Umanath Kausik, Jalal Diana I, Greco Barbara A, Umeukeje Ebele M, Reisin Efrain, Manley John, Zeig Steven, Negoi Dana G, Hiremath Anand N, Blumenthal Samuel S, Sika Mohammed, Niecestro Robert, Koury Mark J, Ma Khe-Ni, Greene Tom, Lewis Julia B, Dwyer Jamie P
Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, Michigan;
Renal Diseases and Hypertension, University of Colorado, Denver, Colorado;
J Am Soc Nephrol. 2015 Oct;26(10):2578-87. doi: 10.1681/ASN.2014080842. Epub 2015 Mar 3.
Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0-28.9] versus 26.8 [13.4-47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023-9695] versus 6954 [2664-12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders.
柠檬酸铁（FC）是一种磷结合剂，已显示出疗效，并对铁储存、静脉注射（iv）铁的使用以及促红细胞生成素（ESA）有额外作用。我们对一项3期国际随机临床试验的活性对照期内各时间点的铁/血液学参数变化以及静脉注射铁/ESA的使用情况进行了详细分析。共有441名受试者被随机分组（292名接受FC，149名接受碳酸司维拉姆和/或醋酸钙[活性对照（AC）]），并随访52周。到第12周时，与接受AC的受试者相比，接受FC的受试者的铁蛋白和转铁蛋白饱和度（TSAT）水平有所升高（铁蛋白变化，114.1±29.35 ng/ml；P<0.001；TSAT变化，8.62%±1.57%；P<0.001）。此时TSAT的变化趋于平稳，而铁蛋白的变化在第24周前持续增加，并在之后保持相对稳定。在52周内，与接受AC的受试者相比，接受FC的受试者所需的静脉注射铁更少（中位[四分位间距]剂量=12.9[1.0 - 28.9]对26.8[13.4 - 47.6]mg/周；P<0.001），并且接受FC的受试者中不需要静脉注射铁的比例更高（P<0.001）。FC在52周内的累积ESA低于AC（中位[四分位间距]剂量=5303[2023 - 9695]对6954[2664 - 12,375]单位/周；P = 0.04）。总体而言，90.3%接受FC的受试者和89.3%接受AC的受试者经历了不良事件。总之，使用FC作为磷结合剂进行治疗会在12周后使铁参数升高，并在52周内降低静脉注射铁和ESA的使用量，同时维持血红蛋白水平，其安全性与现有结合剂相似。
