van de Kerkhof Jos, Schalkwijk Casper G, Konings Constantijn J, Cheriex Emile C, van der Sande Frank M, Scheffer Peter G, ter Wee Piet M, Leunissen Karel M, Kooman Jeroen P
MD Department of Internal Medicine, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
Nephrol Dial Transplant. 2004 Apr;19(4):910-6. doi: 10.1093/ndt/gfh004.
Advanced glycation end products (AGEs) may contribute to peritoneal and cardiovascular damage in peritoneal dialysis (PD) patients, possibly in part by over-expression of vascular cell adhesion molecule-1 (VCAM-1). It has been suggested that peritoneal glucose load, oxidative stress, as well as the uraemic state itself may lead to an increased formation of AGEs. Aims of the present study were first to investigate the relation between residual glomerular filtration rate (rGFR), malondialdehyde (MDA) as a marker of lipid peroxidation, and peritoneal glucose prescription and absorption with serum levels of VCAM-1 and with the well characterized AGEs N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL), as well as with CML and CEL in peritoneal effluent.
CML and CEL were measured by tandem mass spectroscopy, MDA by HPLC, and VCAM-1 by ELISA in 37 stable PD patients (age 54 +/- 12 years; time on PD 25 +/- 18 months). CML and CEL were also measured after a 4-month interval.
rGFR was independently related to CML both in serum (r = -0.66; P<0.001) and effluent (r = -0.62; P<0.001), whereas peritoneal glucose prescription and absorption were, respectively, related to CML in serum and effluent (r = 0.49; P<0.001 and r = 0.44; P<0.01). Relationships were comparable when assessed after the follow-up period. Peritoneal glucose absorption (r = 0.37; P<0.05), but not rGFR, was related to CEL in serum. The relation between peritoneal glucose prescription and CML in effluent lost significance when rGFR was added to the multi-regression model. Both rGFR (r = -0.40; P<0.05) and peritoneal glucose absorption (r = 0.37; P<0.05) were associated with VCAM-1 expression, which was itself weakly related only to CML in effluent (r = 0.38; P<0.05). MDA was not related to any parameter.
Peritoneal glucose prescription and absorption, as well as rGFR are related to serum and effluent levels of CML and to VCAM-1 expression in serum, whereas peritoneal glucose absorption was related to serum levels of CEL. Still, the effect of rGFR, which does not appear to be mediated through lipid peroxidation pathways, on effluent levels of CML appears to outweigh the effect of the PD treatment. Even small differences in residual renal function in patients already on dialysis therapy are related to large variations of CML in serum and the peritoneal cavity.
晚期糖基化终末产物（AGEs）可能在腹膜透析（PD）患者中导致腹膜和心血管损害，可能部分是通过血管细胞黏附分子-1（VCAM-1）的过度表达。有人提出，腹膜葡萄糖负荷、氧化应激以及尿毒症状态本身可能导致AGEs形成增加。本研究的目的首先是探讨残余肾小球滤过率（rGFR）、作为脂质过氧化标志物的丙二醛（MDA）、腹膜葡萄糖处方和吸收与血清VCAM-1水平、以及特征明确的AGEs N-ε-（羧甲基）赖氨酸（CML）和N-ε-（羧乙基）赖氨酸（CEL），以及腹膜透析液中CML和CEL之间的关系。
采用串联质谱法测定37例稳定的PD患者（年龄54±12岁；PD时间25±18个月）的CML和CEL，采用高效液相色谱法测定MDA，采用酶联免疫吸附测定法测定VCAM-1。4个月后再次测定CML和CEL。
rGFR与血清（r = -0.66；P<0.001）和透析液（r = -0.62；P<0.001）中的CML均独立相关，而腹膜葡萄糖处方和吸收分别与血清和透析液中的CML相关（r = 0.49；P<0.001和r = 0.44；P<0.01）。随访期后评估时，关系具有可比性。腹膜葡萄糖吸收（r = 0.37；P<0.05）与血清中的CEL相关，但rGFR与血清中的CEL无关。当将rGFR加入多元回归模型时，腹膜葡萄糖处方与透析液中CML的关系失去显著性。rGFR（r = -0.40；P<0.05）和腹膜葡萄糖吸收（r = 0.37；P<0.05）均与VCAM-1表达相关，而VCAM-1本身仅与透析液中的CML弱相关（r = 0.38；P<0.05）。MDA与任何参数均无关。
腹膜葡萄糖处方和吸收以及rGFR与血清和透析液中CML水平以及血清中VCAM-1表达相关，而腹膜葡萄糖吸收与血清中CEL水平相关。尽管如此，rGFR对透析液中CML水平的影响似乎超过了PD治疗的影响，且其影响似乎并非通过脂质过氧化途径介导。即使是已经接受透析治疗的患者，残余肾功能的微小差异也与血清和腹膜腔中CML的大幅变化相关。
