Effective Oral Iron Supplement for Pre-dialysis Patients

描述（由申请人提供）：贫血的发展是慢性肾衰竭的主要问题。在透析前期用重组人促红细胞生成素（rHuEpo）预防/早期治疗是很重要的。有效的铁是rHuEpo有效作用所必需的；经常需要补充铁元素；口服铁治疗是首选模式。这些患者口服铁的可用性差异很大；它的效力不能得到保证。我们建议开发一种无创方法来直接评估确定铁吸收的两个步骤：初始粘膜摄取（IMU），粘膜-浆膜转移（MST）。我们的方法是口服含有已知数量的稳定同位素标记的58FESO4、不可吸收标记物DyC13和视觉标记物亮蓝色的GelCap给禁食的患者，然后在实验室分析粪便中视觉标记的样品中58Fe- Excess/Dy的比率。将这一比例与已知的Dy摄入量归一化，得到IMU。对两周后采集的血液样本进行实验室分析，检测58fe过量，提供了全身潴留的数据，其与IMU的比率为MST。我们假设铁吸收（IMU和MST）与铁储存（如血清铁蛋白所示）之间的负相关是这些患者口服铁吸收变化很大的基础；铁的吸收可以通过长期摄入安全剂量的抗坏血酸和/或适当的rHuEpo治疗来增强。在第一阶段，我们将通过检验以下假设来确定该方法的可行性：透析前患者的非血红素铁（IMU和MST）的吸收与血清铁蛋白呈负相关，在20名透析前患者中，血清铁蛋白在临床实践中预期的范围内。在第二阶段，我们将重点研究如何通过合理给药抗坏血酸和rHuEpo来优化铁的吸收（IMU和MST）。

DESCRIPTION (provided by applicant): Development of anemia is a major problem in chronic renal failure. Its prevention/early treatment with recombinant human erythropoietin (rHuEpo) during pre-dialysis phase is important. Available iron is required for efficient action of rHuEpo; iron supplements are often needed; oral iron therapy is the preferred mode. Availability of oral iron varies widely in these patients; its efficacy cannot be ensured. We propose to develop a noninvasive method for direct assessment of the two steps that determine iron absorption: initial mucosal uptake (IMU), mucosal-serosal transfer (MST). Our approach is based on oral administration of a GelCap with known amounts of stable-isotope-labeled 58FESO4, the non-absorbable marker DyC13, and the visual marker brilliant blue to fasted patients, followed by laboratory analysis of the ratio 58Fe- Excess/Dy in the visually-marked sample of stool. Normalizing this ratio to the known intake of Dy yields IMU. Laboratory analysis of a blood sample taken two weeks later for 58Fe-Excess provides data for whole-body retention and the ratio of this to IMU is MST. We hypothesize that the inverse correlation between iron absorption (IMU and MST) and iron stores (as indicated by serum ferritin) is the basis for the widely variable absorption of oral iron in these patients; and that iron absorption can be enhanced by chronic ingestion of safe doses of ascorbic acid, and/or appropriate rHuEpo treatment. During Phase-I we will establish the feasibility of the approach by testing the following HYPOTHESIS: absorption of nonheme iron (IMU and MST) is inversely related to serumferritin in pre-dialysis patients, in 20 pre-dialysis patients with serum ferritin in the range expected in clinical practice. During Phase-II we will focus on how to optimize iron absorption (IMU and MST) by judicious administration of ascorbic acid and rHuEpo.