Oxidized LDL: As a risk factor for cardiovascular disease in renal transplantation

ABSTRACT Objectives: The mortality rate of chronic kidney disease (CKD) patients that have undergone renal replacement therapy is very high due to cardiovascular diseases (CVD). Some studies have indicated that cyclosporine A, a drug used to prevent transplant rejection, is associated with bone loss following transplantation. Furthermore, it has an oxidative effect on circulating lipids. Its prooxidant effect on cell membranes causes calcium release. This study aimed to examine whether or not renal transplantation result in improvement in oxidative stress and to assess the association between oxidized LDL (ox-LDL) and some variables in the prediction of CVD risk in Renal Transplantation (RT) patients that were compared with the control group. Material and Methods: A total number of 30 CKD patients were recruited to evaluate time dependent changes in biomarker of OS before and after RT. The ox-LDL, lipid metabolism parameters, CsA, creatinine, calcium and phosphate were assessed both before RT, 10 days and 6 months after RT in comparison with the control group (n = 30). Results: Over 6 months, ox-LDL concentration changed from 79.7 ± 9.7 to 72 ± 7 mU/mL (p < 0.009). calcium phosphate level was positively correlated with the concentration of ox-LDL (R = 0.467, p = 0.011) and cyclosporine (R = 0.419, p = 0.024) 6 months after transplantation. Conclusion: The findings indicated that restoring renal function by transplantation, improves uremia induced oxidative stress. calcium phosphate product, as an independent risk factor for CVD, correlates with ox-LDL before RT and 6 months after RT. Calcium phosphate product correlates with cyclosporine in the RT group, too.

摘要
研究目的：接受肾脏替代治疗的慢性肾脏病（CKD，chronic kidney disease）患者，因心血管疾病（CVD，cardiovascular diseases）导致的死亡率居高不下。已有研究表明，用于预防移植排斥反应的环孢素A（cyclosporine A）可引发移植后骨丢失，且对循环脂质具有氧化作用；其对细胞膜的促氧化效应可诱发钙释放。本研究旨在探讨肾移植（RT，renal transplantation）是否可改善氧化应激（oxidative stress）状态，并评估氧化低密度脂蛋白（ox-LDL，oxidized LDL）与相关变量的关联，以此预测肾移植患者的心血管疾病风险，同时设置对照组进行对照分析。
材料与方法：共纳入30例慢性肾脏病患者，用以评估肾移植前后氧化应激标志物的随时间动态变化。分别于肾移植前、移植后10天及6个月时，检测氧化低密度脂蛋白、脂质代谢参数、环孢素A、肌酐、钙及磷水平，并与30例对照者进行比较。
研究结果：术后6个月内，氧化低密度脂蛋白浓度从79.7±9.7 mU/mL降至72±7 mU/mL（p<0.009）。移植后6个月时，钙磷水平与氧化低密度脂蛋白浓度呈正相关（R=0.467，p=0.011），与环孢素A水平亦呈正相关（R=0.419，p=0.024）。
研究结论：本研究结果显示，通过肾移植恢复肾功能可改善尿毒症诱导的氧化应激。作为心血管疾病的独立危险因素，钙磷乘积在肾移植前及移植后6个月时均与氧化低密度脂蛋白水平相关；且肾移植患者的钙磷乘积也与环孢素A水平存在关联。