Camacho Orlando, Rosales Maria Carmela, Shafi Tariq, Fullman Jonathan, Plummer Natalie S, Meyer Timothy W, Sirich Tammy L
The Department of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, CA, USA.
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Nephrol Dial Transplant. 2016 Aug;31(8):1335-41. doi: 10.1093/ndt/gfw100. Epub 2016 May 17.
The protein-bound solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) accumulate to high plasma levels in renal failure and have been associated with adverse events. The clearance of these bound solutes can be altered independently of the urea clearance by changing the dialysate flow and dialyzer size. This study tested whether a sustained difference in clearance would change the plasma levels of PCS and IS.
Fourteen patients on thrice-weekly nocturnal hemodialysis completed a crossover study of two periods designed to achieve widely different bound solute clearances. We compared the changes in pre-dialysis plasma PCS and IS levels from baseline over the course of the two periods.
The high-clearance period provided much higher PCS and IS clearances than the low-clearance period (PCS: 23 ± 4 mL/min versus 12 ± 3 mL/min, P < 0.001; IS: 30 ± 5 mL/min versus 17 ± 4 mL/min, P < 0.001). Despite the large difference in clearance, the high-clearance period did not have a different effect on PCS levels than the low-clearance period [from baseline, high: +11% (-5, +37) versus low: -8% (-18, +32), (median, 25th, 75th percentile), P = 0.50]. In contrast, the high-clearance period significantly lowered IS levels compared with the low-clearance period [from baseline, high: -4% (-17, +1) versus low: +22% (+14, +31), P < 0.001). The amount of PCS removed in the dialysate was significantly greater at the end of the high-clearance period [269 (206, 312) versus 199 (111, 232) mg per treatment, P < 0.001], while the amount of IS removed was not different [140 (87, 196) versus 116 (89, 170) mg per treatment, P = 0.15].
These findings suggest that an increase in PCS generation prevents plasma levels from falling when the dialytic clearance is increased. Suppression of solute generation may be required to reduce plasma PCS levels in dialysis patients.
蛋白结合溶质对甲酚硫酸盐（PCS）和硫酸吲哚酚（IS）在肾衰竭患者体内血浆水平升高，并与不良事件相关。通过改变透析液流量和透析器尺寸，这些结合溶质的清除率可独立于尿素清除率而改变。本研究旨在测试清除率的持续差异是否会改变PCS和IS的血浆水平。
14例每周进行3次夜间血液透析的患者完成了一项交叉研究，该研究分为两个阶段，旨在实现截然不同的结合溶质清除率。我们比较了两个阶段中透析前血浆PCS和IS水平相对于基线的变化。
高清除率阶段的PCS和IS清除率远高于低清除率阶段（PCS：23±4 mL/分钟对12±3 mL/分钟，P<0.001；IS：30±5 mL/分钟对17±4 mL/分钟，P<0.001）。尽管清除率差异很大，但高清除率阶段对PCS水平的影响与低清除率阶段并无不同[相对于基线，高清除率阶段：+11%（-5，+37）对低清除率阶段：-8%（-18，+32），（中位数，第25百分位数，第75百分位数），P = 0.50]。相比之下，与低清除率阶段相比，高清除率阶段显著降低了IS水平[相对于基线，高清除率阶段：-4%（-17，+1）对低清除率阶段：+22%（+14，+31），P<0.001]。在高清除率阶段结束时，透析液中清除的PCS量显著增加[每次治疗269（206，312）毫克对199（111，232）毫克，P<0.001]，而清除的IS量没有差异[每次治疗140（87，196）毫克对116（89，170）毫克，P = 0.15]。
这些发现表明，当透析清除率增加时，PCS生成增加会阻止血浆水平下降。可能需要抑制溶质生成以降低透析患者的血浆PCS水平。
