Role of 11βHSD Type 2 Enzyme Activity in Essential Hypertension and Children with Chronic Kidney Disease (CKD)

Mongia, Anil; Vecker, Risa; George, Minu; Pandey, Anita; Tawadrous, Hanan; Schoeneman, Morris J.; Muneyyirci-Delale, Ozgul; Nacharaju, Vijaya L.; Ten, Svetlana; Bhangoo, Amrit

doi:10.1210/jc.2012-1411

Cited by 24 publications

(19 citation statements)

References 49 publications

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“…These pathogenesis might be involved in kidney diseases in chronic hypercortisolemic states [7,20]. A functional defect in the ability to convert cortisol to cortisone existed in patients with essential hypertension and chronic kidney diseases (CKD), which would result in the activation of mineralocorticoid receptor [21]. MR antagonists not only improve the prognosis for patients with cardiovascular diseases, but also been used in patients with CKD due to its potential effects on reducing proteinuria and kidney damage [22][23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Association Between Serum Cortisol and Chronic Kidney Disease in Patients with Essential Hypertension

Xiang²,

Hu³

et al. 2016

Kidney Blood Press Res

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Background/Aims: Serum cortisol level is elevated in patients with essential hypertension. We aimed at investigating the association of serum cortisol levels with parameters of renal function in essential hypertension. Methods: One hundred and seventy-eight patients with essential hypertension participated in the study. Fasting serum samples were collected at 8:00 am. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine- cystatin C equation (eGFRcr-cys). Correlation analysis and stepwise regression analysis were used to detect the relationship between cortisol and eGFRcr-cys. The distributions of serum cortisol were split by the tertiles and subjects were stratified into those with low, median and high levels accordingly. Results: Serum cortisol levels were significantly higher in subjects whose eGFRcr-cys<90 ml/min/1.73 m² than subjects whose eGFRcr-cys>90 ml/min/1.73 m² (394.0±93.4 vs. 343.2±98.4 nmol/L, P=0.001). Age, systolic blood pressure, and serum total cholesterol, uric acid, cortisol levels were significantly associated with eGFRcr-cys, serum levels of creatinine and cystatin C. After adjusting for clinical factors, serum cortisol level had a statistically significant negative association with the eGFRcr-cys (β=-0.19, P=0.027), and positive associations with cystatin C (β=0.31, P=0.001) and creatinine (β=0.14, P=0.044). With the increment of cortisol tertile, the eGFRcr-cys significantly decreased (93.18±14.36 vs. 84.61±14.67 vs. 81.29±12.36 ml/min/1.73 m² for low, median and high tertile, respecively, P=0.001). Conclusion: Serum cortisol level was negatively correlated with eGFRcr-cys in subjects with essential hypertension. Further studies are needed to investigate whether cortisol plays a role in hypertensive nephropathy development.

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Section: Discussionmentioning

confidence: 99%

Association Between Serum Cortisol and Chronic Kidney Disease in Patients with Essential Hypertension

Xiang²,

Hu³

et al. 2016

Kidney Blood Press Res

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“…Family studies have shown that 20- 40% of cases seen are genetically determined. Different monogenic causes of PH have been established including mutations in the corticosteroidogenic genes, CYP11B1, and HSD11B2 28-30 , mutations in the epithelial sodium channel (SCNN1B, SCNN1G), in the WNK serinethreonine kinase, 31,32 and polymorphisms in the renin-angiotensin-aldosterone system (RAAS) 30,33,34 . However, pure monogenic causes of PH are still rare.…”

Section: Risk Factors For Essential Hypertensionmentioning

confidence: 99%

Hypertension in the Teenager

Anyaegbu

Dharnidharka

2014

Pediatric Clinics of North America

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“…5 Furthermore, we examined whether augmented GC activation in CKD relates to impaired glucose handling.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have described a correlation between loss of renal function and GC activation by 11β-HSD enzymes, measured as a rise in the ratio of cortisol/cortisone or a rise in the ratio of their respective metabolites (tetrahydrocortisol [THF]+5α-tetrahydrocortisol [5αTHF])/ tetrahydrocortisone (THE). 4,5 Due to limitations of measuring steroid metabolism in this way, the relative contribution of each 11β-HSD enzyme to the reported shift in cortisol metabolism is not known. Loss of renal expression of 11β-HSD2 and diminished cortisol inactivation likely plays a role.…”

Section: Introductionmentioning

confidence: 99%

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

Sagmeister

Taylor

Fenton

et al. 2018

Clinical Endocrinology

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SummaryObjectivePatients 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.MethodsWe 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.ResultsThe 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.ConclusionsIn summary, glucocorticoid activation by 11β‐HSD in our cohort comprising a spectrum of renal function was associated with inflammation and impaired glucose control.

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Role of 11βHSD Type 2 Enzyme Activity in Essential Hypertension and Children with Chronic Kidney Disease (CKD)

Cited by 24 publications

References 49 publications

Association Between Serum Cortisol and Chronic Kidney Disease in Patients with Essential Hypertension

Association Between Serum Cortisol and Chronic Kidney Disease in Patients with Essential Hypertension

Hypertension in the Teenager

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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