Abstract
OBJECTIVES: Microscopic polyangiitis (MPA) is a subgroup of ANCA-associated vasculitis (AAV), which is characterized by vascular endothelial cell damage caused by abnormally activated neutrophils. Dyslipidemia is associated with vascular endothelial cell injury, and the relationship between blood lipid levels and renal prognosis in MPA patients is not clear. We aim to investigate the correlation between blood lipid levels at diagnosis and renal prognosis in MPA patients. METHODS: Firstly, we retrospectively included 110 patients diagnosed with MPA and the primary endpoint was the occurrence of end stage renal disease (ESRD). The association between blood lipids at diagnosis and renal outcome was evaluated with Cox regression analysis and survival analysis. Secondly, we explored the potential underlying mechanism of poor renal prognosis in patients with high triglycerides (TG) levels at diagnosis using data independent acquisition (DIA) quantitative proteomics. RESULTS: During a median follow-up period of 23 months, 44 out of 110 patients (40%) developed ESRD. High serum TG at diagnosis was associated with ESRD development after adjusting for several confounding factors including age, gender, body mass index (BMI), hypertension, diabetes mellitus, estimated glomerular filtration rate (eGFR) and Birmingham Vasculitis Activity Score (BVAS). Serum very low-density lipoprotein (VLDL) demonstrated a marginal trend towards association with ESRD development. MPA patients with TG >1.45 mmol/L or VLDL > 0.66 mmol/L had significantly higher risk of ESRD development than those with TG ≤ 1.45 mmol/L or VLDL ≤ 0.66 mmol/L. DIA quantitative proteomics analysis suggested that patients with elevated TG levels and severe MPA had an upregulation of profibrotic pathways, inflammatory signaling, and complement and coagulation cascades, in contrast to those with lower TG levels and milder disease severity. CONCLUSIONS: In MPA patients, high TG or VLDL at diagnosis is associated with an increased risk of ESRD development. The potential mechanisms may be associated with the upregulation of profibrotic and inflammatory signaling pathways, and the activation of complement and coagulation cascades.