Lingyun Li, Jeff Budden, Carol Moreno Quinn, David Bushinsky
{"title":"Effects of Patiromer and Sodium Zirconium Cyclosilicate on Blood Pressure in Rats with Chronic Kidney Disease.","authors":"Lingyun Li, Jeff Budden, Carol Moreno Quinn, David Bushinsky","doi":"10.1177/10742484241227580","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>p</i> < 0.001), with no difference in sBP between vehicle and SZC (<i>p</i> = 0.08). Similar results were observed for diastolic BP. Serum potassium levels fell with SZC (<i>p</i> < 0.02), but not vehicle or patiromer. Urine potassium decreased with both patiromer and SZC versus vehicle (<i>p</i> < 0.01); urine sodium increased with SZC (<i>p</i> < 0.01); and urine calcium increased with patiromer (<i>p</i> < 0.01). Urine phosphorus decreased with patiromer (<i>p</i> < 0.01) but increased with SZC (<i>p</i> < 0.01). Patiromer resulted in less proteinuria than vehicle or SZC (both p < 0.017).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"29 ","pages":"10742484241227580"},"PeriodicalIF":4.6000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/10742484241227580","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Methods: 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.
Results: 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 p < 0.001), with no difference in sBP between vehicle and SZC (p = 0.08). Similar results were observed for diastolic BP. Serum potassium levels fell with SZC (p < 0.02), but not vehicle or patiromer. Urine potassium decreased with both patiromer and SZC versus vehicle (p < 0.01); urine sodium increased with SZC (p < 0.01); and urine calcium increased with patiromer (p < 0.01). Urine phosphorus decreased with patiromer (p < 0.01) but increased with SZC (p < 0.01). Patiromer resulted in less proteinuria than vehicle or SZC (both p < 0.017).
Conclusions: 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.
背景:钾疏导剂帕替洛尔和环硅酸锆钠(SZC)被批准用于治疗慢性肾脏病(CKD)中经常出现的高钾血症。血压(BP)升高在慢性肾脏病中很常见,部分原因是钠排泄功能受损。我们在 CKD 大鼠模型中评估了帕替洛尔(可将钙换成钾)和 SZC(可将钠或氢换成钾)对血压的影响:方法:将36只5/6肾切除的Sprague Dawley大鼠随机分为三组(n = 12/组),接受4克/公斤/天的帕替洛尔或SZC或药物治疗,为期8周。通过放射性遥测测量血压,并测量尿蛋白和电解质:第 8 周时,所有组的收缩压(sBP)均有所升高;然而,帕替洛尔导致的 sBP 平均值(标准偏差)低于药物或 SZC(分别为 141 [2.9] vs 158 [5.2] 或 162 [6.1] mm Hg,均 p p = 0.08)。舒张压也观察到类似的结果。使用 SZC 后,血清钾水平下降(p p p p p p p 结论):帕替洛尔治疗 8 周后,大鼠的血压低于药物或 SZC。需要进一步研究确定钾结合剂对大鼠血压产生不同影响的机制。