MR biosignatures of uremia-induced tissue alterations in patients with chronic kidney disease and hemodialysis patients

慢性肾脏疾病(CKD)是全球范围内的医疗负担，其患病率也在不断增加。慢性肾脏病最终导致终末期肾脏疾病，需要肾脏替代治疗，如血液透析或肾移植。CKD患者面临着非常高的心血管发病率和死亡率，通常是由严重的电解质紊乱引起的。目前，确定肾脏疾病严重程度的诊断方法仅限于对体液(主要是血液和尿液样本)进行化学分析，以及评估患者的体重、浮肿和血压。因此，组织水平的慢性改变，如电解质平衡、尿毒症毒素积聚、组织pH变化和局部水肿，均未得到临床评估。磁共振生物签名可能通过揭示肾功能不全引起的组织特异性磁共振“指纹”来弥合这一差距。在我们的临床研究中，我们打算测量CKD患者的肌肉和脑组织，并将这些数据与年龄和性别匹配的健康对照组进行比较。我们打算检测常见主诉的病理生理学，如CKD患者经常出现的肌肉无力或认知障碍。此外，我们将在常规透析程序前后对接受维持性血液透析治疗的患者进行测量。MR生物特征的预期短期变化可能解释在透析治疗期间出现的严重肌肉痉挛或头晕/恶心等症状。对于这种方法，将与A1-A3项目密切合作开发几种MRI技术的组合，包括：23Na和39K MRI、化学交换饱和转移(CEST)、定量磁化率测绘(QSM)和扩散加权MRI。我们计划确定由于局部水肿、脂肪/液体含量的变化、电解质分布的变化以及两个组织中蛋白质/糖胺聚糖(GAG)含量的不同或pH值的变化而导致的显微结构差异。这些信息将在S项目中进行分析，也是通过人工智能的手段。我们期望在肾脏患者的组织特异性MR生物特征中发现不同于尿液或血液分析的变化。在未来，这一知识可能有助于临床医生确定启动肾脏替代治疗的最佳时间，并可能通过优化透析治疗方案来减少HD相关症状。

Chronic kidney disease (CKD) is a global health care burden with an increasing prevalence. CKD finally results in end-stage renal disease which requires renal replacement therapy such as hemodialysis or kidney transplantation. Patients with CKD face a very high risk of cardiovascular morbidity and mortality, often induced by severe electrolyte disturbance. Currently, diagnostic approaches to determine kidney disease severity are restricted to chemical analysis of body fluids (mainly blood and urine samples) together with the assessment of patient’s body weight, edema and blood pressure. Chronic alterations on the tissue level, e.g. electrolyte homeostasis, accumulation of uremic toxins, changes in tissue pH, and local edema therefore escape the clinical evaluation. MR-biosignatures might bridge this gap by revealing tissue specific MR “finger prints” caused by renal insufficiency. In our clinical study we intend to measure muscle as well as brain tissue in CKD patients and compare this data with age- and gender matched healthy controls. We intend to detect the pathophysiology of common complains, like muscle weakness or cognitive impairment frequently occurring in CKD patients. Additionally, we will measure patients on maintenance hemodialysis treatment before and after their regular dialysis procedure. The expected short-term changes in MR-biosignatures might explain symptoms such as severe muscle cramps or dizziness/nausea which occur during dialysis treatment. For this approach a combination of several MRI techniques will be developed in close cooperation with projects A1-A3, including: 23Na and 39K MRI, Chemical Exchange Saturation Transfer (CEST), Quantitative Susceptibility Mapping (QSM), and diffusion-weighted MRI. We plan to determine microstructural differences due to local edema, changes in fat-/ fluid content, alterations in electrolyte distribution as well as differing protein/ glycosaminoglycan (GAG) content or shifts in pH values in both tissues. This information will be analyzed in project S, also by means of artificial intelligence. We expect to find alterations in tissue specific MR-biosignatures of renal patients that differ from urine or blood analysis. In future this knowledge might help clinicians to determine the optimal time for initiating renal replacement therapy and might reduce HD associated symptoms by optimizing dialysis treatment regime.