Glomerular Exostosin-Positivity is Associated With Disease Activity and Outcomes in Patients With Membranous Lupus Nephritis.

Introduction: The relationship of exostosin 1 and exostosin 2 (EXT1/EXT2) expression and outcomes in membranous lupus nephritis (MLN) was controversial.
Methods: EXT1/EXT2 was performed by immunohistochemistry (IHC) in 283 consecutive patients with MLN. Clinicopathological characteristics and outcomes of EXT1/EXT2-positive patients were compared with EXT1/EXT2-negative patients. The primary end points were adverse renal events, including death, dialysis, and renal transplantation.
Results: Of the patients with MLN, 29.3% were positive for EXT1/EXT2. The prevalence of EXT1/2-positive MLN was significantly higher in pure class V MLN than those for mixed class V MLN (44.2% vs. 19.4%, P  < 0.001). For EXT1/EXT2-positive patients, the median time between onset of lupus and renal biopsy, and lupus nephritis and renal biopsy is shorter (6 [interquartile range, IQR: 2-25] months vs. 12 [IQR: 3-49] months, P  = 0.008 and 3 [IQR: 2-18] months vs. 6 [IQR: 2-23] months, P  = 0.039) and they had significantly lower systemic lupus erythematosus Disease Activity Index (SLEDAI) scores ( P  = 0.015) and lower serum creatinine levels ( P  < 0.001), higher hemoglobin ( P  = 0.006) as well as lower blood pressure. The EXT1/EXT2-positive patients had significantly fewer chronicity features (glomerulosclerosis, P  < 0.001; interstitial fibrosis, P  = 0.006; and tubular atrophy, P  = 0.002) and fewer activity indicators (endocapillary hypercellularity, P  = 0.012; cellular crescents, P  = 0.007; and fibrocellular crescents, P  < 0.001) on renal biopsy. After a median follow-up of 65 (28-126) months, EXT1/EXT2-positive patients were less likely to experience adverse renal events (2.4% vs. 16.0%, P  = 0.001).
Conclusion: Compared with EXT1/EXT2-negative patients, the EXT1/EXT2-positive patients presented with lower disease activity and were less likely to experience adverse renal events in relationship with the chronicity index.
(© 2024 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)