKCC2 cotransporter, are among the most powerful antihypertensive drugs available to date. They act by increasing the volume of urine and the amount of excreted Na + and are widely used for the clinical management of hypertension and edema 2 . However, considering growing concerns raised about adverse effects of classic diuretics such as thiazides and loop www.nature.com/scientificreports www.nature.com/scientificreports/ diuretics 3 , the availability of new synthetic, semi-synthetic or natural-derived (herbs and botanicals) diuretics have attracted considerable attention.…”

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confidence: 99%

Role of PKC in the Regulation of the Human Kidney Chloride Channel ClC-Ka

Gerbino

Zio

Russo

et al. 2020

Sci Rep

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The physiological role of the renal ClC-Ka/ClC-K1 channels is to confer a high Cl- permeability to the thin Ascending Limb of Henle (tAL), which in turn is essential for establishing the high osmolarity of the renal medulla that drives water reabsorption from collecting ducts. Here, we investigated by whole-cell patch-clamp measurements on HEK293 cells co-expressing ClC-Ka (tagged with GFP) and the accessory subunit barttin (tagged with m-Cherry) the effect of a natural diuretic extract from roots of Dandelion (DRE), and other compounds activating PKC, such as ATP, on ClC-Ka activity and its membrane localization. Treatment with 400 µg/ml DRE significantly inhibited Cl- currents time-dependently within several minutes. Of note, the same effect on Cl- currents was obtained upon treatment with 100 µM ATP. Pretreatment of cells with either the intracellular Ca2+ chelator BAPTA-AM (30 μM) or the PKC inhibitor Calphostin C (100 nM) reduced the inhibitory effect of DRE. Conversely, 1 µM of phorbol meristate acetate (PMA), a specific PKC activator, mimicked the inhibitory effect of DRE on ClC-Ka. Finally, we found that pretreatment with 30 µM Heclin, an E3 ubiquitin ligase inhibitor, did not revert DRE-induced Cl- current inhibition. In agreement with this, live-cell confocal analysis showed that DRE treatment did not induce ClC-Ka internalization. In conclusion, we demonstrate for the first time that the activity of ClC-Ka in renal cells could be significantly inhibited by the activation of PKC elicited by classical maneuvers, such as activation of purinergic receptors, or by exposure to herbal extracts that activates a PKC-dependent pathway. Overall, we provide both new information regarding the regulation of ClC-Ka and a proof-of-concept study for the use of DRE as new diuretic.

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“…Another limitation attenuating effectiveness is post-diuretic sodium retention, from an increase in tubular avidity for sodium once the diuretic has been cleared. Adding to this complexity is the concern over bioavailability, gastrointestinal absorption rates, and renal handling of loop diuretics [Ellison 2019;Costanzo 2007]. The Heart Surgery Forum #2020-3127…”

Section: Discussionmentioning

confidence: 99%

Aquapheresis: An Institutional Experience

Khine

Lam

Dholakia

et al. 2020

HSF

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Background: Aquapheresis (AQ) consists of the extracorporeal extraction of plasma water from the vascular space across a semipermeable membrane in response to a transmembrane pressure gradient. The primary utilization of AQ has been in the management of patients with diuretic resistant heart failure with a treatment goal directed to quickly eliminate the excess fluid and optimize volume status. This modality is similar to isolated ultrafiltration performed on those patients requiring dialysis, but utilizes a machine that is smaller and easier to initiate and operate compared with traditional dialysis equipment. Method: A retrospective study that describes the indications in which AQ was utilized at Lenox Hill Hospital. The patient list was generated by searching for the keyword “Aquaph” in our electronic health record (EHR) orders. Patients were categorized based on hospital location and indication of AQ therapy. Additional information includes duration of treatment (days), changes in creatinine (start of AQ to stop of AQ), and total volume removed. Results: The search generated 28 patients; five were excluded as AQ was not initiated. In the remaining 23 patients, the mean aquapheretic volume per day was 1954 mls, with no significant change in creatinine. Indications for AQ broke out into five main categories: cardiogenic shock including post cardiothoracic procedure (10 pts); anasarca (5 pts); ATN with volume overload (4 pts); ESKD with bridge ultrafiltration between hemodialysis treatments (2 pts); and post-op volume overload (2 pts). Conclusion: We found that aquapheresis can be utilized in situations other than diuretic resistant heart failure. Also to consider, is the ease in which this less complicated aquapheresis equipment can be operated compared to the more complex hemodialysis equipment.

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Clinical Pharmacology in Diuretic Use

Cited by 126 publications

References 83 publications

Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study)

Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study)

Role of PKC in the Regulation of the Human Kidney Chloride Channel ClC-Ka

Aquapheresis: An Institutional Experience

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