期刊
CLINICAL ENDOCRINOLOGY
卷 90, 期 1, 页码 241-249出版社
WILEY
DOI: 10.1111/cen.13889
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资金
- Arthritis Research UK [20843]
- JABBS Foundation (Birmingham, United Kingdom)
- Queen Elizabeth Hospital Birmingham Charity
- National Institute for Health Research UK
- Wellcome Trust [105479/Z/14/Z]
- Wellcome Trust [105479/Z/14/Z] Funding Source: Wellcome Trust
Objective Patients with chronic kidney disease (CKD) have dysregulated cortisol metabolism secondary to changes in 11 beta-hydroxysteroid dehydrogenase (11 beta-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 11 beta-HSD was measured as the metabolite ratio (tetrahydrocortisol [THF]+5 alpha-tetrahydrocortisol [5 alpha THF])/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 m(2) and median urine albumin-creatinine ratio of 35.5 mg/mmol. (THF+5 alpha THF)/THE correlated negatively with eGFR (Spearman's rho = -0.116, P = 0.032) and positively with C-reactive protein (rho = 0.208, P < 0.001). In multivariable analysis, C-reactive protein remained a significant independent predictor of (THF+5 alpha THF)/THE, but eGFR did not. Elevated (THF+5 alpha THF)/THE was associated with HbA1c (rho = 0.144, P = 0.008) and diabetes mellitus (odds ratio for high vs low tertile of (THF+5 alpha THF)/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 11 beta-HSD in our cohort comprising a spectrum of renal function was associated with inflammation and impaired glucose control.
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