Effects of Patiromer and Sodium Zirconium Cyclosilicate on Blood Pressure in Rats with Chronic Kidney Disease

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.

Advancing crush syndrome management: the potent role of Sodium zirconium cyclosilicate in early hyperkalemia intervention and survival enhancement in a rat model

“…The study of Li et al also indicates that SZC has a minimal impact on renal function. There were no statistically significant differences in serum Cre levels among the three treatment groups ( p > 0.05) ( Li et al, 2024 ). Current models of crush injury-related renal injury often use glycerol for intramuscular injection to construct a model of rhabdomyolysis as a substitute ( Belliere et al, 2015 ; Rosenkrans et al, 2020 ).…”