Arnadottir M, Hultberg B, Wahlberg J, Fellström B, Dimény E
Department of Medicine, National University Hospital, Reykjavik, Iceland.
Kidney Int. 1998 Oct;54(4):1380-4. doi: 10.1046/j.1523-1755.1998.00112.x.
Hyperhomocysteinemia is by now an established risk factor for the development of atherosclerosis. Total homocysteine concentration (tHcy) correlates inversely with glomerular filtration rate, and it is roughly three times as high in hemodialysis patients as in healthy individuals. Therefore, tHcy would be expected to fall markedly after successful renal transplantation. The aim of the present study was to assess the changes in tHcy associated with renal transplantation.
tHcy was analyzed in samples collected before renal transplantation and at six months after transplantation in 55 stable patients, all of whom were treated with cyclosporine (CS). tHcy was also analyzed in samples from 55 controls characterized by markers of renal function that matched those of the post-transplant state.
At six months after transplantation, tHcy was significantly decreased as compared with pretransplant tHcy (27.7 +/- 14.8 vs. 36.9 +/- 21.3 micromol/liter, P < 0.001). Post-transplant tHcy was markedly higher than the tHcy of the control group (27.7 +/- 14.8 vs. 16.0 +/- 5.3 micromol/liter, P < 0.0001). The post-transplant change in tHcy ranged widely, the average change being a reduction of 14%. Sixteen patients (29%) actually manifested an increase in post-transplant tHcy. The post-transplant changes in tHcy correlated inversely with pretransplant tHcy (r = -0.66, P < 0.0001) and directly with the changes in serum albumin concentrations (r = 0.35, P < 0.05) and CS trough concentrations (r = 0.29, P < 0.05). A multivariate analysis, including the post-transplant changes in serum concentrations of folate and albumin as well as creatinine clearances explained 21% of the change in tHcy (P < 0.05). After inclusion of the CS concentration, an independent predictor, the model accounted for 28% of the post-transplant change in tHcy (P < 0.01).
The post-transplant reduction in tHcy was far smaller than expected with respect to renal function, and the post-transplant changes in the major biochemical determinants of tHcy contributed relatively little to explain the change in tHcy. Thus, the results suggest the post-transplant introduction of one or more factors that induce an increase in tHcy. Treatment with CS appears to be such a factor.
高同型半胱氨酸血症目前是动脉粥样硬化发生的一个既定危险因素。总同型半胱氨酸浓度(tHcy)与肾小球滤过率呈负相关,并且在血液透析患者中其水平大约是健康个体的三倍。因此,成功肾移植后预计tHcy会显著下降。本研究的目的是评估与肾移植相关的tHcy变化。
对55例稳定患者肾移植前及移植后6个月采集的样本进行tHcy分析,所有患者均接受环孢素(CS)治疗。还对55例对照样本进行了tHcy分析,这些对照样本的肾功能指标与移植后状态相匹配。
移植后6个月时,与移植前tHcy相比,tHcy显著降低(27.7±14.8对36.9±21.3微摩尔/升,P<0.001)。移植后tHcy明显高于对照组tHcy(27.7±14.8对16.0±5.3微摩尔/升,P<0.0001)。移植后tHcy的变化范围很广,平均变化为降低14%。16例患者(29%)移植后tHcy实际出现升高。移植后tHcy的变化与移植前tHcy呈负相关(r = -0.66,P<0.0001),与血清白蛋白浓度变化呈正相关(r = 0.35,P<0.05)以及与CS谷浓度呈正相关(r = 0.29,P<0.05)。多因素分析,包括移植后血清叶酸和白蛋白浓度变化以及肌酐清除率,解释了tHcy变化的21%(P<0.05)。纳入CS浓度这一独立预测因素后,该模型解释了移植后tHcy变化的28%(P<0.01)。
就肾功能而言,移植后tHcy的降低远低于预期,并且tHcy主要生化决定因素的移植后变化对解释tHcy变化的贡献相对较小。因此,结果提示移植后引入了一种或多种导致tHcy升高的因素。CS治疗似乎就是这样一个因素。