Glucocorticoid activation by 11β-hydroxysteroid dehydrogenase enzymes in relation to inflammation and glycaemic control in chronic kidney disease: a cross-sectional study
Author(s)
Type
Journal Article
Abstract
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.
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.
Date Issued
2019-01-01
Date Acceptance
2018-10-22
Citation
Clinical Endocrinology, 2019, 90 (1), pp.241-249
ISSN
0300-0664
Publisher
Wiley
Start Page
241
End Page
249
Journal / Book Title
Clinical Endocrinology
Volume
90
Issue
1
Copyright Statement
© 2018 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30358903
Subjects
11-BETA-HSD1
DIABETES-MELLITUS
Endocrinology & Metabolism
EXPRESSION
HYPERGLYCEMIA
INSULIN-RESISTANCE
Life Sciences & Biomedicine
METABOLISM
MORTALITY
OBESITY
Science & Technology
TYPE-1 INHIBITOR
URINARY CORTISOL
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2018-12-18