Hörl W H
Wien Klin Wochenschr. 1998 Aug 21;110(15):511-20.
A variety of signs and symptoms constituting the uraemic syndrome may be related to the retention and accumulation of uraemic toxins. Several identified (and yet unidentified) uraemic toxins of low molecular weight are removed at least in part by dialysis therapy resulting in marked improvement of multiple organ dysfunctions and clinical symptoms. However, many abnormalities persist due to the high protein binding of several uraemic toxins or their high molecular weight associated with inadequate dialysis clearance. Moreover, carbamoylation of amino acids and proteins in uraemia as well as metabolic acidosis contribute to the functional and metabolic abnormalities of the uraemic state. Uraemia interferes with the function of polymor-phonuclear leukocytes by deranging their cellular biochemistry and biology. P-cresol and several newly identified granulocyte inhibitory proteins are responsible for reduced chemotaxis, oxidative activity, intracellular killing of bacteria, and glucose consumption by polymorphonuclear leukocytes. Hyperhomocysteinaemia is an independent risk factor for vascular disease in end-stage renal disease patients. Uraemic toxins interfere with calcitriol synthesis and concentration or activity of the calcitriol receptor. Advanced glycolysation end-products (AGEs) accumulate as a result of impaired renal excretion. AGE peptides may represent a modern-day version of "middle molecule" toxicity or uraemia. Of potential clinical importance are pentosidine-, imidazolone- and carboxymethyllysine-modifications of beta 2-microglobulin with respect to the development of uraemia associated amyloidosis. Several uraemic toxins also affect nitric oxide pathway. Particularly, dimethyl-L-arginine (ADMA) is a potent inhibitor of nitric oxide synthesis. Parathyroid hormone satisfies the strict criteria of an uraemic toxin. Many uraemic symptoms can be attributed to the excess of parathyroid hormone in patients with chronic renal failure. Finally, recent investigations indicate, that one or more dialyzable uraemic toxin(s) suppress(es) appetite and may contribute to malnutrition in uraemia.
构成尿毒症综合征的各种体征和症状可能与尿毒症毒素的潴留和蓄积有关。几种已确定（以及尚未确定）的低分子量尿毒症毒素至少部分可通过透析治疗清除，从而使多器官功能障碍和临床症状得到显著改善。然而，由于几种尿毒症毒素的高蛋白结合性或其高分子量导致透析清除不充分，许多异常情况仍然存在。此外，尿毒症时氨基酸和蛋白质的氨基甲酰化以及代谢性酸中毒也导致了尿毒症状态下的功能和代谢异常。尿毒症通过扰乱多形核白细胞的细胞生物化学和生物学特性来干扰其功能。对甲酚和几种新发现的粒细胞抑制蛋白导致多形核白细胞的趋化性降低、氧化活性降低、细胞内细菌杀伤能力降低以及葡萄糖消耗减少。高同型半胱氨酸血症是终末期肾病患者血管疾病的独立危险因素。尿毒症毒素干扰骨化三醇的合成以及骨化三醇受体的浓度或活性。由于肾脏排泄受损，晚期糖基化终产物（AGEs）会蓄积。AGE肽可能代表了“中分子”毒性或尿毒症的现代形式。就尿毒症相关淀粉样变性的发生而言，β2微球蛋白的戊糖苷、咪唑啉酮和羧甲基赖氨酸修饰具有潜在的临床重要性。几种尿毒症毒素也影响一氧化氮途径。特别是，二甲基-L-精氨酸（ADMA）是一氧化氮合成的强效抑制剂。甲状旁腺激素符合尿毒症毒素的严格标准。许多尿毒症症状可归因于慢性肾衰竭患者甲状旁腺激素过多。最后，最近的研究表明，一种或多种可透析的尿毒症毒素会抑制食欲，并可能导致尿毒症患者营养不良。
