scholarly journals Effects of Chicory on Serum Uric Acid, Renal Function, and GLUT9 Expression in Hyperuricaemic Rats with Renal Injury and In Vitro Verification with Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yong-Nan Jin ◽  
Zhi-Jian Lin ◽  
Bing Zhang ◽  
Yun-Fei Bai
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Renal Dysfunction ◽  
Serum Uric Acid ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Serum Uric Acid Level ◽  
In Vivo Studies ◽  
Renal Tubules

Hyperuricaemia (HUA) is an independent risk factor for chronic kidney disease. Urate crystals are deposited in the kidney and can cause renal tubular interstitial fibrosis, leading to renal dysfunction. Chicory extract (hereafter referred to as chicory) clearly reduced serum uric acid levels in rats with HUA induced by 10% fructose. This is the first study to observe the effect of chicory on serum uric acid levels and renal function in rats with HUA and renal injury. In vivo studies using hyperuricaemic rats with renal injury induced by yeast and adenine demonstrated that chicory decreased serum uric acid level, and its effect of delaying the progression of kidney injury was better than that of benzbromarone. In vitro cell experiments showed that this effect is related to the inhibition of GLUT9 protein expression in renal tubules and that lowering blood uric acid concentrations is one of the factors that alleviates renal damage. The results of this study indicate that chicory can be used as an alternative for alleviating renal dysfunction in hyperuricaemia.

scholarly journals Comparative study of a novel selective urate reabsorption inhibitor “dotinurad” among patient groups with different stages of renal dysfunction

2021 ◽  
Author(s):  
Toshinari Takahashi ◽  
Takanobu Beppu ◽  
Yuji Hidaka ◽  
Tatsuo Hosoya
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Renal Dysfunction ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Patient Groups ◽  
Urate Reabsorption

Abstract Background Dotinurad is a selective urate reabsorption inhibitor (SURI), which selectively inhibits URAT1 to lower serum uric acid levels in patients with hyperuricemia. Herein, the effects of dotinurad were compared among patient groups with different stages of renal dysfunction. Methods Patient data from four clinical trials were pooled and divided into four groups according to the stage of renal dysfunction to compare the effects of dotinurad at different stages. The grouping (stages G1–G3b) was based on the estimated glomerular filtration rate (eGFR) of the patients. In addition, patient data from a long-term study (34 or 58 weeks) were evaluated in the same manner. Results In the pooled analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 64.7–100.0% at a dose of 2 or 4 mg. In the long-term analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 60.0–100.0% at a dose of 2 or 4 mg. Although the outcomes in stage G3b were worse due to higher baseline serum uric acid levels, satisfactory outcomes were observed in all stages. Even in stages G3a and G3b, when renal function declined, the eGFR remained constant throughout the dose period. Conclusion The efficacy of dotinurad was confirmed in hyperuricemic patients with normal renal function (stage G1) and mild to moderate renal dysfunction (stage G2–G3b). Dotinurad was found to be effective in the treatment of hyperuricemia in patients with mild to moderate renal dysfunction.

scholarly journals Effects of mild and moderate renal dysfunction on pharmacokinetics, pharmacodynamics, and safety of dotinurad: a novel selective urate reabsorption inhibitor

2019 ◽  
Vol 24 (S1) ◽  
pp. 17-24 ◽  
Author(s):  
Hiroyuki Fukase ◽  
Daisuke Okui ◽  
Tomomitsu Sasaki ◽  
Masahiko Fushimi ◽  
Tetsuo Ohashi ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Renal Dysfunction ◽  
Serum Uric Acid ◽  
Normal Renal Function ◽  
Reduction Rate ◽  
Significant Difference ◽  
Function Group ◽  
Urate Reabsorption ◽  
Renal Function Group

Abstract Background Dotinurad, a novel selective urate reabsorption inhibitor, exerts a serum uric acid-lowering effect by selectively inhibiting urate transporter 1 (URAT1) in patients with hyperuricemia. It is generally known that the progression of renal dysfunction is associated with a reduction in the serum uric acid-lowering effects of uricosuric drugs. We, therefore, investigated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of dotinurad in subjects with renal dysfunction. Methods This was a parallel-group, open-label, single-dose clinical pharmacology study. Dotinurad (1 mg) was administered once, orally to subjects with mild (estimated glomerular filtration rate [eGFR], ≥ 60 to < 90 mL/min/1.73 m2) or moderate (eGFR, ≥ 30 to < 60 mL/min/1.73 m2) renal dysfunction or normal (eGFR, ≥ 90 mL/min/1.73 m2) renal function. Results The time-course of mean plasma concentration of dotinurad had similar profiles across the groups. Regarding PK, there was no significant difference between the renal dysfunction groups and normal renal function group. Regarding PD, the maximum reduction rate in serum uric acid levels and the fractional uric acid excretion (FE) ratio (FE0–24/FE−24–0) were significantly lower in the moderate renal dysfunction group than in the normal renal function group. However, other PD parameters were not significantly different among the groups. No notable adverse events or adverse drug reactions were observed in this study. Conclusion These results suggested that no dose adjustment might be necessary when administering dotinurad to patients with mild-to-moderate renal dysfunction. ClinicalTrials.gov Identifier: NCT02347046.

U-shaped relationship between serum uric acid level and decline in renal function during a 10-year period in female subjects: BOREAS-CKD2

2020 ◽  
Vol 44 (1) ◽  
pp. 107-116 ◽  
Author(s):  
Kazuma Mori ◽  
Masato Furuhashi ◽  
Marenao Tanaka ◽  
Keita Numata ◽  
Takashi Hisasue ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Female Subjects

scholarly journals Serum Uric Acid Level, Longitudinal Blood Pressure, Renal Function, and Long-Term Mortality in Treated Hypertensive Patients

Hypertension ◽  
2013 ◽  
Vol 62 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Jesse Dawson ◽  
Panniyammakal Jeemon ◽  
Lucy Hetherington ◽  
Caitlin Judd ◽  
Claire Hastie ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Hypertensive Patients ◽  
Long Term Mortality

scholarly journals CONSTITUENT AND ANTIHYPERURICEMIC ACTIVITY OF STELECHOCARPUS BURAHOL LEAVES SUBFRACTIONS

2017 ◽  
Vol 10 (4) ◽  
pp. 435
Author(s):  
Titik Sunarni ◽  
Irda Fidrianny ◽  
Maria Immaculata Iwo ◽  
Komar Ruslan Wirasutisna
Keyword(s):  
Uric Acid ◽  
Ethyl Acetate ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Ethyl Acetate Fraction ◽  
Chemical Constituent

Objectives: The goal of this research was to evaluate antihyperuricemic activity of Stelechocarpus burahol leaves subfractions and isolate its chemical constituent of active subfraction.Methods: Ethyl acetate fraction from S. burahol extract was subfractionated by vacuum liquid chromatography and the active subfractions were further subfractionated by classic column chromatography using isocratic eluent followed by isolated the chemical constituent from active subfraction. Hyperuricemic rat model was induced by given  potassium oxonate  intraperitoneally. The inhibitory effect of subfractions on the xanthine oxidase (XO) activity was determined using UV-visible spectrophotometry method.Results: Subfraction E.3, E.4 and E.5 significantly (p<0.05) reduced the serum uric acid level 43, 46 and 33,9%, respectively. The E.3, E.4 and E.5 have very weak activity. Subfraction E.3.2 and E.4.3 significantly (p<0.05) reduced the serum uric acid level 29 and 38 % respectively, however still very weak effect on XO activity.  Chemical constituent which was isolated from E.4.3 subfraction was kaempferol-3-O-rhamnoside.Conclusion: The subfractions of ethyl acetate fraction had antihyperuricemic activity in vivo but less  effect on XO acitivity in vitro. Compound R in active antihyperuricemic of subfraction E.4.3 was kaempferol-3-O-rhamnosideKeyword: Stelechocarpus burahol, subfraction, antihyperuricemic, xanthin oxidase inhibitory activity, kaempferol-3-O-rhamnoside.  

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