Key result
Urinary extracellular vesicle AGP1 levels accurately identified patients with primary aldosteronism, demonstrating an area under the curve of 0.92 (95% CI 0.82-1; P=0.0055).
Why the study?
Due to the complexity of diagnosing primary aldosteronism using the aldosterone-to-renin ratio and confirmatory studies, novel biomarkers are needed.
Does proteomic profiling of urinary extracellular vesicles identify novel biomarkers for primary aldosteronism?
Case-Control (n=15)
Does proteomic profiling of urinary extracellular vesicles identify novel biomarkers for primary aldosteronism?
Effect estimate: AUC 0.92 (95% CI 0.82 to 1)
p-value: p=0.0055
Proteomic analysis of urinary extracellular vesicles identifies AGP1 as a promising novel biomarker for primary aldosteronism.
May facilitate noninvasive primary aldosteronism diagnosis; leaves open validation in larger prospective cohorts.
CONTEXT: Primary aldosteronism (PA) represents 6% to 10% of all essential hypertension patients and is diagnosed using the aldosterone-to-renin ratio (ARR) and confirmatory studies. The complexity of PA diagnosis encourages the identification of novel PA biomarkers. Urinary extracellular vesicles (uEVs) are a potential source of biomarkers, considering that their cargo reflects the content of the parent cell. OBJECTIVE: We aimed to evaluate the proteome of uEVs from PA patients and identify potential biomarker candidates for PA. METHODS: Second morning spot urine was collected from healthy controls (n = 8) and PA patients (n = 7). The uEVs were isolated by ultracentrifugation and characterized. Proteomic analysis on uEVs was performed using LC-MS Orbitrap. RESULTS: Isolated uEVs carried extracellular vesicle markers, showed a round shape and sizes between 50 and 150 nm. The concentration of uEVs showed a direct correlation with urinary creatinine (r = 0.6357; P = 0.0128). The uEV size mean (167 ± 6 vs 183 ± 4nm) and mode (137 ± 7 vs 171 ± 11nm) was significantly smaller in PA patients than in control subjects, but similar in concentration. Proteomic analysis of uEVs from PA patients identified an upregulation of alpha-1-acid glycoprotein 1 (AGP1) in PA uEVs, which was confirmed using immunoblot. A receiver operating characteristic curve analysis showed an area under the curve of 0.92 (0.82 to 1; P = 0.0055). CONCLUSION: Proteomic and further immunoblot analyses of uEVs highlights AGP1 as potential biomarker for PA.
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Barros et al. (2021) conducted a case-control in Primary aldosteronism (n=15). Primary aldosteronism vs. Healthy controls was evaluated on Diagnostic accuracy of AGP1 as a biomarker for primary aldosteronism (AUC 0.92, 95% CI 0.82 to 1, p=0.0055). Urinary extracellular vesicle AGP1 levels accurately identified patients with primary aldosteronism, demonstrating an area under the curve of 0.92 (95% CI 0.82-1; P=0.0055).
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