Progressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines

Vista sencilla de ítem
dc.contributor.authorUslar, Thomas
dc.coverage.spatialEstados Unidos
dc.date.accessioned2026-02-24T18:15:05Z
dc.date.available2026-02-24T18:15:05Z
dc.date.issued2024-09
dc.description.abstractBackground: It has been postulated that chronic kidney disease (CKD) is a state of relative 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) insufficiency, resulting in increased cortisol-mediated mineralocorticoid receptor (MR) activation. We hypothesized that relative 11βHSD2 insufficiency manifests across a wide spectrum of progressively declining kidney function, including within the normal range. Methods: Adult participants were recruited at 2 academic centers. A discovery cohort (n = 500) enrolled individuals with estimated glomerular filtration rate (eGFR) ranging from normal to CKD stage 5, in whom serum cortisol-to-cortisone (F/E) was measured as a biomarker of 11βHSD2 activity. A validation cohort (n = 101) enrolled only individuals with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2) in whom 11βHSD2 activity was assessed via serum F/E and 11-hydroxy-to-11-keto androgen (11OH/K) ratios following multiple maneuvers: oral sodium suppression test, dexamethasone suppression test (DST), and ACTH-stimulation test (ACTHstim). Results: In the discovery cohort, lower eGFR was associated with higher F/E (P-trend < .001). Similarly, in the validation cohort, with normal eGFR, an inverse association between eGFR and both F/E and 11OH/K ratios was observed (P-trend < .01), which persisted following DST (P-trend < .001) and ACTHstim (P-trend < .05). The fractional excretion of potassium, a marker of renal MR activity, was higher with higher F/E (P-trend < .01) and with lower eGFR (P-trend < .0001). Conclusion: A continuum of declining 11βHSD2 activity was observed with progressively lower eGFR in individuals spanning a wide spectrum of kidney function, including those with apparently normal kidney function. These findings implicate cortisol-mediated MR activation in the pathophysiology of hypertension and cardiovascular disease in CKD.
dc.identifier.citationThe Journal of Clinical Endocrinology & Metabolism, Vol. 110, N° 4 (2025) p. 1037–1043
dc.identifier.doihttps://doi.org/10.1210/clinem/dgae663
dc.identifier.issn0021972X
dc.identifier.orcidhttps://orcid.org/0000-0002-6081-1468
dc.identifier.urihttps://hdl.handle.net/20.500.12254/7465
dc.language.isoeng
dc.publisherEndocrine Society
dc.relation.ispartofseriesUSA
dc.rightsAcceso abierto
dc.rights.licenseAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subject11β-Hydroxysteroid Dehydrogenase Type 2
dc.subject.nabs07 - Protección y mejora de la salud humana
dc.subject.odsODS 3 - Salud y bienestar
dc.subject.oecd3.2.28 - Otros Temas de Medicina Clínica
dc.subject.techBM - Tecnologías Biomédicas
dc.titleProgressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines
dc.typeArticle
dc.type.coarhttp://purl.org/coar/resource_type/c_6501
Archivos
Bloque original
Mostrando 1 - 1 de 1
No hay miniatura disponible
Nombre:
2025_Progressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines.pdf
Tamaño:
755.57 KB
Formato:
Adobe Portable Document Format
Descargar
Bloque de licencias
Mostrando 1 - 1 de 1
No hay miniatura disponible
Nombre:
license.txt
Tamaño:
347 B
Formato:
Item-specific license agreed upon to submission
Descripción:
Descargar
Colecciones
Artículos de Revistas