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The association between serum lipids at diagnosis and renal outcome in microscopic polyangiitis patients
Zigui Zheng1,2,3, Yujia Wang1,2,3, Jingzhi Xie1,2,3
1Department of Nephrology, Blood Purification Research Center, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
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.
Insights
High triglycerides (TG) and very low-density lipoprotein (VLDL) levels at diagnosis are linked to worse kidney outcomes in microscopic polyangiitis (MPA). Elevated levels increase the risk of end-stage renal disease (ESRD) in MPA patients.
Area of Science:
- Nephrology
- Immunology
- Cardiology
Background:
- Microscopic polyangiitis (MPA) is a form of ANCA-associated vasculitis (AAV) causing endothelial damage.
- Dyslipidemia is implicated in vascular injury, but its impact on MPA renal prognosis is unclear.
Purpose of the Study:
- To investigate the association between blood lipid levels at diagnosis and renal prognosis in MPA patients.
- To explore the mechanisms linking high triglycerides to poor renal outcomes in MPA.
Main Methods:
- Retrospective analysis of 110 MPA patients with end-stage renal disease (ESRD) as the primary endpoint.
- Cox regression and survival analysis for lipid-outcome association; DIA quantitative proteomics for mechanistic insights.
Main Results:
- 40% of patients developed ESRD over a median 23-month follow-up.
- High serum triglycerides (TG >1.45 mmol/L) at diagnosis independently predicted ESRD.
- Elevated TG levels correlated with upregulated profibrotic, inflammatory, complement, and coagulation pathways.
Conclusions:
- Elevated serum TG and VLDL at diagnosis are associated with increased ESRD risk in MPA.
- Potential mechanisms involve profibrotic and inflammatory pathways, plus complement and coagulation cascade activation.
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