Kings County Hospital and State University of New York Downstate Medical Center, 450 Clarkson Avenue, Box 49, Brooklyn, New York 11203, USA.
J Clin Endocrinol Metab. 2012 Oct;97(10):3622-9. doi: 10.1210/jc.2012-1411. Epub 2012 Aug 7.
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.
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.
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.
DESIGN/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.
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.
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.
矿皮质激素受体可通过存在于肾脏中的 11β-羟甾类脱氢酶 2 将活性皮质醇转化为非活性皮质酮，从而避免皮质醇过量。皮质醇和皮质酮的代谢物分别以四氢皮质醇（5αTHF+5βTHF）和四氢皮质酮（THE）的形式排泄在尿液中。
患有慢性肾病（CKD）和特发性高血压的患者，其将皮质醇转化为皮质酮的能力存在功能缺陷，从而导致矿皮质激素受体被激活。
本研究旨在研究 CKD、肾移植后和特发性高血压患者尿液类固醇（5αTHF+5βTHF）与 THE 的比值，并将其与对照组进行比较。
我们纳入了 44 名患者（17 名 CKD 患者、8 名肾移植后患者、19 名特发性高血压患者）和 12 名对照者。我们采用气相色谱/质谱法测定了患者和对照组的 5α-THF、5β-THF、THE、游离活性皮质醇和非活性皮质酮的点尿样。我们收集了年龄、性别、肾脏疾病病因、身高、体重、体重指数、血压、血清电解质、醛固酮和血浆肾素活性等数据。计算了血压百分位数和 z 分数。使用改良 Schwartz 公式计算肾小球滤过率。
与特发性高血压组（平均值±标准差（SDS）=0.59±0.23；P=0.02）和对照组（平均值±SDS=0.52±0.25；P=0.01）相比，CKD 患者的 5αTHF+5βTHF 与 THE 的比值明显更高（平均值±SDS=1.31±1.07）。肾移植后组的比值无明显差异（平均值±SDS=0.71±0.55）。高血压和 CKD 组的尿游离皮质醇与游离皮质酮比值明显高于对照组。5αTHF+5βTHF 与 THE 的比值与肾小球滤过率呈负相关，与收缩压和舒张压 z 分数呈正相关。CKD 组的血压 z 分数与比值的相关性强于特发性高血压和肾移植后组。
我们已经阐明了儿童 CKD 和特发性高血压患者 11β-羟甾类脱氢酶 2 的功能缺陷。通过气相色谱/质谱法对尿液中的 5α-THF、5β-THF 和 THE 进行分析，应该成为 CKD 和高血压患者常规检查的一部分。
