title: Role of 11βHSD type 2 enzyme activity in essential hypertension and children with chronic kidney disease (CKD).
abstract: BACKGROUND
  The mineralocorticoid receptor is protected from excess of glucocorticoids by conversion of active cortisol to inactive cortisone by enzyme 11β-hydroxysteroid dehydrogenase type 2 present in the kidney. The metabolites of cortisol and cortisone are excreted in the urine as tetrahydrocortisol (5αTHF+5βTHF) and tetrahydrocortisone (THE), respectively.
  
  
  OBJECTIVE
  Patients with chronic kidney disease (CKD) and essential hypertension have a functional defect in their ability to convert cortisol to cortisone, thus leading to the activation of mineralocorticoid receptor.
  
  
  OBJECTIVE
  The objective of the investigation was to study the ratio of urinary steroids (5αTHF+5βTHF) to THE in patients with CKD, postrenal transplant, and essential hypertension and to compare the ratio with controls.
  
  
  METHODS
  We enrolled 44 patients (17 with CKD, eight postrenal transplant, 19 with essential hypertension) and 12 controls. We measured spot urinary 5α-THF, 5β-THF, THE, free active cortisol and inactive cortisone by gas chromatography/mass spectrometry. We collected data on age, sex, cause of kidney disease, height, weight, body mass index, blood pressure, serum electrolytes, aldosterone, and plasma renin activity. Blood pressure percentiles and z-scores were calculated. The glomerular filtration rate was calculated using the modified Schwartz formula.
  
  
  RESULTS
  The ratios of 5αTHF+5βTHF to THE were significantly higher in patients with CKD [mean±sd score (SDS)=1.31±1.07] as compared with essential hypertension (mean±SDS=0.59±0.23; P=0.02) and controls (mean±SDS=0.52±0.25; P=0.01). In the postrenal transplant group, the ratio was not significantly different (mean±SDS=0.71±0.55). The urinary free cortisol to free cortisone ratios were significantly higher in the hypertension and CKD groups as compared with the controls. The 5αTHF+5βTHF to THE ratio negatively correlated with the glomerular filtration rate and positively correlated with systolic and diastolic blood pressure z-scores. The correlation of the blood pressure z-scores with ratios was stronger in the CKD group than the essential hypertension and posttransplant groups.
  
  
  CONCLUSIONS
  We have elucidated a functional deficiency of 11β-hydroxysteroid dehydrogenase type 2 in children with CKD and a subset of essential hypertension. Urinary 5α-THF, 5β-THF, and THE analysis by gas chromatography/mass spectrometry should be a part of routine work-up of CKD and hypertensive patients.
authors.affiliation: Kings County Hospital and State University of New York Downstate Medical Center, 450 Clarkson Avenue, Box 49, Brooklyn, New York 11203, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Mongia
authors.forename: Risa
authors.initials: R
authors.lastname: Vecker
authors.forename: Minu
authors.initials: M
authors.lastname: George
authors.forename: Anita
authors.initials: A
authors.lastname: Pandey
authors.forename: Hanan
authors.initials: H
authors.lastname: Tawadrous
authors.forename: Morris
authors.initials: M
authors.lastname: Schoeneman
authors.forename: Ozgul
authors.initials: O
authors.lastname: Muneyyirci-Delale
authors.forename: Vijaya
authors.initials: V
authors.lastname: Nacharaju
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ten
authors.forename: Amrit
authors.initials: A
authors.lastname: Bhangoo
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006977:Hypertension, Renal / Q000378:metabolism* / Q000601:surgery; D007223:Infant; D016030:Kidney Transplantation; D008297:Male; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000601:surgery; D013760:Tetrahydrocortisol / Q000031:analogs & derivatives / Q000652:urine; D013761:Tetrahydrocortisone / Q000652:urine; D055815:Young Adult
chemical_list: D018161:Receptors, Mineralocorticoid; C006461:allotetrahydrocortisol; D013761:Tetrahydrocortisone; D013760:Tetrahydrocortisol; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D006854:Hydrocortisone