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

Vista sencilla de ítem
dc.contributor.authorUslar, Thomas
dc.contributor.authorNewman, Andrew J.
dc.contributor.authorTapia-Castillo, Alejandra
dc.contributor.authorCarvajal, Cristian A.
dc.contributor.authorFardella, Carlos E.
dc.contributor.authorAllende, Fidel
dc.contributor.authorSolari, Sandra
dc.contributor.authorTsai, Laura C.
dc.contributor.authorMilks, Julia
dc.contributor.authorCherney, Michael
dc.contributor.authorStouffer, David G.
dc.contributor.authorAuchus, Richard
dc.contributor.authorBrown, Jenifer M.
dc.contributor.authorBaudrand, René
dc.contributor.authorVaidya, Anand
dc.coverage.spatialUSA
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.isoen
dc.publisherEndocrine Society
dc.relation.ispartofseriesUSA
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subject11β-hydroxysteroid dehydrogenase type 2
dc.subjectCortisol
dc.subjectCortisone
dc.subjectChronic kidney disease
dc.subjectMineralcorticoid receptor activation
dc.titleProgressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines
dc.typeArticle
dcterms.accessRightsCon embargo
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