Fecal ammonium in mice with CKD: gastrointestinal sequestration by sodium zirconium cyclosilicate.

IF 3.7 2区 医学 Q1 PHYSIOLOGY
Fernando Marmol, Mohammed Badaruddin, Athar Baig, Minghao Ye, Jan Wysocki, Ebrahim Tahaei, Paul Welling, Krister Bamberg, Daniel Batlle
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引用次数: 1

Abstract

Urinary [Formula: see text] excretion is decreased in chronic kidney disease (CKD), but very little is known about fecal [Formula: see text] excretion. Sodium zirconium cyclosilicate (SZC) is a cation exchanger that selectively captures K+ in the gastrointestinal tract. We investigated if SZC can sequester [Formula: see text] in vivo and evaluated the effect of SZC on fecal [Formula: see text] in a mouse model of CKD. Mice with CKD induced by 5/6 kidney ablation were fed either a regular diet or a diet containing SZC (4 g/kg) and followed for 7 days. Fecal [Formula: see text] was measured before and after the addition of 50 meq KCl/L to release [Formula: see text] from SZC. [Formula: see text] sequestered in SZC in the gastrointestinal (GI) tract was estimated from the change in fecal [Formula: see text] observed when KCl was added to liberate the sequestered [Formula: see text]. In mice with CKD, fecal [Formula: see text] excretion was higher than in normal mice and also higher than urine [Formula: see text] excretion measured concurrently. Using data pooled from the SZC diet, the change in [Formula: see text] was 6.5 ± 0.6 compared with 0.6 ± 0.6 µmol/g on the normal diet (P < 0.0001). In conclusion, fecal [Formula: see text] excretion in CKD is increased and about sixfold higher than urine [Formula: see text] excretion, revealing an important route of elimination of [Formula: see text] present in the GI tract. SZC administration sequesters a substantial portion of [Formula: see text] in the GI tract, suggesting that the binding of [Formula: see text] offers therapeutic potential beyond its known primary action as a specific K+ binder.NEW & NOTEWORTHY Fecal [Formula: see text] excretion in chronic kidney disease is increased and about sixfold higher than urine [Formula: see text] excretion, revealing an important route of elimination of [Formula: see text] that is present in the gastrointestinal tract. Sodium zirconium cyclosilicate (SZC) administration sequesters a substantial portion of [Formula: see text], suggesting that binding of [Formula: see text] by SZC in the gastrointestinal tract offers therapeutic potential in chronic kidney disease and other clinical conditions beyond its known primary action of SZC as a specific K+ binder.

环硅酸锆钠对慢性肾病小鼠粪便铵的胃肠道隔离作用。
慢性肾脏疾病(CKD)患者尿排泄减少,但对粪便排泄却知之甚少。环硅酸锆钠(SZC)是一种阳离子交换剂,可选择性捕获胃肠道中的K+。我们研究了SZC是否能在体内隔离[公式:见文],并在CKD小鼠模型中评估了SZC对粪便[公式:见文]的影响。5/6肾消融所致CKD小鼠分别饲喂常规饮食和含SZC (4 g/kg)饮食,随访7 d。在SZC中加入50 meq KCl/L以释放[公式:见文]前后测定粪便[公式:见文]。[公式:见文]通过添加KCl来释放被隔离的[公式:见文]时粪便[公式:见文]的变化来估计胃肠道中SZC的隔离。在CKD小鼠中,粪便排泄量高于正常小鼠,同时也高于尿液排泄量。使用SZC日粮的数据,与正常日粮的0.6±0.6µmol/g相比,[公式:见文]的变化为6.5±0.6µmol/g (P < 0.0001)。总之,慢性肾病患者的粪便排泄增加,比尿排泄高出约6倍,揭示了存在于胃肠道中的排泄的重要途径。SZC在胃肠道中隔离了相当一部分[公式:见文],这表明[公式:见文]的结合提供了治疗潜力,超出了其已知的作为特定K+结合剂的主要作用。新的和值得注意的是,慢性肾脏疾病的粪便排泄增加,大约是尿液排泄的六倍,揭示了胃肠道中存在的[公式:见文]消除的重要途径。给予环硅酸锆钠(SZC)可隔离相当一部分[公式:见文],这表明SZC在胃肠道中的结合[公式:见文]具有治疗慢性肾脏疾病和其他临床疾病的潜力,超出了SZC作为特异性K+结合剂的已知主要作用。
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来源期刊
CiteScore
8.40
自引率
7.10%
发文量
154
审稿时长
2-4 weeks
期刊介绍: The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.
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