A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient.
A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient.
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DOI：
10.1038/ki.2014.382
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发表时间：
2015-08
影响因子：
19.6
通讯作者：
Rasmussen HS
中科院分区：
文献类型：
--
作者：
Ash SR;Singh B;Lavin PT;Stavros F;Rasmussen HS
高钾血症导致显著的死亡率，并限制了心脏保护性和肾脏保护性肾素-血管紧张素-醛固酮阻滞剂的使用。目前的疗法耐受性差，并不总是有效的。在这里，我们进行了一项2期随机、双盲、安慰剂对照的剂量递增研究，以评估ZS-9的安全性和有效性。这种口服选择性阳离子交换剂优先将钾截留在胃肠道中，在2天内给予稳定的3期慢性肾脏疾病和高钾血症（5.0 - 6.0 mEq/l）患者。在90名平均基线血清钾为5.1 mEq/l的合格患者中，30名患者被随机分配至安慰剂组、12-0.3 g、24-3 g或24至10 g的ZS-9组，每天三次，持续2天，规律饮食。没有退出，ZS-9剂量依赖性地降低血清钾。主要疗效终点（前48小时血清钾下降率）在3-和10-g队列中达到显著性。与基线相比，38 h时平均血清钾显著降低0.92±0.52 mEq/l。与安慰剂相比，10 g ZS-9组第2天的尿钾排泄量显著降低（每24小时+15.8 +/-21.8 mEq vs. +8.9 +/-22.9 mEq）。在这项短期研究中，未报告严重不良事件; 3 g剂量组中仅轻度便秘可能与治疗相关。因此，ZS-9在患有稳定的慢性肾病和高钾血症的患者中耐受良好，导致血清钾快速、持续降低。
Hyperkalemia contributes to significant mortality and limits the use of cardioprotective and renoprotective renin–angiotensin–aldosterone blockers. Current therapies are poorly tolerated and not always effective. Here we conducted a phase 2 randomized, double-blind, placebo-controlled dose-escalation study to assess safety and efficacy of ZS-9. This oral selective cation exchanger that preferentially entraps potassium in the gastrointestinal tract was given to patients with stable Stage 3 chronic kidney disease and hyperkalemia (5.0 to 6.0 mEq/l) during a 2-day period. Of 90 eligible patients with mean baseline serum potassium of 5.1 mEq/l, 30 were randomized to placebo, 12–0.3 g, 24–3 g, or 24 to 10 g of ZS-9 three times daily for 2 days with regular meals. None withdrew and ZS-9 dose-dependently reduced serum potassium. The primary efficacy end point (rate of serum potassium decline in the first 48 h) was met with significance in the 3- and 10-g cohorts. From baseline, mean serum potassium was significantly decreased by 0.92±0.52 mEq/l at 38 h. Urinary potassium excretion significantly decreased with 10-g ZS-9 as compared to placebo at day 2 (+15.8 +/− 21.8 vs. +8.9 +/− 22.9 mEq per 24h) from placebo at day 2. In this short-term study, no serious adverse events were reported; only mild constipation in the 3-g dose group was possibly related to treatment. Thus, ZS-9 was well-tolerated in patients with stable chronic kidney disease and hyperkalemia leading to a rapid, sustained reduction in serum potassium.