晚期糖基化终产物与腹膜透析患者不成熟的血管生成和腹膜功能障碍有关。

Advanced glycation end products are associated with immature angiogenesis and peritoneal dysfunction in patients on peritoneal dialysis.

机构信息

Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Perit Dial Int. 2020 Jan;40(1):67-75. doi: 10.1177/0896860819878344.

DOI:10.1177/0896860819878344

PMID:32063152

Abstract

BACKGROUND

Deposition of advanced glycation end products (AGEs) is frequently found in the peritoneum of patients on peritoneal dialysis (PD). Angiogenesis is also observed in the peritoneum. However, the clinical significance of AGEs and angiogenesis in the peritoneum is not fully understood. We evaluated the maturation of capillary vessels and investigated whether AGEs are associated with angiogenesis and peritoneal function in the peritoneal membrane.

METHODS

Peritoneum obtained when PD catheters were removed from 61 patients with PD was analyzed. The peritoneum was immunohistochemically stained with anti-CD34 (for endothelial cells), anti-alpha smooth muscle actin (αSMA) (for pericytes), and anti-AGE antibodies. We defined CD34-positive and αSMA-negative vessels as immature capillary vessels in peritoneal membranes using serial sections. We evaluated the associations between vessel density, peritoneal function (dialysate-to-plasma ratio for creatinine (D/P creatinine)), and the degree of AGE deposition.

RESULTS

AGE accumulation in the interstitium was positively associated with the duration of PD ( < 0.01). AGE accumulation in the interstitium and vascular wall was positively correlated with the use of acidic solution ( < 0.05) and the maximum value of D/P creatinine ( < 0.05). AGE accumulation in the vascular wall was significantly associated with immature capillary density (CD34+/αSMA-) in the peritoneum ( < 0.01). Vessel density was not significantly correlated with the last measurement of D/P creatinine ( = 0.126, = 0.202), However, immature capillary density was positively correlated with the last measurement of D/P creatinine ( < 0.05, = 0.278).

CONCLUSIONS

AGE accumulation is significantly associated with immature angiogenesis and peritoneal dysfunction in patients undergoing PD.

摘要

背景

在腹膜透析（PD）患者的腹膜中经常发现晚期糖基化终产物（AGEs）的沉积。血管生成也在腹膜中观察到。然而，AGEs 和腹膜中血管生成的临床意义尚未完全了解。我们评估了毛细血管的成熟度，并研究了 AGEs 是否与腹膜功能和腹膜中的血管生成有关。

方法

分析了 61 例 PD 患者拔除 PD 导管时获得的腹膜。腹膜用抗 CD34（内皮细胞）、抗α平滑肌肌动蛋白（αSMA）（周细胞）和抗 AGE 抗体进行免疫组织化学染色。我们使用连续切片将 CD34 阳性和αSMA 阴性的血管定义为腹膜中的不成熟毛细血管。我们评估了血管密度、腹膜功能（肌酐透析液-血浆比（D/P 肌酐））和 AGE 沉积程度之间的相关性。

结果

间质中 AGE 的积累与 PD 的持续时间呈正相关（<0.01）。间质和血管壁中 AGE 的积累与酸性溶液的使用呈正相关（<0.05）和 D/P 肌酐的最大值呈正相关（<0.05）。血管壁中 AGE 的积累与腹膜中不成熟的毛细血管密度（CD34+/αSMA-）显著相关（<0.01）。血管密度与 D/P 肌酐的最后一次测量无显著相关性（=0.126，=0.202），但不成熟的毛细血管密度与 D/P 肌酐的最后一次测量呈正相关（<0.05，=0.278）。