LECT-2对腹膜透析患者腹膜及残肾功能下降的预测价值及临床意义

The Predictive Value and Clinical Significance of LECT-2 in the Decline of Peritoneal and Residual Renal Function in Peritoneal Dialysis Patients

摘要: 目的：本研究纳入不同透析龄的腹膜透析患者，检测腹透液中白细胞衍生趋化因子-2 (LECT-2)、转化生长因子-β (TGF-β)、纤连蛋白(FN)等指标，收集临床数据，采用统计学方法分析LECT-2与TGF-β、FN及临床指标的相关性，旨在研究不同透析龄腹膜透析患者腹透液中LECT-2的表达水平的差异，并探讨其与TGF-β、FN等纤维化指标及临床参数的相关性，以评估LECT-2在腹膜纤维化进程中的潜在作用及临床意义。方法：本研究纳入136例肾脏内科规律随访的持续性不卧床腹膜透析(PD)患者为研究对象。根据实际透析龄(PD治疗起始至入组时间)，采用分层分组法分为4组，收集腹膜透析液，采用酶联免疫吸附法检测LECT-2、TGF-β和FN的表达水平，并收集同期临床资料，根据数据是否服从正态分布，采用Spearman、Pearman检验等进行相关性分析。通过每日腹腔注射高糖透析液构建小鼠腹膜纤维化模型，并对小鼠腹膜组织进行HE染色、Masson染色及免疫组织化学染色。观察小鼠腹膜组织病理学变化及腹膜纤维化相关分子表达，采用SPSS 26.0统计软件完成数据的统计分析工作，运用GraphPad Prism 10.0绘图软件进行实验结果的图表绘制。结果：透析龄 > 5年的腹膜透析患者腹透液中LECT-2浓度显著升高，且LECT-2水平与经典促纤维化因子TGF-β及细胞外基质产物FN均呈显著正相关(r = 0.267, P = 0.017; r = 0.363, P = 0.0008)，提示LECT-2可能参与长期腹膜透析相关腹膜纤维化进程。相关性分析表明，LECT-2与残余肾功能(残肾Kt/V、残肾Ccr)呈强负相关(r = −0.41, P < 0.001)，即LECT-2水平越高，残余肾功能丢失越显著。同时，LECT-2与β2-微球蛋白、血钙呈正相关，提示其水平升高与尿毒症毒素蓄积及代谢负荷加重密切相关。高糖腹透液诱导的腹膜纤维化小鼠腹膜组织中LECT-2、TGF-β及FN表达均显著增强，进一步支持LECT-2与腹膜纤维化的病理关联。结论：本研究显示，腹透液中LECT-2水平随腹膜透析龄延长而升高，并与TGF-β、FN呈正相关，同时与残肾功能下降及尿毒症相关代谢指标改变存在关联，提示LECT-2可能参与腹膜透析相关腹膜纤维化进程。本研究为横断面观察性研究，仅能揭示指标间的相关性，无法确立因果关系，LECT-2作为腹膜损伤与残肾功能衰退的潜在生物学标志，仍需前瞻性队列研究与机制实验进一步验证其临床价值与作用机制。

Abstract: Objective: This study enrolled peritoneal dialysis (PD) patients with different dialysis vintages to detect the levels of leukocyte-derived chemokine-2 (LECT-2), transforming growth factor-β (TGF-β), fibronectin (FN) and other biomarkers in peritoneal dialysate, and to collect relevant clinical data. Statistical methods were applied to analyze the correlations of LECT-2 with TGF-β, FN and clinical parameters. This study aimed to compare the differences in peritoneal dialysate LECT-2 expression among PD patients with varying dialysis durations, and to explore its correlations with fibrotic indicators (TGF-β, FN) and clinical variables, so as to evaluate the potential role and clinical significance of LECT-2 in the progression of peritoneal fibrosis. Methods: A total of 136 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with regular follow-up in the nephrology department were included as research subjects. According to the actual dialysis vintage (duration from initial PD initiation to enrollment), all patients were divided into four groups via stratified grouping. Peritoneal dialysate samples were collected, and the expression levels of LECT-2, TGF-β and FN were determined by enzyme-linked immunosorbent assay (ELISA). Synchronous clinical data were also collected. Spearman’s correlation or Pearson’s correlation test was adopted for correlation analysis based on the normality of data distribution. A mouse model of peritoneal fibrosis was established by daily intraperitoneal injection of high-glucose dialysate. Hematoxylin-eosin (HE) staining, Masson staining and immunohistochemical staining were performed on mouse peritoneal tissues to observe histopathological changes and the expression of fibrosis-related molecules. SPSS 26.0 software was used for statistical analysis, and GraphPad Prism 10.0 software was applied for plotting all experimental results. Results: The concentration of LECT-2 in peritoneal dialysate was significantly elevated in PD patients with dialysis vintage over 5 years. LECT-2 levels were positively correlated with the classic pro-fibrotic factor TGF-β and extracellular matrix product FN (r = 0.267, P = 0.017; r = 0.363, P = 0.0008), suggesting that LECT-2 may be involved in the progression of long-term PD-associated peritoneal fibrosis. Correlation analysis revealed that LECT-2 was strongly negatively correlated with residual renal function (residual renal Kt/V and residual renal Ccr) (r = −0.41, P < 0.001), indicating that higher LECT-2 levels were accompanied by more severe loss of residual renal function. Meanwhile, LECT-2 was positively correlated with β2-microglobulin and serum calcium, which demonstrated that the upregulation of LECT-2 was closely associated with uremic toxin accumulation and aggravated metabolic burden. In the high-glucose dialysate-induced peritoneal fibrosis mouse model, the expression of LECT-2, TGF-β and FN in peritoneal tissues was markedly upregulated, which further confirmed the pathological association between LECT-2 and peritoneal fibrosis. Conclusion: The level of LECT-2 in peritoneal dialysate increases with the prolongation of PD duration, and is positively correlated with TGF-β and FN. Additionally, LECT-2 is closely linked to the decline of residual renal function and alterations in uremia-related metabolic indicators. These findings indicate that LECT-2 may participate in the pathogenesis of PD-related peritoneal fibrosis. As a cross-sectional observational study, the current research can only clarify the correlations between indicators rather than establish causal relationships. Further prospective cohort studies and mechanistic experiments are required to verify the clinical value and specific molecular mechanism of LECT-2 as a potential biomarker for peritoneal injury and residual renal function deterioration.