Progressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines
Authors' 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.
Study context
- Population
- Adults across a spectrum of kidney function, from normal estimated glomerular filtration rate (eGFR) to chronic kidney disease (CKD) stage 5, recruited at 2 academic centers
- Participants
- 500 vs 101
- Exposure
- Discovery vs Validation
- Discoveryn = 500
- Validationn = 101
- Outcome
- 11βHSD2 activity (serum F/E) vs eGFR
Methodological details2 academic centers, discovery and validation cohorts
- 2 academic centers
- Discovery and validation cohorts
Main finding
As reported in the abstract
- Discovery cohort: lower eGFR associated with higher F/E
- P-trend < .001
- Validation cohort (normal eGFR): inverse association between eGFR and both F/E and 11OH/K ratios
- P-trend < .01
- Validation cohort: association persisted after dexamethasone suppression test (DST)
- P-trend < .001
- Validation cohort: association persisted after ACTHstim
- P-trend < .05
Observational data: associations, not effects.
Further findings
Fractional excretion of potassium (marker of renal mineralocorticoid receptor (MR) activity)
- Higher with higher F/E
- P for trend < 0.01
- Higher with lower eGFR
- P for trend < 0.0001
Original publication
Progressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines. J Clin Endocrinol Metab. Published 23 September 2024. doi:10.
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