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

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.