Division of Nephrology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.
Clinical Development.
Clin J Am Soc Nephrol. 2019 Jan 7;14(1):103-110. doi: 10.2215/CJN.04500418. Epub 2018 Oct 31.
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 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, =112; evaluable for safety, =113). values were calculated using a paired test for change from baseline, unless otherwise specified.
Mean (SD) baseline eGFR was 41±26 ml/min per 1.73 m. Mean (SD) changes from baseline to week 4 were 0.0±0.5 mg/dl (=0.78; =100) for albumin-corrected serum calcium, -0.2±0.2 mg/dl (<0.001; =100) for serum magnesium, and -0.1±0.7 mg/dl (=0.47; =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 (=0.10; =69) and -43.0 (-162.6, 35.7) mg/24 h (=0.004; =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 (<0.001; =97) and -2 (-9, 3) pg/ml (=0.05; =96), respectively. There were no changes in fibroblast growth factor-23 or 25-hydroxyvitamin D. In patients (=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 (=13) and -149.1±162.6 mg/24hr (=9), respectively.
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.
聚对苯二甲酸丁二醇酯是一种不含钠、不被吸收、与钾结合的聚合物，使用钙作为反离子交换，已被批准用于治疗高钾血症。此前一项为期 4 周的高钾血症患者 TOURMALINE 研究表明，聚对苯二甲酸丁二醇酯每日一次给药，无论是否与食物同服，均可降低血清钾水平。我们报告了一项预先指定的探索性疗效分析，以及 TOURMALINE 研究中关于循环矿物质代谢标志物的疗效和安全性分析。
设计、地点、参与者和测量：患有高钾血症（血钾>5.0 mEq/L）的成年人被随机分为每日一次聚对苯二甲酸丁二醇酯 8.4 g 不/与食物同服 4 周，剂量调整以达到并维持血清钾 3.8-5.0 mEq/L。报告了所有患者（疗效评估=112；安全性评估=113）的基线和第 4 周血清和 24 小时尿液矿物质代谢标志物。除非另有说明，否则使用配对 t 检验计算从基线到第 4 周的变化值。
平均（SD）基线 eGFR 为 41±26 ml/min/1.73 m。与基线相比，第 4 周的平均（SD）变化为 0.0±0.5 mg/dl（=0.78；=100）为校正白蛋白的血清钙，-0.2±0.2 mg/dl（<0.001；=100）为血清镁，-0.1±0.7 mg/dl（=0.47；=100）为血清磷酸盐。从基线到第 4 周，24 小时肌酐标准化尿钙和尿磷的中位数（四分位距 1，四分位距 3）变化分别为 2.5（-11.5，23.7）mg/24 h（=0.10；=69）和-43.0（-162.6，35.7）mg/24 h（=0.004；=95）。从基线到第 4 周，完整甲状旁腺激素和 1,25-二羟维生素 D 的中位数（四分位距 1，四分位距 3）变化分别为-13（-31，4）pg/ml（<0.001；=97）和-2（-9，3）pg/ml（=0.05；=96）。成纤维细胞生长因子-23 和 25-羟维生素 D 无变化。在基线血清磷>4.8 mg/dL 的患者（=16）中，第 4 周血清和 24 小时肌酐标准化尿磷的平均（SD）变化分别为-0.6±0.8 mg/dl（=13）和-149.1±162.6 mg/24 h（=9）。
聚对苯二甲酸丁二醇酯降低了所有患者的尿磷，在一小部分高磷血症患者中降低了血清和尿磷。完整甲状旁腺激素和 1,25-二羟维生素 D 下降，血清钙无变化。
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