Supplementary Material for: Effect of Niacin on FGF23 Concentration in Chronic Kidney Disease

<b><i>Background:</i></b> Elevated serum phosphorus and FGF23 are independent cardiovascular risk factors in patients with chronic kidney disease. In a randomized controlled trial of patients with dyslipidemia assigned to either extended release niacin (ERN) alone, ERN combined with the selective prostaglandin D₂ receptor subtype 1 inhibitor laropiprant (ERN-L) or placebo, niacin lowered serum phosphorus; however, it is not known if it lowers FGF23 concentrations. <b><i>Methods:</i></b> This is an ancillary study to a multicenter, randomized, double-blind, placebo-controlled trial among patients with dyslipidemia and an estimated glomerular filtration rate (eGFR) of 30-74 ml/min/1.73 m². Participants were randomized to ERN-L (n = 162), ERN (n = 97), or placebo (n = 68) in a 3:2:1 ratio for 24 weeks. The primary outcome was a change in serum FGF23 concentrations, and secondary outcomes were changes in other mineral metabolism parameters. <b><i>Results:</i></b> Both the ERN and ERN-L groups showed significant declines in serum phosphorus, calcium and calcium·phosphorus product at 24 weeks compared to placebo. A significant decline from baseline (10.9%, p &lt; 0.01) in the serum FGF23 concentration was observed in the ERN group compared to placebo, but not in the ERN-L group compared to placebo (p = 0.36 and 0.97 for ERN-L and placebo, respectively), despite equivalent declines in serum phosphorus. Similarly, the most marked declines in PTH occurred in the ERN-only group versus placebo; no change in PTH was observed in the ERN-L group. <b><i>Conclusions:</i></b> In this ancillary study of hyperlipidemic patients with an eGFR of 30-74 ml/min/1.73 m², ERN alone but not in combination with laropiprant lowered FGF23 and PTH concentrations. If confirmed, niacin may provide a novel strategy to decrease phosphorus, FGF23, and PTH concentrations in patients with chronic kidney disease.背景：血清磷升高与成纤维细胞生长因子23（fibroblast growth factor 23, FGF23）水平升高是慢性肾脏病（chronic kidney disease, CKD）患者独立的心血管危险因素。在一项针对血脂异常患者的随机对照试验中，受试者被分配至单独缓释烟酸（extended release niacin, ERN）组、缓释烟酸联合选择性前列腺素D₂受体1亚型抑制剂拉罗匹仑（laropiprant, ERN-L）组或安慰剂组，既往研究显示烟酸可降低血清磷水平，但目前尚不清楚其是否可降低FGF23浓度。方法：本研究为一项多中心、随机、双盲、安慰剂对照试验的亚组研究，纳入对象为血脂异常且估算肾小球滤过率（estimated glomerular filtration rate, eGFR）为30~74 ml/min/1.73m²的患者。受试者按3:2:1的比例随机分配至ERN-L组（n=162）、ERN组（n=97）或安慰剂组（n=68），干预时长为24周。本研究的主要结局指标为血清FGF23浓度的变化，次要结局指标为其他矿物质代谢参数的变化。结果：与安慰剂组相比，ERN组与ERN-L组在24周时的血清磷、钙及钙磷乘积均显著降低。尽管两组的血清磷下降幅度相当，但与安慰剂组相比，ERN组的血清FGF23浓度较基线下降10.9%，差异具有统计学意义（p<0.01）；而ERN-L组与安慰剂组相比无显著差异，两组比较的p值分别为0.36与0.97。类似地，与安慰剂组相比，仅使用ERN的组甲状旁腺激素（parathyroid hormone, PTH）下降最为显著；而ERN-L组的PTH水平未观察到明显变化。结论：在本项针对估算肾小球滤过率为30~74 ml/min/1.73m²的血脂异常患者的亚研究中，单独使用缓释烟酸（ERN）可降低FGF23与PTH浓度，而联合拉罗匹仑则无此效果。若该结论得以验证，烟酸或可为慢性肾脏病患者降低血清磷、FGF23及PTH浓度提供全新的干预策略。