Binding of hippurate in normal plasma and in uremic plasma pre- and postdialysis.
Binding of hippurate in normal plasma and in uremic plasma pre- and postdialysis.
复制标题
正常血浆和透析前后尿毒症血浆中马尿酸的结合。
作者：
Peter C. Farrell;Frank A. Gotch;John H. Peters;Bernard J. Berridge, jr.;Maryann Lam
14 C-马尿酸盐的蛋白结合已被测量的常规超滤技术在血浆中的正常受试者和尿毒症受试者透析前和透析后。此外，在体外测定了等渗盐水和血浆中14 C-马尿酸盐的清除率，以评估透析期间马尿酸盐清除的结合限制。正常受试者的马尿酸结合水平为68+/-1.8%（n = 5），显著高于同一尿毒症受试者透析后（48.3+/-15.4%; n = 7）或透析前（36.6+/-11.7%; n = 7）水平。然而，尿毒症患者血浆马尿酸盐的实际水平（24.7 ± 11.2 mg/dl，n = 7）显著高于正常受试者（0.5 mg%）。尿毒症患者透析前和透析后样本之间的马尿酸盐结合差异与零差异显著（p <0.01，t = 5.36），表明透析期间竞争性位点结合物质耗尽。在标准条件下，在毛细管透析器（CDAK-4）中马尿酸的生理盐水清除率（99.1 +/-0.5 ml/min; n = 6）与其分子量溶质的预期清除率一致。柠檬酸盐血浆中马尿酸清除率（结合率确定为50+/-3%）为65+/-0.7 ml/min（n = 6），与该结合水平的理论预测清除率60 ml/min非常一致。血清中马尿酸盐及其衍生物水平高，可能会抑制各种器官的有效功能。除了马尿酸盐及其前体的正常饮食摄入外，透析患者还接受了苯甲醇形式的马尿酸盐前体的进一步负担，苯甲醇是肝素溶液中的常见防腐剂。透析患者中马尿酸盐的大量身体负荷，加上由于结合导致的透析清除受损，表明有必要对该化合物的潜在毒性进行全面研究。
The protein binding of 14C-hippurate has been measured by conventional ultrafiltration techniques in the plasma of normal subjects and in uremic subjects pre- and postdialysis. In addition, the clearance of 14C-hippurate was determined in vitro in both isotonic saline and plasma to assess binding limitations on hippurate removal during dialysis. Binding levels of hippurate in normal subjects of 68+/-1.8% (n = 5) were significantly higher than either postdialysis (48.3+/-15.4%; n = 7) or predialysis (36.6+/-11.7%; n = 7) levels in the same uremic subjects. Actual levels of plasma hippurate were, however, considerably greater in uremics (24.7+/-11.2 mg/dl' n = 7) than in normal subjects (congruent to 0.5 mg%). The difference in hippurate binding between pre- and postdialysis samples in uremics was significantly different from zero (p less than 0.01, t = 5.36), indicating depletion of competitive site-binding species during dialysis. The saline clearance of hippuric acid (99.1 +/-0.5 ml/min; n = 6) under standard conditions in a capillary dialyzer (CDAK-4) was consistent with the expected clearance of a solute of its molecular weight. Hippurate clearance in citrated plasma, where binding was determined as 50+/-3%, was 65+/-0.7 ml/min (n = 6), in good agreement with a theoretically predicted clearance of 60 ml/min for this level of binding. High serum levels of hippurate and its derivatives, may depress effective function of various organs. In addition to the normal dietary intake of hippurate and its precursors, patients on dialysis receive a further burden of hippurate precursor in the form of benzyl alcohol, the common preservative in heparin solutions. The large body burdens of hippurate in dialysis patients, coupled with its impaired removal on dialysis due to binding, point to the necessity for a through investigation of the potential toxicity of this compound.