肾脏病与透析肾移植杂志

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肾脏病与透析肾移植杂志 ›› 2026, Vol. 35 ›› Issue (3): 208-214.DOI: 10.3969/j.issn.1006-298X.2026.03.002

• 论著 • 上一篇    下一篇

尿液富含亮氨酸重复神经元蛋白 4 水平与糖尿病肾病表型关联分析

  

  • 出版日期:2026-06-29 发布日期:2026-07-02

Association analysis of urinary leucine-rich repeat neuronal4 levels with clinical and pathological phenotypes in diabetic nephropathy

  • Online:2026-06-29 Published:2026-07-02

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摘要： 目的：采用横断面研究设计，探索尿液富含亮氨酸重复神经元蛋白4(LRRN4)与糖尿病肾病患者临床表型和肾脏病理表型关系，评估尿液LRRN4对糖尿病肾病病理表型的预判价值。 方法：利用经肾活检诊断明确的糖尿病肾病患者肾组织样本，观察肾组织中LRRN4表达与临床及病理表型的相关性；C-index分析尿液LRRN4表达对肾脏病理指标的预判价值。  结果：糖尿病肾病患者肾组织中LRRN4富集表达于肾小管，其表达随着疾病分期而逐渐增加，不仅与糖尿病肾病患者血清肌酐(SCr)(r=0.55,P<0.0001)、24h尿蛋白定量水平显著正相关(r=0.65,P<0.0001); 也与肾小管萎缩和间质纤维化 (IFTA)(r=0.74,P<0.0001)、肾小球硬化 (r=0.72,P<0.0001)、间质炎症(r=0.64,P<0.0001) 显著正相关。尿液LRRN4表达与肾组织蛋白表达具有良好相关性，其水平与SCr(r=0.41,P=0.0001)、24h尿蛋白定量呈显著正相关(r=0.60,P<0.0001), 也与IFTA(r=0.47,P<0.0001)、肾小球硬化(r=0.49,P<0.0001) 及间质炎症 (r=0.5,P<0.0001) 显著正相关。基于尿液LRRN4、SCr和 24h尿蛋白定量构建的联合诊断模型，可以较好评估IFTA、肾小球硬化及间质炎症程度，其对应的C-index值分别为 [0.963(95% CI 0.928~0.998)]、[0.911(95% CI 0.849~0.974)]、[0.922(95% CI 0.860~0.948)]。  结论：糖尿病肾病患者尿液LRRN4表达显著增加，且有望成为反映其肾脏病理病变严重程度的新型无创性分子标志物。

关键词: 糖尿病肾病, 富含亮氨酸重复神经元蛋白 4, 病理指标, 生物标志物

Abstract: Objective: A cross-sectional study was conducted to investigate the associations of urinary leucine-rich repeat neuronal protein 4 (LRRN4) with the clinical and renal pathological phenotypes of patients with diabetic nephropathy (DN), and to evaluate the diagnostic value of urinary LRRN4 as a biomarker of pathological features in DN.

Methods: In a biopsy-proven DN cohort, we examined the relationship between renal LRRN4 expression and both clinical and pathological phenotypes. The C-index was applied to assess the diagnostic performance of urinary LRRN4 for renal pathological indicators.
Results: In patients with DN, LRRN4 was highly enriched in renal tubules, and its expression progressively increased with disease progression. Renal LRRN4 expression was positively correlated with serum creatinine levels (r=0.55, P<0.0001), 24-hour urinary protein excretion (r=0.65, P<0.0001), interstitial fibrosis and tubular atrophy (IFTA) (r=0.74, P<0.0001), glomerulosclerosis (r=0.72, P<0.0001), and interstitial inflammation (r=0.64, P<0.0001). Urinary LRRN4 levels were well correlated with its protein expression in renal tissues. Its concentration was significantly positively correlated with SCr (r=0.41, P=0.0001), 24-hour urinary protein quantification (r=0.60, P<0.0001), IFTA (r=0.47, P<0.0001), glomerulosclerosis (r=0.49, P<0.0001) and interstitial inflammation (r=0.50, P<0.0001). The combined diagnostic model established based on urinary LRRN4, SCr and 24-hour urinary protein quantification effectively evaluated the severity of IFTA, glomerulosclerosis and interstitial inflammation, with C-index values of [0.963 (95%CI 0.928~0.998)], [0.911 (95%CI 0.849~0.974)] and [0.922 (95%CI 0.860~0.948)].
Conclusion: Urinary LRRN4 protein levels are significantly increased in patients with DN and may serve as a noninvasive biomarker reflecting renal pathological changes in DN.

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