LAUSR

Objective: Adrenal venous sampling (AVS) is recognized as the gold standard for subtyping primary aldosteronism (PA), but its invasive nature and technical challenges limit its availability. A recent study reported that sodium chloride cotransporter (NCC) in urinary exosomes is a promising marker for assessing the biological activity of aldosterone and can be treated as a potential biomarker of PA. The current study was conducted to verify the hypothesis that the expression of NCC and its phosphorylated form (pNCC) in urinary exosomes are different in various subtypes and genotypes of PA and can be used to select AVS candidates. Design and method: A total of 27 patients with PA were enrolled in the study.Patients with LI > = 4 and < 4 were classified into high LI (hLI) and low LI (lLI) groups, respectively. Urinary exosomes were isolated from spot urine samples using ultracentrifugation. NCC and pNCC expressions were tested in patients diagnosed with PA who underwent AVS. Sanger sequencing of KCNJ5 was performed on DNA extracted from adrenal adenoma. Results: Compared with the lLI group, the hLI group had higher levels of 24 h urinary aldosterone (28.6 ± 11.8 vs 14.9 ± 4.6, P = 0.0002) and supine PAC (314 ± 115 vs 163 ± 53, P < 0.0001) on admission (Table 1). In addition, the pre-saline infusion test (pre-SIT) supine PAC (after correction of hypokalemia) in the hLI group was higher than that in the lLI group (342 ± 172 vs 224 ± 59, P = 0.0141). pNCC was more abundant in the urinary exosomes in the high lateralization index (hLI, > = 4) group (1.64 folds, P = 0.0080) than in the low LI (lLI, < 4) group (Figure 1). Carriers of the somatic KCNJ5 mutations, compared with non-carriers, had more abundant pNCC expression in urinary exosomes (1.99 folds, P = 0.0399) (Figure 2). Conclusions: The expression of pNCC in urinary exosomes in patients with PA with various subtypes and genotypes was different. They can be used as biomarkers of AVS for PA subtyping.