CSL Vifor, Redwood City, CA, USA.
Global Medical Lead, Medical Affairs, CSL Vifor, Glattbrugg, Switzerland.
J Cardiovasc Pharmacol Ther. 2024 Jan-Dec;29:10742484241227580. doi: 10.1177/10742484241227580.
Potassium-binders patiromer and sodium zirconium cyclosilicate (SZC) are approved to treat hyperkalaemia, which is frequently observed in chronic kidney disease (CKD). Elevated blood pressure (BP) is common in CKD, due in part to impaired sodium excretion. The effect of patiromer, which exchanges calcium for potassium and SZC, which exchanges sodium or hydrogen for potassium, on BP was assessed in a CKD rat model.
Thirty-six Sprague Dawley rats with 5/6 nephrectomy were randomised to three groups (n = 12/group) to receive 4 g/kg/day patiromer or SZC, or vehicle treatment, for 8 weeks. BP was determined by radiotelemetry and urinary protein and electrolytes were measured.
At Week 8, systolic BP (sBP) increased in all groups; however, patiromer led to a lower mean (standard deviation) sBP than vehicle or SZC (141 [2.9] vs 158 [5.2] or 162 [6.1] mm Hg, respectively, both < 0.001), with no difference in sBP between vehicle and SZC ( = 0.08). Similar results were observed for diastolic BP. Serum potassium levels fell with SZC ( < 0.02), but not vehicle or patiromer. Urine potassium decreased with both patiromer and SZC versus vehicle ( < 0.01); urine sodium increased with SZC ( < 0.01); and urine calcium increased with patiromer ( < 0.01). Urine phosphorus decreased with patiromer ( < 0.01) but increased with SZC ( < 0.01). Patiromer resulted in less proteinuria than vehicle or SZC (both p < 0.017).
After 8 weeks, treatment with patiromer resulted in lower BP in rats than vehicle or SZC. Further studies are needed to determine the mechanism of the differential effect of potassium binders on rat BP.
聚卡波非钙和硅酸锆钠(SZC)被批准用于治疗高钾血症,高钾血症在慢性肾脏病(CKD)中很常见。部分由于钠排泄受损,CKD 中常伴有血压升高。评估了聚卡波非钙(交换钙和钾)和 SZC(交换钠或氢和钾)对 CKD 大鼠模型血压的影响。
36 只 5/6 肾切除术 Sprague Dawley 大鼠随机分为 3 组(每组 n=12),接受 4g/kg/天聚卡波非钙或 SZC 或载体治疗 8 周。通过无线电遥测法测定血压,测量尿蛋白和电解质。
第 8 周时,所有组的收缩压(sBP)均升高;然而,与载体或 SZC 相比,聚卡波非钙导致平均(标准差)sBP 更低(141[2.9]与 158[5.2]或 162[6.1]mmHg,均<0.001),载体和 SZC 之间的 sBP 无差异(=0.08)。舒张压也观察到类似的结果。SZC 导致血清钾水平下降(<0.02),但载体或聚卡波非钙没有。与载体相比,聚卡波非钙和 SZC 均导致尿钾减少(均<0.01);SZC 导致尿钠增加(<0.01);聚卡波非钙导致尿钙增加(<0.01)。聚卡波非钙导致尿磷减少(<0.01),但 SZC 导致尿磷增加(<0.01)。与载体或 SZC 相比,聚卡波非钙导致蛋白尿减少(均<0.017)。
8 周后,与载体或 SZC 相比,聚卡波非钙治疗可使大鼠血压降低。需要进一步的研究来确定钾结合剂对大鼠血压的不同影响的机制。