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We hypothesized that relative 11\u03b2HSD2 insufficiency manifests across a wide spectrum of progressively declining kidney function, including within the normal range.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u03b2HSD2 activity. A validation cohort (n = 101) enrolled only individuals with normal kidney function (eGFR \u2265 60\u2005mL\/min\/1.73\u2005m2) in whom 11\u03b2HSD2 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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the discovery cohort, lower eGFR was associated with higher F\/E (P-trend &amp;lt; .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 &amp;lt; .01), which persisted following DST (P-trend &amp;lt; .001) and ACTHstim (P-trend &amp;lt; .05). The fractional excretion of potassium, a marker of renal MR activity, was higher with higher F\/E (P-trend &amp;lt; .01) and with lower eGFR (P-trend &amp;lt; .0001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A continuum of declining 11\u03b2HSD2 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgae663","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T15:21:54Z","timestamp":1726845714000},"page":"1037-1043","source":"Crossref","is-referenced-by-count":17,"title":["Progressive 11\u03b2-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-855X","authenticated-orcid":false,"given":"Thomas","family":"Uslar","sequence":"first","affiliation":[{"name":"Department of Endocrinology, CETREN-UC, Red Salud UC-CHRISTUS, Pontificia Universidad Cat\u00f3lica de Chile , Santiago 8330077 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