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Serum Complement C4 Levels Are a Useful Biomarker for Predicting End-Stage Renal Disease in Microscopic Polyangiitis.

ABSTRACT: This study aimed to evaluate the risk factors for end-stage renal disease (ESRD) in microscopic polyangiitis (MPA). In total, 74 patients with MPA were enrolled, and we compared the baseline clinical characteristics and disease activity between MPA patients who have progressed to ESRD and those without ESRD to select predictive factors for ESRD. Out of 74 patients, 12 patients (16.2%) had ESRD during follow-up. Serum C4 levels were significantly higher in MPA patients who have progressed to ESRD than in those without ESRD (p = 0.009). Multivariate analyses revealed that high serum creatinine levels (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.25-15.5) and high serum C4 levels (OR 1.24, 95% CI 1.03-1.49) were risk factors for ESRD. Using receiver operating characteristic analysis, the cut-off value for initial serum C4 levels and serum creatinine levels were 29.6 mg/dL and 3.54 mg/dL, respectively. Patients with MPA with a greater number of risk factors (serum C4 levels > 29.6 mg/dL and serum creatinine levels > 3.54 mg/dL) had a higher ESRD progression rate. Serum C4 levels were significantly positively correlated with serum creatinine levels and kidney Birmingham vasculitis activity score (p = 0.02 and 0.04, respectively). These results suggest that serum C4 levels are useful tools for assessing renal disease activity and prognosis in MPA.

SUBMITTER: Matsuda S

PROVIDER: S-EPMC10572948 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Serum Complement C4 Levels Are a Useful Biomarker for Predicting End-Stage Renal Disease in Microscopic Polyangiitis.

Matsuda Shogo S Oe Katsumasa K Kotani Takuya T Okazaki Ayana A Kiboshi Takao T Suzuka Takayasu T Wada Yumiko Y Shiba Hideyuki H Hata Kenichiro K Shoda Takeshi T Takeuchi Tohru T

International journal of molecular sciences 20230922 19

This study aimed to evaluate the risk factors for end-stage renal disease (ESRD) in microscopic polyangiitis (MPA). In total, 74 patients with MPA were enrolled, and we compared the baseline clinical characteristics and disease activity between MPA patients who have progressed to ESRD and those without ESRD to select predictive factors for ESRD. Out of 74 patients, 12 patients (16.2%) had ESRD during follow-up. Serum C4 levels were significantly higher in MPA patients who have progressed to ESRD ...[more]

PMID: 37833884

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Project description:ObjectivesMicroscopic 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.MethodsFirstly, 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.ResultsDuring 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.ConclusionsIn 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.

Project description:BackgroundProteasomes are found in both the cell nucleus and cytoplasm and play a major role in the ubiquitin-dependent and -independent non-lysosomal pathways of intracellular protein degradation. Proteasomes are also involved in the turnover of various regulatory proteins, antigen processing, cell differentiation, and apoptosis. To determine the diagnostic value of serum proteasome in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), we investigated patients with AAV at various stages of the disease.MethodsSerum 20S-proteasome was measured by ELISA in 44 patients with MPO-ANCA-associated microscopic polyangiitis (MPA) and renal involvement. Thirty of the patients provided serum samples before the initial treatment, and 30 provided samples during remission; 16 provided samples at both time points.ResultsThe mean serum 20S-proteasome level was significantly higher in the active-vasculitis patients (3414.6 ± 2738.9 ng/mL; n = 30) compared to the inactive-vasculitis patients (366.4 ± 128.4 ng/mL; n = 30; p < 0.0001) and 40 controls (234.9 ± 90.1 ng/mL; p < 0.0001). There were significant positive correlations between the serum 20S-proteasome level and the Birmingham Vasculitis Activity Score (BVAS) (r = 0.581, p < 0.0001), the ANCA titer (r = 0.384, p < 0.0001), the white blood cell (WBC) count (r = 0.284, p = 0.0042), the platelet count (r = 0.369, p = 0.0002), and the serum C-reactive protein (CRP) level (r = 0.550, p < 0.0001). There were significant negative correlations between the serum 20S-proteasome level and both the hemoglobin concentration (r = - 0.351, p = 0.0003) and the serum albumin level (r = - 0.460, p < 0.0001). In a multiple regression analysis, there was a significant positive correlation between the serum 20S-proteasome level and only the BVAS results (β = 0.851, p = 0.0009). In a receiver operating curve analysis, the area under the curve for the serum 20S-proteasome level was 0.996, which is higher than those of the WBC count (0.738) and the serum CRP level (0.963).ConclusionThe serum level of 20S-proteasome may be a useful marker for disease activity in AAV.

Dataset Information

Serum Complement C4 Levels Are a Useful Biomarker for Predicting End-Stage Renal Disease in Microscopic Polyangiitis.

Publications

Serum Complement C4 Levels Are a Useful Biomarker for Predicting End-Stage Renal Disease in Microscopic Polyangiitis.

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