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- Title
Glucocorticoid activation by 11β‐hydroxysteroid dehydrogenase enzymes in relation to inflammation and glycaemic control in chronic kidney disease: A cross‐sectional study.
- Authors
Sagmeister, Michael S.; Taylor, Angela E.; Fenton, Anthony; Wall, Nadezhda A.; Chanouzas, Dimitrios; Nightingale, Peter G.; Ferro, Charles J.; Arlt, Wiebke; Cockwell, Paul; Hardy, Rowan S.; Harper, Lorraine
- Abstract
Summary: 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.
- Subjects
GLUCOCORTICOIDS; PREDNISOLONE; HYDROXYSTEROID dehydrogenases; ALCOHOL dehydrogenase; INFLAMMATION; CHRONIC kidney failure
- Publication
Clinical Endocrinology, 2019, Vol 90, Issue 1, p241
- ISSN
0300-0664
- Publication type
Article
- DOI
10.1111/cen.13889