Chinese Journal of Nephrology, Dialysis & Transplantation

ISSN 1006-298X      CN 32-1425/R

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Chinese Journal of Nephrology, Dialysis & Transplantation ›› 2026, Vol. 35 ›› Issue (3): 208-214.DOI: 10.3969/j.issn.1006-298X.2026.03.002

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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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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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