Serum Soluble Receptors for Advanced Glycation End-Products May Predict Mortality in Microscopic Polyangiitis and Granulomatosis with Polyangiitis

• Published in: Yonsei medical journal Vol. 65; no. 11; pp. 651 - 660
• Main Authors: Yoon, Taejun, Ahn, Sung Soo, Ha, Jang Woo, Ko, Eunhee, Song, Jason Jungsik, Park, Yong-Beom, Lee, Sang-Won
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.11.2024; 연세대학교의과대학
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers - blood; Female; Granulomatosis with Polyangiitis - blood; Granulomatosis with Polyangiitis - diagnosis; Granulomatosis with Polyangiitis - mortality; Humans; Male; Microscopic Polyangiitis - blood; Microscopic Polyangiitis - diagnosis; Microscopic Polyangiitis - mortality; Middle Aged; Original; Proportional Hazards Models; Receptor for Advanced Glycation End Products - blood; 의학일반; granulomatosis with polyangiitis; mortality; Soluble; microscopic polyangiitis; receptors for advanced glycation end products
• ISSN: 0513-5796; 1976-2437; 1976-2437
• DOI: 10.3349/ymj.2023.0466

This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.