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

Xi Xia; Suchun Li; Zhipeng Wang; Siyang Ye; Yuting Fan; Wenxing Peng; Wenfang Chen; Fengxian Huang; Ruihan Tang; Wei Chen

doi:10.1016/j.ekir.2024.01.008

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

Kidney Int Rep. 2024 Jan 10;9(4):1040-1046. doi: 10.1016/j.ekir.2024.01.008. eCollection 2024 Apr.

Authors

Xi Xia^{1

2}, Suchun Li^{1

2}, Zhipeng Wang^{1

2}, Siyang Ye^{1

2}, Yuting Fan^{1

2}, Wenxing Peng^{1

2}, Wenfang Chen³, Fengxian Huang^{1

2}, Ruihan Tang^{1

2}, Wei Chen^{1

2}

Affiliations

¹ Department of Nephrology, The First Affiliated Hospital of Sun Yat-Sen University, People's Republic of China.
² NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, People's Republic of China.
³ Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, People's Republic of China.

Abstract

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.

Keywords: death; end stage renal disease; exostosin; membranous lupus nephritis; outcomes; renal biopsy.