Patiromer induces rapid and sustained potassium lowering in patients with chronic kidney disease and hyperkalemia

Abstract

Patients with chronic kidney disease (CKD) have a high risk of hyperkalemia, which increases mortality and can lead to renin-angiotensin-aldosterone system inhibitor (RAASi) dose reduction or discontinuation. Patiromer, a nonabsorbed potassium binder, has been shown to normalize serum potassium in patients with CKD and hyperkalemia on RAASi. Here, patiromer's onset of action was determined in patients with CKD and hyperkalemia taking at least one RAASi. After a 3-day potassium- and sodium-restricted diet in an inpatient research unit, those with sustained hyperkalemia (serum potassium 5.5 - under 6.5 mEq/l) received patiromer 8.4 g/dose with morning and evening meals for a total of four doses. Serum potassium was assessed at baseline (0 h), 4 h postdose, then every 2-4 h to 48 h, at 58 h, and during outpatient follow-up. Mean baseline serum potassium was 5.93 mEq/l and was significantly reduced by 7 h after the first dose and at all subsequent times through 48 h. Significantly, mean serum potassium under 5.5 mEq/l was achieved within 20 h. At 48 h (14 h after last dose), there was a significant mean reduction of 0.75 mEq/l. Serum potassium did not increase before the next dose or for 24 h after the last dose. Patiromer was well tolerated, without serious adverse events and no withdrawals. The most common gastrointestinal adverse event was mild constipation in two patients. No hypokalemia (serum potassium under 3.5 mEq/l) was observed. Thus, patiromer induced an early and sustained reduction in serum potassium and was well tolerated in patients with CKD and sustained hyperkalemia on RAASis.

Figure 1

Patient disposition. BID, twice daily; K⁺, potassium.

Figure 2

Observed serum potassium (mEq/l) over time. Data presented as median (quartiles 25%, 75%), mean (s.e.). K⁺, potassium; s.e., standard error.

Figure 3

Proportion of patients achieving serum potassium within the normal range (3.8–5.0 mEq/l). *Twelve (40%) patients had serum potassium values slightly above 5.5 mEq/l (i.e., 5.6 mEq/l) at 10 h, just before the second dose. BL, baseline; K⁺, potassium.

Figure 4

Time to first serum potassium ⩽5.5 mEq/l. Patients whose change in serum potassium did not meet this threshold were censored at their last assessment time point. K⁺, potassium.

Figure 5

Study design. *A sequential testing procedure was used to determine the earliest time point at which the change from baseline in serum potassium was significant. Starting at 48 h, each time point was tested in order of reverse chronology (i.e., 48, 44, 41, 38 h, etc.), with the preceding time point assessed only if the change from baseline in serum potassium for the previously examined time point was statistically significantly. ^†Patients with serum potassium 5.5 to <6.5 mEq/l after the 3-day low-potassium, low-sodium diet run-in entered the treatment phase. BID, twice daily; CRU, clinical research unit; K⁺, potassium; Na⁺, sodium.