Glucocorticoid activation by 11β-hydroxysteroid dehydrogenase enzymes in relation to inflammation and glycaemic control in chronic kidney disease: A cross-sectional study

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  • Anthony Fenton
  • Peter Nightingale
  • Charles J Ferro
  • Paul Cockwell
  • Rowan Hardy
  • Lorraine Harper


Objective Patients with chronic kidney disease (CKD) have dysregulated cortisol metabolism secondary to changes in 11β‐hydroxysteroid dehydrogenase (11β‐HSD) enzymes. The determinants of this and its clinical implications are poorly defined. Methods We performed a cross‐sectional study to characterize shifts in cortisol metabolism in relation to renal function, inflammation and glycaemic control. Systemic activation of cortisol by 11β‐HSD was measured as the metabolite ratio (tetrahydrocortisol [THF]+5α‐tetrahydrocortisol [5αTHF])/tetrahydrocortisone (THE) in urine. Results The cohort included 342 participants with a median age of 63 years, median estimated glomerular filtration rate (eGFR) of 28 mL/min/1.73 m2 and median urine albumin‐creatinine ratio of 35.5 mg/mmol. (THF+5αTHF)/THE correlated negatively with eGFR (Spearman's ρ = −0.116, P = 0.032) and positively with C‐reactive protein (ρ = 0.208, P < 0.001). In multivariable analysis, C‐reactive protein remained a significant independent predictor of (THF+5αTHF)/THE, but eGFR did not. Elevated (THF+5αTHF)/THE was associated with HbA1c (ρ = 0.144, P = 0.008) and diabetes mellitus (odds ratio for high vs low tertile of (THF+5αTHF)/THE 2.57, 95% confidence interval 1.47‐4.47). Associations with diabetes mellitus and with HbA1c among the diabetic subgroup were independent of eGFR, C‐reactive protein, age, sex and ethnicity. Conclusions In summary, glucocorticoid activation by 11β‐HSD in our cohort comprising a spectrum of renal function was associated with inflammation and impaired glucose control.

Bibliographic note

© 2018 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.


Original languageEnglish
Pages (from-to)241-249
Number of pages9
JournalClinical Endocrinology
Issue number1
Early online date25 Oct 2018
Publication statusPublished - Jan 2019