Progressive 11β-hydroxysteroid dehydrogenase type 2 insufficiency as kidney function declines

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dc.catalogadorvdr
dc.contributor.authorUslar N., Thomas
dc.contributor.authorNewman, Andrew J.
dc.contributor.authorTapia Castillo, Alejandra
dc.contributor.authorCarvajal Maldonado, Cristián Andrés
dc.contributor.authorFardella B., Carlos
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 Biggs, René
dc.contributor.authorVaidya, Anand
dc.date.accessioned2024-11-21T18:22:59Z
dc.date.available2024-11-21T18:22:59Z
dc.date.issued2024
dc.description.abstractBackground It has been postulated that chronic kidney disease (CKD) is a state of relative 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) insufficiency, resulting in increased cortisol-mediated mineralocorticoid receptor (MR) activation. We hypothesized that relative 11 beta HSD2 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 11 beta HSD2 activity. A validation cohort (n = 101) enrolled only individuals with normal kidney function (eGFR >= 60 mL/min/1.73 m(2)) in whom 11 beta HSD2 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 11 beta HSD2 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.format.extent7 páginas
dc.fuente.origenWOS
dc.fuente.origenORCID
dc.identifier.doi10.1210/clinem/dgae663
dc.identifier.eissn1945-7197
dc.identifier.issn0021-972X
dc.identifier.urihttps://doi.org/10.1210/clinem/dgae663
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/88635
dc.identifier.wosidWOS:001330950900001
dc.information.autorucEscuela de Medicina; Uslar N., Thomas; 0000-0001-7213-855X; 187161
dc.information.autorucEscuela de Medicina; Tapia Castillo, Alejandra; 0000-0002-6081-1468; 1012854
dc.information.autorucEscuela de Medicina; Carvajal Maldonado, Cristián Andrés; 0000-0002-0668-412X; 8586
dc.information.autorucEscuela de Medicina; Fardella B., Carlos; 0000-0002-5500-4434; 66235
dc.information.autorucEscuela de Medicina; Allende, Fidel; 0000-0002-6508-4052; 1004550
dc.information.autorucEscuela de Medicina; Solari, Sandra; 0000-0002-3185-4717; 1871
dc.information.autorucEscuela de Medicina; Baudrand Biggs, René; 0000-0002-8655-4957; 1024
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final7
dc.pagina.inicio1
dc.revistaJournal of Clinical Endocrinology & Metabolism
dc.rightsacceso restringido
dc.rightsacceso restringido
dc.subject11 beta-hydroxysteroid dehydrogenase type 2
dc.subjectCortisol
dc.subjectCortisone
dc.subjectChronic kidney disease
dc.subjectMineralocorticoid receptor activation
dc.subject.ddc610
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleProgressive 11β-hydroxysteroid dehydrogenase type 2 insufficiency as kidney function declines
dc.typeartículo
dc.volumen00
sipa.codpersvinculados187161
sipa.codpersvinculados1012854
sipa.codpersvinculados8586
sipa.codpersvinculados66235
sipa.codpersvinculados1004550
sipa.codpersvinculados1871
sipa.codpersvinculados1024
sipa.trazabilidadWOS;2024-10-19
sipa.trazabilidadORCID;2024-11-18
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