TY - JOUR
T1 - In patients with membranous lupus nephritis, exostosin-positivity and exostosin-negativity represent two different phenotypes
AU - Ravindran, Aishwarya
AU - Moura, Marta Casal
AU - Fervenza, Fernando C.
AU - Nasr, Samih H.
AU - Alexander, Mariam P.
AU - Fidler, Mary E.
AU - Herrera Hernandez, Loren P.
AU - Zhang, Pingchuan
AU - Grande, Joseph P.
AU - Cornell, Lynn D.
AU - Gross, Lou Ann
AU - Negron, Vivian
AU - Jenson, Grace E.
AU - Madden, Benjamin J.
AU - Cristine Charlesworth, M.
AU - Sethi, Sanjeev
N1 - Publisher Copyright:
Copyright © 2021 by the American Society of Nephrology
PY - 2021/3
Y1 - 2021/3
N2 - Background In patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis. Methods We conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared. Results Our study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger (P50.01), had significantly lower serum creatinine levels (P50.02), were significantly more likely to present with proteinuria $3.5 g/24 h (P50.009), and had significantly less chronicity features (glomerulosclerosis, P50.001 or interstitial fibrosis and tubular atrophy, P,0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1/EXT2-positive and 96 (60%) were EXT1/EXT2-negative. The proportion of patients with class 3/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1/EXT2-positive and EXT1/ EXT2-negative groups (25.0% versus 32.3%; P50.32). The patients who were EXT1/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1/EXT2-positive patients (18.8% versus 3.1%; P50.003). Conclusions The prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive.
AB - Background In patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis. Methods We conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared. Results Our study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger (P50.01), had significantly lower serum creatinine levels (P50.02), were significantly more likely to present with proteinuria $3.5 g/24 h (P50.009), and had significantly less chronicity features (glomerulosclerosis, P50.001 or interstitial fibrosis and tubular atrophy, P,0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1/EXT2-positive and 96 (60%) were EXT1/EXT2-negative. The proportion of patients with class 3/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1/EXT2-positive and EXT1/ EXT2-negative groups (25.0% versus 32.3%; P50.32). The patients who were EXT1/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1/EXT2-positive patients (18.8% versus 3.1%; P50.003). Conclusions The prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive.
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U2 - 10.1681/ASN.2020081181
DO - 10.1681/ASN.2020081181
M3 - Article
C2 - 33478971
AN - SCOPUS:85102111136
SN - 1046-6673
VL - 32
SP - 695
EP - 706
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 3
ER -