尿素的动力学行为不同于其他水溶性化合物：胍基化合物的情况。

Kinetic behavior of urea is different from that of other water-soluble compounds: the case of the guanidino compounds.

作者信息

Eloot Sunny, Torremans An, De Smet Rita, Marescau Bart, De Wachter Dirk, De Deyn Peter Paul, Lameire Norbert, Verdonck Pascal, Vanholder Raymond

机构信息

Institute Biomedical Technology, Hydraulics Laboratory, Ghent University, Belgium.

出版信息

Kidney Int. 2005 Apr;67(4):1566-75. doi: 10.1111/j.1523-1755.2005.00238.x.

DOI:10.1111/j.1523-1755.2005.00238.x

PMID:15780113

Abstract

BACKGROUND

Although patients with renal failure retain a large variety of solutes, urea is virtually the only currently applied marker for adequacy of dialysis. Only a limited number of other compounds have up until now been investigated regarding their intradialytic kinetics. Scant data suggest that large solutes show a kinetic behavior that is different from urea. The question investigated in this study was whether other small water-soluble solutes, such as some guanidino compounds, show a kinetic behavior comparable or dissimilar to that of urea.

METHODS

This study included 7 stable conventional hemodialysis patients without native kidney function undergoing low flux polysulphone dialysis (F8 and F10HPS). Blood samples were collected from the inlet and outlet bloodlines immediately before the dialysis session, after 5, 15, 30, 120 minutes, and immediately after discontinuation of the session. Plasma concentrations of urea, creatinine (CTN), creatine (CT), guanidinosuccinic acid (GSA), guanidinoacetic acid (GAA), guanidine (G), and methylguanidine (MG) were used to calculate corresponding dialyzer clearances. A two-pool kinetic model was fitted to the measured plasma concentration profiles, resulting in the calculation of the perfused volume (V(1)), the total distribution volume (V(tot)), and the intercompartmental clearance (K(12)); solute generation and overall ultrafiltration were determined independently.

RESULTS

No significant differences were observed between V(1) and K(12) for urea (6.4 +/- 3.3 L and 822 +/- 345 mL/min, respectively) and for the guanidino compounds. However, with respect to V(tot), GSA was distributed in a smaller volume (30.6 +/- 4.2 L) compared to urea (42.7 +/- 6.0L) (P < 0.001), while CTN, CT, GAA, G, and MG showed significantly higher volumes (54.0 +/- 5.9 L, 98.0 +/- 52.3 L, 123.8 +/- 66.9 L, 89.7 +/- 21.4 L, 102.6 +/- 33.9 L, respectively; P= 0.004, = 0.033, = 0.003, < 0.001, = 0.001, respectively). These differences resulted in divergent effective solute removal: 67% (urea), 58% (CTN), 42% (CT), 76% (GSA), 37% (GAA), 43% (G), and 42% (MG).

CONCLUSION

The kinetics of the guanidino compounds under study are different from that of urea; hence, urea kinetics are not representative for the removal of other uremic solutes, even if they are small and water-soluble like urea.

摘要

背景

尽管肾衰竭患者体内潴留多种溶质，但尿素实际上是目前唯一用于评估透析充分性的标志物。到目前为止，仅有少数其他化合物的透析中动力学情况得到研究。少量数据表明，大分子溶质呈现出与尿素不同的动力学行为。本研究探讨的问题是，其他一些水溶性小分子溶质，如某些胍类化合物，其动力学行为与尿素相比是相似还是不同。

方法

本研究纳入7例无自身肾功能的稳定的常规血液透析患者，采用低通量聚砜膜透析器（F8和F10HPS）进行透析。在透析开始前、透析5、15、30、120分钟时以及透析结束后即刻，从血液透析管路的入口和出口采集血样。检测血浆中尿素、肌酐（CTN）、肌酸（CT）、胍基琥珀酸（GSA）、胍基乙酸（GAA）、胍（G）和甲基胍（MG）的浓度，用于计算相应的透析器清除率。采用双池动力学模型拟合测得的血浆浓度曲线，计算灌注容积（V(1)）、总分布容积（V(tot)）和室间清除率（K(12)）；独立测定溶质生成量和总超滤量。

结果

尿素（分别为6.4±3.3 L和822±345 mL/min）和胍类化合物的V(1)和K(12)之间未观察到显著差异。然而，就V(tot)而言，与尿素（42.7±6.0L）相比，GSA分布容积较小（30.6±4.2 L）（P<0.001），而CTN、CT、GAA、G和MG的分布容积显著更大（分别为54.0±5.9 L、98.0±52.3 L、123.8±66.9 L、89.7±21.4 L、102.6±33.9 L；P分别为0.004、0.033、0.003、<0.001、0.001）。这些差异导致有效溶质清除率不同：尿素为67%，CTN为58%，CT为42%，GSA为76%，GAA为37%，G为43%，MG为42%。