A new study recently published in the journal JAMA revealed that patiromer therapy offers long-term clinical benefits for patients suffering from kidney disease and related hyperkalemia. The study is entitled “Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial”. The study was funded by Relypsa Inc., the manufacturer of patiromer, and conducted by researchers at several universities and hospitals in the United States.
Chronic kidney disease (CKD) is a medical condition characterized by the gradual loss of kidney function over time. The condition can eventually lead to kidney failure, a situation in which the patient will have to undergo either dialysis or a kidney transplant. CKD can be caused by disorders like diabetes or high blood pressure. The disease is associated with an increased risk of cardiovascular diseases, with heart disease accounting for the major cause of death in CKD patients. It is estimated that 26 million American adults suffer from the disease.
CKD has been linked to a potentially life-threatening complication known as hyperkalemia, which refers to abnormally high potassium levels in the blood (above 5 millimoles per liter). Patients who are most at risk are those with CKD combined with diabetes and hypertension or heart failure, or under prolonged CKD treatment with renin-angiotensin-aldosterase system (RAAS) inhibitors. Hyperkalemia can lead to cardiac arrhythmia and sudden death.
Patiromer is a drug with a high capacity to bind to free potassium, so that the excess of this ion can be excreted from the body. In the study, researchers evaluated the long-term safety and efficacy of patiromer in patients with hyperkalemia.
The team conducted a randomized, multicenter, dose-ranging Phase 2 clinical trial (AMETHYST-DN; NCT01371747) at 48 sites in Europe between June 2011 and June 2013. In total, 306 patients (mean age of 66.3 years) with CKD, hyperkalemia, hypertension and type 2 diabetes were analyzed. All patients received standard treatment for CKD with RAAS inhibitors prior to and during the trial. Patients were classified according to their baseline serum potassium levels into mild (5.0 to 5.5 mmol/L; 222 patients) or moderate (greater than 5.5 mmol/L; 84 patients) hyperkalemia groups. Patiromer was tested in three different doses: 4.2 g, 8.4 g or 12.6 g in patients with mild hyperkalemia, and 8.4 g, 12.6 g or 16.8 g in patients with moderate hyperkalemia. All doses were administered twice daily and patients were followed-up for a period of 52 weeks.
Researchers found that the serum potassium levels after four weeks of treatment had decreased in all patients and dose regimens evaluated, especially in patients with moderate hyperkalemia. Furthermore, the average potassium levels consistently decreased over the 52 week period of the trial, with 80% of the patients having normal potassium levels (between 3.5 and 5) at the end of the study. Interestingly, the team reported that when patients stopped patiromer treatment, the serum potassium levels increased and hyperkalemia recurred within eight weeks.
“This is a significant advance, a huge deal,” said the study’s lead author Dr. George Bakris from the University of Chicago Medicine in a news release. According to the author, CKD “affects everyone with stage 4 or 5 chronic kidney disease, almost 1 million people in the United States.”
In terms of adverse events over the 52 weeks of treatment, the most common ones reported were hypomagnesemia (7.2%; magnesium deficiency), mild to moderate constipation (6.3%) and hypokalemia (5.6%).
“Patiromer consistently maintained normal serum potassium levels over 52 weeks,” concluded the research team. There was “high adherence, low risk of hypokalemia (low potassium levels) and minimal discontinuation because of adverse events.”
The authors concluded that in this cohort of patients with hyperkalemia and diabetic kidney disease, patiromer at a dose of 4.2 to 16.8 g twice daily was able to significantly decrease the serum potassium levels to the normal range at four weeks into treatment; an effect that lasted through the 52 weeks of the study. The team believes that patiromer, through the control of potassium levels, can prevent life-threatening adverse events.
“An effective treatment for hyperkalemia lets us reconsider clinical trials in more advanced kidney disease that were stopped, or never started, due to risk of hyperkalemia,” concluded Dr. Bakris.