Laboratory of Molecular Pharmacology, Faculty of Health Sciences, University of Brasília, Brasília, Brazil.
Department Kidney Transplantation, Clínica de Doenças Renais de Brasília, Brasília, Brazil.
Blood Purif. 2023;52(3):242-254. doi: 10.1159/000528983. Epub 2023 Jan 19.
A hallmark of chronic kidney disease is the retention of solutes that normally are eliminated by the kidneys. The current classification defines uremic toxins based on molecular weight and protein affinity. The retention of solutes is already detected in the early stages of the disease when patients are pauci-symptomatic or asymptomatic but the role of therapies to retard the loss of kidney function in patients with chronic kidney disease (e.g., modulators of the renin-angiotensin-aldosterone system, sodium-glucose cotransporter inhibitors) in reducing uremic toxins is poorly understood. Most of the research evaluating the impact of therapies to lower serum concentrations of those toxic compounds is carried out in patients with kidney failure already undergoing kidney replacement therapy. The removal of those molecules relies in physicochemical mass transfer phenomena, i.e., adsorption, diffusion, and convection. In the past 2 decades, the rise and broad adoption of blood purification strategies with enhanced convective properties, such as high-volume online hemodiafiltration and expanded hemodialysis, considerably amplified the ability to mechanically extract middle molecules (molecular weight >0.5 kDa) from the blood compartment. Nonetheless, the classification of uremic toxins has not evolved in parallel with dialysis advancements. Mounting evidence demonstrates the link between middle molecules with uremic symptoms, cardiovascular and mortality risks. An urgent need for updating the classification exists. Defining the causative relationship between specific solutes and specific clinical outcomes will promote the development of targeted therapies. In parallel, the inclusion of new pertinent dimensions to the classification like the influence of new dialysis membranes, sorbents, and intestinal chelators in the concentration of uremic toxins would improve the understanding of the pathogenesis of chronic kidney disease, setting the pace for future research in nephrology.
慢性肾脏病的一个特征是溶质的潴留，这些溶质通常通过肾脏被清除。目前的分类是基于分子量和蛋白质亲和力来定义尿毒症毒素的。当患者出现少症状或无症状时，疾病的早期阶段就已经检测到溶质的潴留，但慢性肾脏病患者减缓肾功能丧失的治疗（例如，肾素-血管紧张素-醛固酮系统调节剂、钠-葡萄糖共转运蛋白抑制剂）对尿毒症毒素的作用尚不清楚。大多数评估降低这些有毒化合物血清浓度的治疗方法的影响的研究都是在已经接受肾脏替代治疗的肾衰竭患者中进行的。这些分子的清除依赖于物理化学质量传递现象，即吸附、扩散和对流。在过去的 20 年中，具有增强对流特性的血液净化策略（如大容量在线血液透析滤过和扩展血液透析）的兴起和广泛采用，大大提高了从血液隔室中机械提取中分子（分子量>0.5 kDa）的能力。尽管如此，尿毒症毒素的分类并没有随着透析技术的进步而发展。越来越多的证据表明中分子与尿毒症症状、心血管和死亡风险之间存在关联。迫切需要对其进行分类更新。确定特定溶质与特定临床结局之间的因果关系将促进靶向治疗的发展。与此同时，将新的相关维度（如新的透析膜、吸附剂和肠道螯合剂对尿毒症毒素浓度的影响）纳入分类中，将有助于深入了解慢性肾脏病的发病机制，为肾脏病学的未来研究指明方向。
