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

Abstract

IntroductionThe relationship of Exostosin 1 and Exostosin 2 (EXT1/EXT2) expression and outcomes in membranous lupus nephritis (MLN) was controversial. MethodsEXT1/EXT2 was performed by immunohistochemistry in 283 consecutive MLN patients. Clinicopathological characteristics and outcomes of EXT1/EXT2-positive patients were compared with EXT1/EXT2-negative patients.The primary endpoints were adverse renal events include death, dialysis and renal transplantation. Results29.3% MLN patients 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, For EXT1/EXT2-positive patients, the median time between onset of lupus and renal biopsy, and lupus nephritis and renal biopsy is shorter [6 (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 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, fibrocellular crescents, P=0.007 and cellular 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). ConclusionCompared 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.