Sodium zirconium cyclosilicate and roxadustat: Novel treatment options for hyperkalaemia and anaemia in CKD
Studies on the inorganic compound sodium zirconium cyclosilicate and the hypoxia inducible factor prolyl hydroxylase (HIF-PH) pathway inhibitor roxadustat have shown efficacy and safety for the management of hyperkalaemia and anaemia, respectively, among chronic kidney disease (CKD) patients.
“Clinical trials showed that hyperkalaemic CKD patients treated with sodium zirconium cyclosilicate were able to maintain normokalaemia for over 2 weeks, with only mild gastrointestinal [GI] adverse effects [AE]. Roxadustat is a new agent that stimulates erythropoietin [EPO] synthesis, resulting in durable and stable haemoglobin response in anemic CKD patients,” said Professor Sydney Tang of the Department of Medicine, The University of Hong Kong (HKU).
A phase II study in 90 participants (mean serum potassium level, 5.1 mEq/L) demostrated a notable decrease in potassium levels from baseline 2 hours after commencement of therapy in those treated with the sodium zirconium silicate crystal compound, ZS-9 10 g, vs placebo (−0.13 ± 0.35 vs −0.02 ± 0.34). [Kidney Int 2015;88:404-411]
“There was also a significant decline in 24-hour urinary potassium excretion in the ZS-9 group relative to placebo [−15.8 mEq/24 hour, p<0.001] at day 2,” Tang said.
The HARMONIZE study (n=258) showed a significant reduction of serum potassium levels in 2 days in 98 percent of patients treated with ZS-9, with durability of the effect over 2 weeks. [JAMA 2014;312:2223-2233]
“Treatment with ZS-9 showed no dose-related effects on serum glucose, blood pressure and heart rate, with only mild-to-moderate GI AEs such as diarrhoea experienced by patients who received treatment,” he added.
“HIF-PH inhibitors target a pathway that results in improvement of endogenous EPO synthesis. Other effects of treatment with HIF-PH inhibitors include increase in intestinal iron absorption, upregulation of EPO and transferrin receptors, and formation of fully functional mature erythrocytes,” Tang explained. [Am J Kidney Dis 2017;69:815-826]
“The first-in-class HIF-PH inhibitor roxadustat is able to achieve target haemoglobin levels similar to physiologic adaptations to high altitude, blood loss and pulmonary oedema,” he added.
In two phase II studies conducted in China, haemoglobin increase of ≥1 g/dL from baseline was achieved in a higher percentage of non-dialysis dependent CKD patients (n=91) who received low-dose or high-dose roxadustat vs placebo (low dose, 80 percent; high dose, 87.1 percent; placebo, 23.3 percent; p<0.0001). [Nephrol Dial Transplant 2017;32:1373-1386]
Among dialysis-dependent patients (n=87), a significantly higher proportion of patients who received medium-dose or high-dose roxadustat maintained their haemoglobin levels after 5−6-weeks vs those who received epoetin alfa (88.9 percent, p=0.008; 100 percent, p=0.0003 vs 50 percent).
“In addition to that, patients treated with roxadustat experienced significant decreases in cholesterol and hepcidin levels. Hepcidin is a protein that promotes transport and utilization of iron in the peripheral tissues, providing additional benefit to CKD patients with anaemia,” explained Tang.