Yalamarti Tanuja, Sirich Tammy L, Hai Xin, Suba Josef K, Keo Lindsey S, Chan Kristy H C, Meyer Timothy W
Departments of Medicine, Stanford University and VA Palo Alto HCS, Palo Alto, California.
Department of Pharmacy, Harbin Medical University, Harbin, China.
Kidney360. 2025 May 1;6(5):814-823. doi: 10.34067/KID.0000000712. Epub 2025 Jan 27.
Hemodialysis can relieve uremic symptoms only by lowering the plasma levels of causative solutes below what they were at dialysis initiation. This can happen only when the ratio of a solute's dialytic clearance to the clearance of the failing kidney is very high.
If GFR falls far enough, uremic symptoms, such as anorexia and nausea, prompt the initiation of dialysis. Thrice-weekly hemodialysis can prevent recurrence of these symptoms even when patients become anuric. To accomplish this, it must maintain the plasma levels of the uremic solutes, which cause these symptoms to be lower than they were when dialysis was initiated. This study examined kinetic properties that solutes must possess for hemodialysis to accomplish this. We also sought to identify uremic solutes that possess these properties.
Mathematical modeling analyzed how a solute's kinetic properties would determine the relation of its level in an anuric patient on dialysis to its level when uremic symptoms prompt dialysis initiation. The previously unstudied solute methylurea (MU) was assayed by liquid chromatography tandem mass spectrometry in 13 participants on hemodialysis, nine participants with advanced CKD, and ten participants without kidney disease.
Mathematical modeling showed that conventional dialysis can effectively control the plasma levels better than the failing native kidneys only of solutes, which have a high dialytic clearance relative to their native kidney clearance and a large volume of distribution. Liquid chromatography tandem mass spectrometry measurements showed that MU has these properties. The dialytic clearance of MU was 255±32 ml/min, and its volume of distribution was 1.09±0.25 times the body water volume in patients on hemodialysis. The MU clearance was lower than the GFR in patients without kidney disease (fractional clearance 0.44±0.19) and patients with advanced CKD (fractional clearance 0.53±0.10). A literature review revealed that urea was the only solute previously known to possess these properties.
A further search for solutes whose properties include a high dialytic clearance, a relatively low native kidney clearance, and a high volume of distribution could help identify solutes that contribute to uremic symptoms.
血液透析仅通过将致病溶质的血浆水平降至低于透析开始时的水平，才能缓解尿毒症症状。只有当溶质的透析清除率与衰竭肾脏的清除率之比非常高时，才会发生这种情况。
如果肾小球滤过率（GFR）下降到足够程度，尿毒症症状，如厌食和恶心，会促使开始透析。即使患者无尿，每周三次的血液透析也可预防这些症状的复发。要做到这一点，它必须使导致这些症状的尿毒症溶质的血浆水平低于透析开始时的水平。本研究检查了溶质为使血液透析达到此目的必须具备的动力学特性。我们还试图鉴定具有这些特性的尿毒症溶质。
数学建模分析了溶质的动力学特性如何决定无尿透析患者体内其水平与其因尿毒症症状促使透析开始时的水平之间的关系。通过液相色谱串联质谱法对13例血液透析参与者、9例晚期慢性肾脏病（CKD）参与者和10例无肾脏疾病参与者的此前未研究的溶质甲基脲（MU）进行了测定。
数学建模表明，传统透析仅能比衰竭的天然肾脏更有效地控制具有相对于其天然肾脏清除率较高的透析清除率和较大分布容积的溶质的血浆水平。液相色谱串联质谱法测量显示MU具有这些特性。血液透析患者中MU的透析清除率为255±32 ml/min，其分布容积为身体水量的1.09±0.25倍。无肾脏疾病患者（清除率分数0.44±0.19）和晚期CKD患者（清除率分数0.53±0.10）的MU清除率低于GFR。文献综述显示尿素是此前已知的唯一具有这些特性的溶质。
进一步寻找特性包括高透析清除率、相对较低的天然肾脏清除率和高分布容积的溶质，可能有助于识别导致尿毒症症状的溶质。
