血清晚期糖基化终末产物与终末期肾病患者向肾替代治疗过渡期间内皮功能障碍和低度炎症的关系

    Relationship between serum advanced glycation end products and endothelial dysfunction and low-grade inflammation in patients with end-stage renal disease during a transition into renal replacement therapy

      摘要
    • 摘要:
      目的  探讨血清晚期糖基化终末产物（advanced glycation end products，AGEs）与终末期肾病患者向肾替代治疗过渡期间内皮功能障碍（endothelial dysfunction，ED）和低度炎症（low grade inflammation，LGI）的关系。
      方法  这项横断面观察性研究包括2016年2月至2021年7月在武汉科技大学附属孝感医院计划进行透析或肾移植的慢性肾脏病5期非透析（chronic kidney disease stage 5 non-dialysis，CKD5-ND）患者，另外纳入50名健康体检人群数据作为对照。采用超高效液相色谱串联质谱法测量血清游离和蛋白质结合型AGEs水平，包括Nε-（羧甲基）赖氨酸（carboxymethyl lysine，CML）、 Nε-（羧乙基）赖氨酸（carboxylethyl lysine，CEL）、Nδ-（5-氢-5-甲基-4咪唑酮-2-基）鸟氨酸（5-hydro-5-methyl-4-imidazolon-2-yl ornithine，MG-H1），并通过皮肤自发荧光评估组织AGEs堆积。此外，检测血清ED和LGI生物标志物。
      结果 所有CKD5-ND患者血清游离CML、蛋白结合型CML、游离CEL、蛋白结合型CEL、游离MG-H1、蛋白结合型MG-H1水平分别为1142.2（765.1，1538.3）nmol/L、197.3（163.1，256.6）nmol、734.7（520.2，939.4）nmol/L、58.0（41.8，74.3）nmol、2244.4（1670.2，3154.6）nmol/L、59.1（47.6，69.9）nmol，均高于对照组（P＜0.05）。在未经校正的分析中，血清游离CML高水平与更高的ED综合评分和LGI综合评分相关（P＜0.05）。同样地，血清游离CEL高水平、蛋白结合型MG-H1高水平与更高的LGI综合评分相关（P＜0.05）。但是在校正年龄、性别、治疗史和疾病史后，只有血清游离CML是影响ED综合评分的独立危险因素（P＜0.05）。进一步校正应用慢性肾脏病流行病合作工作组公式估算的肾小球滤过率（estimate glomerular filtration rate of the chronic kidney disease epidemiology collaboration, eGFRCKD-EPI）后，血清游离CML与LGI综合评分也无相关性（P=0.166）。
      结论 在CKD5-ND患者中，校正年龄、性别、治疗史和疾病史后，血清AGEs水平升高与CKD5-ND患者ED和LGI相关，但在额外校正eGFR后，则降低了这一相关性，表明eGFR混杂和（或）校正了血清AGEs与ED和LGI的关系。

       

      Abstract:
      Objective  To explore the relationship between serum advanced glycation end products（AGEs）, endothelial dysfunction（ED） and low-grade inflammation（LGI） in patients with end-stage renal disease（ESRD） during a transition into renal replacement therapy.
      Methods  For this cross-sectional observational study, clinical data were reviewed for chronic kidney disease stage 5 non-dialysis（CKD5-ND） patients scheduled for dialysis or renal transplantation from February 2016 to July 2021. In addition, 50 health checkups were included as controls. Serum levels of free and protein-bound AGEs were measured by ultra-high performance liquid chromatography（UPLC） tandem mass spectrometry（MS）. Nε-（carboxymethyl） lysine（CML）, Nε-（carboxyethyl） lysine（CEL）, Nδ-（5-hydro-5-methyl-4-imidazolon-2-yl） ornithine （MG-H1） and tissue AGEs accumulation were evaluated by skin autofluorescence（SAF）. In addition, serum ED and LGI biomarkers were detected.
      Results  Serum levels of free CML, protein binding CML, free CEL, protein binding CEL, free MG-H1 and protein binding MG-H1 in all CKD5-ND patients were 1142.2（765.1, 1538.3） nmol/L, 197.3（163.1, 256.6） nmol, 734.7（520.2, 939.4） nmol/L, 58.0（41.8, 74.3） nmol, 2244.4（1670.2, 3154.6） nmol/L and 59.1（47.6, 69.9） nmol. All parameters were higher than those in control group（P＜0.05）. In unadjusted analyses, high levels of serum free CML were associated with higher ED/LGI composite scores（P＜0.05）. Similarly, high levels of serum free CEL and protein-bound MG-H1 were associated with higher LGI composite scores（P＜0.05）. However, after adjusting for age, gender, treatment history and disease history, only serum free CML was an independent risk factor affecting the comprehensive ED score（P＜0.05）. After further adjustment for estimate glomerular filtration rate of the chronic kidney disease epidemiology collaboration, serum free CML was not associated with LGI composite score（P = 0.166）.
      Conclusion  After adjusting for age, gender, treatment history and disease history, elevated serum AGE level is associated with ED/LGI in CKD5-ND patients. However, after adjusting for eGFR, this correlation become weaker, suggesting that eGFR confounding and/or adjusting for the relationship between serum AGEs and ED/LGI.

       

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