Effects of the Potassium-Binding Polymer Patiromer on Markers of Mineral Metabolism

Abstract

Background and objectives: Patiromer is a sodium-free, nonabsorbed, potassium-binding polymer that uses calcium as the counter-exchange ion and is approved for treatment of hyperkalemia. The 4-week TOURMALINE study in patients with hyperkalemia previously demonstrated that patiromer administered once daily reduces serum potassium similarly when given with or without food. We report a prespecified exploratory efficacy analysis as well as a post hoc efficacy and safety analysis of the TOURMALINE study on circulating markers of mineral metabolism.

Design, setting, participants, & measurements: Adults with hyperkalemia (potassium >5.0 mEq/L) were randomized to once-daily patiromer 8.4 g without/with food for 4 weeks, with doses adjusted to achieve and maintain serum potassium 3.8-5.0 mEq/L. Baseline and week 4 serum and 24-hour urine markers of mineral metabolism are reported for all patients combined (evaluable for efficacy, n=112; evaluable for safety, n=113). P values were calculated using a paired t test for change from baseline, unless otherwise specified.

Results: Mean (SD) baseline eGFR was 41±26 ml/min per 1.73 m². Mean (SD) changes from baseline to week 4 were 0.0±0.5 mg/dl (P=0.78; n=100) for albumin-corrected serum calcium, -0.2±0.2 mg/dl (P<0.001; n=100) for serum magnesium, and -0.1±0.7 mg/dl (P=0.47; n=100) for serum phosphate. Median (quartile 1, quartile 3) changes in 24-hour creatinine-normalized urine calcium and phosphate from baseline to week 4 were 2.5 (-11.5, 23.7) mg/24 h (P=0.10; n=69) and -43.0 (-162.6, 35.7) mg/24 h (P=0.004; n=95), respectively. Median (quartile 1, quartile 3) changes in intact parathyroid hormone and 1,25-dihydroxyvitamin D from baseline to week 4 were -13 (-31, 4) pg/ml (P<0.001; n=97) and -2 (-9, 3) pg/ml (P=0.05; n=96), respectively. There were no changes in fibroblast growth factor-23 or 25-hydroxyvitamin D. In patients (n=16) with baseline serum phosphate >4.8 mg/dL, the mean (SD) changes in serum and 24-hour creatinine-normalized urine phosphate from baseline to Week 4 were -0.6±0.8 mg/dl (n=13) and -149.1±162.6 mg/24hr (n=9), respectively.

Conclusions: Patiromer lowered urine phosphate in all patients, and lowered both serum and urine phosphate in a small subset of patients with hyperphosphatemia. Intact parathyroid hormone and 1,25-dihydroxyvitamin D decreased, with no change in serum calcium.

Keywords: 25-hydroxyvitamin D; Albumins; Calcifediol; Fibroblast Growth Factors; Hyperkalemia; Magnesium; Minerals; Phosphates; Polymers; Sodium; Vitamin D; creatinine; fibroblast growth factor 23; mineral metabolism; parathyroid hormone; patiromer; potassium.

Graphical abstract

Figure 1.

Mean serum levels of potassium, magnesium, serum albumin-corrected calcium, and phosphate over time. All values are mean±SD; shaded boxes represent target range for each electrolyte. *P<0.001; ^†P<0.05. BL, baseline.

Figure 2.

Mean 24-hour creatinine-normalized urine calcium and urine phosphate at baseline and week 4. Bars represent one-sided SD. Values above bars are mean (SD). Observed cases, no imputation.

Figure 3.

Median values for serum markers of mineral metabolism at baseline and week 4. Boxes represent median (center line), Q1 (lower bound), and Q3 (upper bound). Whiskers represent minimum and maximum values. Observed cases, no imputation. Max, maximum.