Urinary activated leukocyte cell adhesion molecule as a novel biomarker of lupus nephritis histology

Abstract

Background: Lupus nephritis (LN) is one of the most severe complications of SLE patients. We aim to validate urinary ALCAM as a biomarker in predicting renal disease histpathology in a Chinese lupus cohort.

Methods: In this cross-sectional study, a total of 256 patients and controls were recruited. Urinary levels of ALCAM were determined by ELISA. Renal histopathology was reviewed by an experienced renal pathologist.

Results: Urinary ALCAM levels were significantly increased in active LN patients when compared to active SLE patients without renal involvement (p < 0.001), inactive LN patients (p = 0.023), inactive SLE patients without renal involvement (p < 0.001), and healthy controls (p < 0.001). Correlation analysis revealed a positive correlation between urinary ALCAM and general disease activity-SLEDAI score (r = 0.487, p < 0.001), as well as renal disease activity-rSLEDAI (r = 0.552, p < 0.001) and SLICC RAS (r = 0.584, p < 0.001). Urinary ALCAM also correlated with lab parameters including 24-h urine protein, hemoglobin, and complement 3. Moreover, urinary ALCAM levels were significantly increased in class III and IV (proliferative) LN as compared to those in class V (membranous) LN. It outperformed conventional biomarkers (anti-dsDNA antibody, C3, C4, proteinuria) in discriminating the two groups of LN. On renal histopathology, urinary ALCAM levels correlated positively with activity index (r = 0.405, p < 0.001) but not chronicity index (r = 0.079, p = 0.448).

Conclusion: Urinary ALCAM is a potential biomarker for predicting renal pathology activity in LN and may serve as a valuable surrogate marker of renal histopathology.

Keywords: ALCAM; Activity index; Chronicity index; Lupus nephritis; Renal histopathology; Urinary biomarker.

Fig. 1

Urinary ALCAM levels were elevated in active LN patients. a Significant increase of urinary ALCAM in aLN patients (11.50 IQR (16.79) ng/mg) when compared to those in aNR (3.51 IQR (6.20) ng/mg), iLN (3.46 IQR (5.14) ng/mg), iNR (2.45 IQR (4.04) ng/mg), and HC (1.79 IQR (1.23) ng/mg). b Receiver operating characteristic curve analysis of urinary ALCAM in discriminating aLN from aNR, iLN, and HC. aLN, active LN; aNR, active SLE without renal involvement; iLN, inactive LN; iNR, inactive SLE without renal involvement; HC, healthy control; AUC, area under the curve. *p < 0.05; ***p < 0.001

Fig. 2

Correlation between urinary ALCAM and a SLEDAI, b rSLEDAI, c SLICC RAS, d serum creatinine, e 24-h urine protein, f serum albumin, g hemoglobulin, and h complement 3. SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; rSLEDAI, renal SLEDAI; SLICC RAS, SLICC renal activity score; Cr, creatinine; 24-h UP, 24-h urine protein; AIb, serum albumin; Hb, hemoglobin; C3, complement 3

Fig. 3

Urinary ALCAM levels were elevated in proliferative LN patients. a Group comparison between proliferative (class III/IV ± V) LN patients (14.10 IQR (18.21) ng/mg) and membranous (class V) LN patients (4.70 IQR (4.56) ng/mg). b Receiver operating characteristic curve analysis of urinary ALCAM in distinguishing proliferative LN from membranous LN. LN, lupus nephritis; AUC, area under the curve

Fig. 4

Correlation analysis between urinary ALCAM and a AI and b CI in renal histopathology. AI, activity index; CI, chronicity index