Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.
Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Am J Physiol Renal Physiol. 2023 May 1;324(5):F464-F471. doi: 10.1152/ajprenal.00312.2022. Epub 2023 Apr 6.
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 ( < 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. 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.
尿[公式：见正文]排泄在慢性肾脏病（CKD）中减少，但对粪便[公式：见正文]排泄知之甚少。硅酸锆钠（SZC）是一种阳离子交换剂，可在胃肠道中选择性捕获 K。我们研究了 SZC 是否可以在体内捕获[公式：见正文]，并在 CKD 小鼠模型中评估了 SZC 对粪便[公式：见正文]的影响。通过 5/6 肾切除术诱导 CKD 的小鼠分别喂食常规饮食或含有 SZC（4 g/kg）的饮食，并在 7 天内进行跟踪。在向 SZC 中加入 50 meq KCl/L 以释放[公式：见正文]之前和之后，测量粪便[公式：见正文]。从向 SZC 中加入 KCl 以释放被捕获的[公式：见正文]时观察到的粪便[公式：见正文]变化中估算出胃肠道（GI）中被 SZC 捕获的[公式：见正文]。在 CKD 小鼠中，粪便[公式：见正文]排泄量高于正常小鼠，也高于同时测量的尿[公式：见正文]排泄量。使用来自 SZC 饮食的数据进行汇总，与正常饮食相比，[公式：见正文]的变化为 6.5±0.6，而 0.6±0.6 µmol/g（<0.0001）。总之，CKD 中的粪便[公式：见正文]排泄增加，约为尿[公式：见正文]排泄的六倍，这揭示了胃肠道中存在的[公式：见正文]的一个重要排泄途径。SZC 给药会将大量的[公式：见正文]捕获在胃肠道中，这表明[公式：见正文]的结合除了其作为特定 K 结合剂的已知主要作用之外，还具有治疗潜力。慢性肾脏病患者的粪便[公式：见正文]排泄增加，约为尿[公式：见正文]排泄的六倍，这揭示了胃肠道中存在的[公式：见正文]的一个重要排泄途径。硅酸锆钠（SZC）给药会将大量的[公式：见正文]捕获在胃肠道中，这表明 SZC 在胃肠道中与[公式：见正文]的结合除了其作为特定 K 结合剂的已知主要作用之外，在慢性肾脏病和其他临床情况下具有治疗潜力。
