Medicherla Satya, Reddy Guru, Gupta Pramod, Chertow Glenn M, Gupta Shalabh
Unicycive Therapeutics, Los Altos, California.
Division of Nephrology, Stanford University School of Medicine, Stanford, California.
Kidney360. 2025 Mar 1;6(3):361-368. doi: 10.34067/KID.0000000709. Epub 2025 Jan 22.
Combination therapy with oxylanthanum carbonate+tenapanor led to greater reductions in urinary phosphate excretion than either drug alone. We demonstrated dose-dependent and sizable reductions in urinary phosphate excretion in response to oxylanthanum carbonate monotherapy.
This study evaluated the combined effects of oxylanthanum carbonate (OLC), an investigational phosphate binder, and tenapanor, an approved sodium/hydrogen exchanger 3 inhibitor that reduces paracellular phosphate absorption, on urinary phosphate excretion in rats on a high-phosphorus diet.
Sixty-four male Sprague Dawley rats were randomized into eight groups: vehicle; tenapanor (0.15 mg/kg) only; OLC (0.75%, 1.5%, and 3%) only; and combination OLC (0.75%, 1.5%, and 3%)+tenapanor (0.15 mg/kg). Vehicle and tenapanor were dosed orally twice per day, whereas OLC was incorporated into diets. We collected 24-hour urine samples to measure urinary phosphate excretion, a proxy for intestinal phosphate absorption efficiency. Primary analyses compared pooled results in the three OLC dose groups.
In the tenapanor 0.15 mg/kg group, mean urinary phosphate excretion from days 9 to 11 was 8.5 mg/d (12.5%) lower compared with the vehicle group. In the OLC-alone groups, mean urinary phosphate excretion (pooled across the 0.75%, 1.5%, and 3% OLC dose groups) was 12.1 mg/d (17.7%) lower compared with the vehicle group. Compared with vehicle, urinary phosphate excretion was 28.1 mg/d (41.3%) lower in the combination OLC+tenapanor groups ( = 0.016). Bliss model of independence assessing the statistical significance between observed and predicted results indicated that combination OLC+tenapanor was synergistic ( = 0.009 for 0.75% OLC+tenapanor and = 0.010 for 1.5% OLC+tenapanor).
We demonstrated sizable reductions in urinary phosphate excretion in response to OLC monotherapy and the most pronounced reductions in urinary phosphate excretion when using OLC in combination with tenapanor.
碳酸氧化镧+替那帕诺联合治疗比单独使用任何一种药物都能更显著地降低尿磷排泄。我们证明了碳酸氧化镧单药治疗可使尿磷排泄呈剂量依赖性且大幅降低。
本研究评估了一种研究性磷结合剂碳酸氧化镧（OLC）和一种已获批的钠/氢交换体3抑制剂替那帕诺对高磷饮食大鼠尿磷排泄的联合作用，替那帕诺可减少细胞旁磷吸收。
64只雄性Sprague Dawley大鼠被随机分为八组：赋形剂组；仅替那帕诺（0.15mg/kg）组；仅OLC（0.75%、1.5%和3%）组；以及联合OLC（0.75%、1.5%和3%）+替那帕诺（0.15mg/kg）组。赋形剂和替那帕诺每天口服给药两次，而OLC被添加到饮食中。我们收集24小时尿液样本以测量尿磷排泄，作为肠道磷吸收效率的指标。主要分析比较了三个OLC剂量组的汇总结果。
在替那帕诺0.15mg/kg组中，第9至11天的平均尿磷排泄量比赋形剂组低8.5mg/d（12.5%）。在仅使用OLC的组中，平均尿磷排泄量（0.75%、1.5%和3% OLC剂量组汇总）比赋形剂组低12.1mg/d（17.7%）。与赋形剂组相比，联合OLC+替那帕诺组的尿磷排泄量低28.1mg/d（41.3%）（P = 0.016）。评估观察结果与预测结果之间统计学意义的布利斯独立性模型表明，联合OLC+替那帕诺具有协同作用（0.75% OLC+替那帕诺组P = 0.009，1.5% OLC+替那帕诺组P = 0.010）。
我们证明了碳酸氧化镧单药治疗可使尿磷排泄大幅降低，而碳酸氧化镧与替那帕诺联合使用时尿磷排泄降低最为显著。
