Department and Clinic of Pediatric Nephrology, Wroclaw Medical University, Poland.
Adv Clin Exp Med. 2020 Sep;29(9):1083-1090. doi: 10.17219/acem/123350.
Kidney injury in the course of chronic kidney disease (CKD) is a consequence of aggravated cell migration, inflammation, apoptosis, and fibrosis. However, the sequence of these phenomena, as well as of the reparatory mechanisms, are not fully known. Monocyte chemoattractant protein 1 (MCP-1) and macrophage colony-stimulating factor (MCSF) trigger monocyte migration to the sites of inflammation and their transition into macrophages. Tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) plays a protective role against excessive matrix remodeling, whereas survivin is known for its anti-apoptotic activity.
To analyze the serum, urine and fractional excretion (FE) values of MCP1, MCSF, TIMP-2, and survivin in children at subsequent stages of CKD being treated conservatively, and to analyze the potential applicability of these markers in the evaluation of CKD-related renal damage and protective mechanisms against it.
The study group consisted of 70 children with conservatively treated CKD, stages 1-5, and 12 controls. The serum and urine concentrations of MCP1, MCSF, TIMP-2, and survivin were assessed using enzyme-linked immunosorbent assay (ELISA). The FE of these parameters in the urine was also assessed.
The serum values of all parameters were significantly elevated at CKD stage 1 compared to the controls. The urinary concentrations of MCP-1 and MCSF (stages 1-2) rose earlier than TIMP-2 and survivin (stage 4) concentrations. The FE values started increasing at CKD stage 3 (MCP-1) or stage 4 (other parameters).
The complex analysis of serum/urinary/FE values of the selected parameters revealed a sequence of multifaceted CKD-related phenomena, when the migration of cells and inflammation were followed by delayed and insufficient anti-fibrotic and anti-apoptotic activity.
慢性肾脏病（CKD）过程中的肾损伤是细胞迁移、炎症、细胞凋亡和纤维化加剧的结果。然而，这些现象的发生顺序以及修复机制尚不完全清楚。单核细胞趋化蛋白 1（MCP-1）和巨噬细胞集落刺激因子（MCSF）触发单核细胞向炎症部位迁移，并促使其向巨噬细胞转化。基质金属蛋白酶组织抑制剂-2（TIMP-2）在防止基质过度重塑方面发挥保护作用，而生存素则具有抗细胞凋亡的活性。
分析接受保守治疗的 CKD 不同阶段儿童的血清、尿液和分数排泄（FE）中 MCP1、MCSF、TIMP-2 和 survivin 的水平，并分析这些标志物在评估 CKD 相关肾损伤和保护机制方面的潜在适用性。
研究组包括 70 名接受保守治疗的 CKD 患儿（1-5 期）和 12 名对照组儿童。采用酶联免疫吸附试验（ELISA）检测 MCP1、MCSF、TIMP-2 和 survivin 的血清和尿液浓度，同时评估这些参数在尿液中的 FE。
与对照组相比，CKD 1 期患儿所有参数的血清值均显著升高。MCP-1 和 MCSF 的尿浓度（1-2 期）早于 TIMP-2 和 survivin 的浓度（4 期）升高。FE 值在 CKD 3 期（MCP-1）或 4 期（其他参数）开始升高。
对选定参数的血清/尿液/FE 值进行综合分析，揭示了 CKD 相关现象的复杂序列，细胞迁移和炎症后出现延迟且不足的抗纤维化和抗细胞凋亡活性。
