终末期肾病病人静脉补铁引起脑铁过载的机制及定量MRI研究

The serious anemia often occurs in patients with end-stage renal disease (ESRD). Combination of erythropoietin and intravenous iron supplimentation can improve the anemia, but also result in iron overload. Now there are no definite criteria for the amount of intravenous iron injection. The iron overload can result in cerebral iron deposition , damage of cerebral small vascular, leadto cerebral microbleeds (CMBs) ,change whole cerebral blood flow and cerebral oxygen metabolism. Our previous study found the increased cerebral iron deposition occurred in patients with haemodialysis and correlated with cerebral atrophy and cognitive dysfunction. This research collected 60 ESRD patients without haemodialysis, 60 ESRD patients with haemodialysis and 60 healthy controls. During the therapy of intravenous iron injection for the correction of anemia, quantitative susceptibility mapping (QSM) was used to explore the whole brain iron deposition and CMBs caused by iron overload. The cerebral blood flow and oxygen metabolic sequence constructed by arterial spin labeling (ASL) time sequence was used to quantify the changes of the network of cerebral blood flow and oxygen metabolism. The study will explore the mechanism of iron overload—cerebral iron deposition—CMBs—cerebral blood flow and oxygen metabolism. The imaging biomarkers was investigated for monitoring the iron storage of whole body in patients with ESRD, providing a new theoretical basis of anemia corrected by clinical intravenous iron injection.

终末期肾病病人伴有明显的贫血，联合静脉给铁和促红素治疗改善了病人的贫血，但存在铁过载。目前没有明确的静脉给铁剂量的标准。铁过载引起广泛的脑铁沉积及损伤脑小血管，导致脑微出血、全脑血流及氧代谢的改变。课题组既往发表的文章发现血液透析病人脑内一些结构铁沉积增加，而且增加的铁沉积与脑萎缩及痴呆相关。本课题收集终末期肾病未透析及透析病人各60例、正常对照60例，在纠正病人缺铁性贫血静脉给铁治疗中，采用定量磁敏感加权成像研究铁过载引起的全球性脑组织铁沉积及微出血，利用ASL时间序列同时构成的血流量和氧代谢序列，量化终末期肾病病人铁过载引起的脑血流及氧代谢网络改变，揭示铁过载─脑铁沉积─脑微出血─脑血流及氧代谢改变的机制。深入探索静脉给铁纠正终末期肾病病人贫血脑铁沉积及微出血的分布、脑血流及氧代谢网络的改变，以期发现监测终末期肾病病人全身铁存储量的影像诊断指标，为临床治疗贫血静脉补铁提供新的理论依据。

1.研究立项背景： .血液透析是终末期肾病（End-stage renal disease，ESRD）病人较常见的维持性治疗方法，但可导致贫血。贫血的治疗采用静脉补铁与促红素联合进行，进而会导致铁过载。虽然铁过载的诊断标准已明确，但铁过载在脑组的沉积情况尚未见相关报道。同时铁过载也是脑血管病的危险因素，可导致脑微出血、脑血流改变，而脑血流的改变会伴随脑氧代谢的变化。目前脑铁过载导致脑小血管损伤后脑微出血、脑血流及氧代谢改变的机制还需要进一步研究。2.研究目的：.寻找指导临床静脉给铁治疗贫血引起铁过载的敏感性监测指标； 探讨终末期肾病及血液透析病人脑铁沉积对于脑微出血、脑血流及氧代谢变化的影响及机制。.3.研究内容及研究方法：.内容：（1）探讨铁过载导致脑组织内铁沉积及微出血发生的敏感部位，作为指导临床静脉给铁治疗贫血引起铁过载的敏感性监测指标；（2）探讨终末期肾病及血液透析病人脑铁沉积对于全脑血流及氧代谢变化的影响及机制。.方法： 拟收集ESRD未行及行血液透析病人、正常对照组，进行磁敏感加权成像、动脉自旋标记成像及流行病学、临床血生化指标的采集。观察全脑铁含量及局部铁含量分布、微出血数量、分布及铁含量、脑血流量与氧代谢情况；分别将上述影像指标与流行病学、临床血生化指标进行相关分析，获得铁过载的敏感性指标。.4.重要结果及关键数据：.纵向随访发现血透病人脑铁过载，且铁过载与钙磷代谢异常、肌酐等危险因素有关。微出血是血透患者常见并发症，主要位于基底节区与脑干，年龄与透析前后收缩压是微出血的危险因素。血透病人大脑深部及局部静脉血氧饱和度减低。血透病人核团脑血流量增加，且增加的脑血流量与核团的铁含量存在相关性。正常人脑铁含量与静脉血氧饱和度的存在相关性。.5.科学意义：.探索静脉给铁纠正终末期肾病病人贫血脑铁沉积及微出血的分布、脑血流及氧代谢网络的改变，以期发现监测透析病人铁存储的影像诊断指标，为临床静脉补铁治疗贫血提供新的理论依据。