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Clinical, biochemical, and miRNA profile of subjects with positive screening of primary aldosteronism and nonclassic apparent mineralocorticoid excess

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Abstract

Primary aldosteronism (PA) and nonclassic apparent mineralocorticoid excess (NCAME) have been recognized as endocrine-related conditions having a broad clinical-biochemical spectrum, spanning from normotension to severe arterial hypertension (AHT). However, the coexistence of both phenotypes have not been reported to date.

Aim

To identify and characterize clinical and biochemical parameters of subjects with both PA and NCAME conditions (NCAME&PA) and study the miRNA cargo in their urinary extracellular vesicles as potential biomarkers for this novel condition.

Methods

We performed a cross-sectional study of 206 Chilean adult subjects from a primary care cohort. We measured blood pressure (BP), cortisol (F), cortisone (E), aldosterone, plasma renin activity (PRA), microalbuminuria (MAC), plasma NGAL, MMP9, fractional-potassium-excretion (FEK). Subjects were classified as NCAME&PA, PA, NCAME, essential hypertensives (EH), or healthy controls (CTL). EV-miRNAs were quantified by Taqman-qPCR.

Results

We found that 30.6% subjects had an abnormal endocrine phenotype: NCAME&PA (6.8%), PA (11.2%) or NCAME (12.6%), and the prevalence of AHT was 92.9%, 82.6%, and 65%, respectively. NCAME&PA subjects had both lower cortisone (p < 0.05) and lower PRA (p < 0.0001), higher FEK (p = 0.02) and higher MAC (p = 0.01) than EH or CTL. NCAME&PA subjects had also higher NGAL levels than CTL and PA (p < 0.05). Exosome miR-192, miR-133a and miR-21 expression decreased with phenotype severity and correlated with BP and PRA (p < 0.05).

Conclusion

We identified adult subjects with a combined condition of NCAME and PA associated with higher BP, increased renal and endothelial damage markers than control and EH. Additionally, we observed a differential expression of a specific miRNAs, suggesting a potential role of these miRNAs associated to this novel combined phenotype.

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Acknowledgements

We acknowledge to all the patients and researchers who supported studies associated with this paper.

Funding

This study was supported by the following grants: ANID-CONICYT FONDECYT 1212006; FONDECYT POSTDOCTORAL 3200646; CONICYT-FONDEQUIP EQM150023; ANID—Millennium Science Initiative Program- IMII P09/016-F, ICN09_016; CORFO BMRC-13CTI-21526-P1; SOCHED 2019-09 and CETREN-UC.

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  1. These authors contributed equally: Alejandra Tapia-Castillo, Cristian A. Carvajal

Authors and Affiliations

  1. Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

    Alejandra Tapia-Castillo, Cristian A. Carvajal, Jorge A. Pérez & Carlos E. Fardella

  2. Millennium Institute on Immunology and Immunotherapy (IMII-ICM), Santiago, Chile

    Alejandra Tapia-Castillo, Cristian A. Carvajal, Jorge A. Pérez & Carlos E. Fardella

  3. Centro Traslacional de Endocrinología UC (CETREN-UC), Pontificia Universidad Católica de Chile, Santiago, Chile

    Alejandra Tapia-Castillo, Cristian A. Carvajal, Jorge A. Pérez & Carlos E. Fardella

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Tapia-Castillo, A., Carvajal, C.A., Pérez, J.A. et al. Clinical, biochemical, and miRNA profile of subjects with positive screening of primary aldosteronism and nonclassic apparent mineralocorticoid excess. Endocrine 77, 380–391 (2022). https://doi.org/10.1007/s12020-022-03103-x

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