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

2012 ◽  
Vol 97 (10) ◽  
pp. 3622-3629 ◽  
Author(s):  
Anil Mongia ◽  
Risa Vecker ◽  
Minu George ◽  
Anita Pandey ◽  
Hanan Tawadrous ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Blood Pressure ◽  
Essential Hypertension ◽  
Kidney Disease ◽  
Mineralocorticoid Receptor ◽  
Filtration Rate ◽  
Hydroxysteroid Dehydrogenase ◽  
Gas Chromatography Mass Spectrometry ◽  
Z Scores

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. Hypothesis: 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. 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. 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.

scholarly journals Uninephrectomy reduces 11β-hydroxysteroid dehydrogenase type 1 and type 2 concomitantly with an increase in blood pressure in rats

2012 ◽  
Vol 214 (3) ◽  
pp. 373-380 ◽  
Author(s):  
M Lauterburg ◽  
G Escher ◽  
B Dick ◽  
D Ackermann ◽  
F J Frey
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Hydroxysteroid Dehydrogenase ◽  
Gas Chromatography Mass Spectrometry ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Arterial Blood

Renal allograft donors are at risk of developing hypertension. Here, we hypothesized that this risk is at least in part explained by an enhanced intracellular availability of 11β-hydroxyglucocorticoids due to an increased 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), an intracellular prereceptor activator of biologically inactive 11-ketocorticosteroids in the liver, and/or a diminished 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an inactivator of 11β-hydroxyglucocorticoids in the kidney. To test this hypothesis, uninephrectomized (UNX) (n=9) and sham-operated (n=10) adult Sprague–Dawley rats were investigated. Mean arterial blood pressure and heart rate were measured continuously by telemetry for 6 days in week 5 after UNX. The mRNA of11β-Hsd1and11β-Hsd2in liver and kidney tissues were assessed by RT-PCR and the 11β-HSD activities were directly quantified in their corresponding tissues by determining the ratios of (tetrahydrocorticosterone+5α-tetrahydrocorticosterone)/tetrahydrodehydrocorticosterone ((THB+5α-THB)/THA) and of corticosterone/dehydrocorticosterone (B/A) by gas chromatography–mass spectrometry. The apparent total body activities of 11β-HSD1 and 11β-HSD2 were estimated using the urinary and plasma ratios of (THB+5α-THB)/THA and B/A. Mean arterial blood pressure was increased after UNX when compared with sham operation. Hepatic mRNA content of11β-Hsd1and hepatic, plasma, and urinary ratios of (THB+5α-THB)/THA were decreased after UNX, indicating diminished access of glucocorticoids to its receptors. In renal tissue,11β-Hsd2mRNA was reduced and B/A ratios measured in kidney, plasma, and urine were increased, indicating reduced 11β-HSD2 activity and enhanced access of glucocorticoids to mineralocorticoid receptors. Both 11β-HSD1 and 11β-HSD2 are downregulated after UNX in rats, a constellation considered to induce hypertension.

MO640LASER DOPPLER FLOWMETRY IN STUDYING OF MICROVASCULAR DISORDERS IN PATIENTS WITH DIABETIC NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Petr Vasilev ◽  
Alexander Shishkin ◽  
Nikolai Erofeev ◽  
Mikhail Erman ◽  
Ivan Pchelin
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Type 2 Diabetes Mellitus ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Doppler Flowmetry

Abstract Background and Aims According to various research, vascular complications of type 2 diabetes mellitus are the main reason for patients' mortality. The most specific one, observed in patients with diabetes only, is diabetic microangiopathy, especially diabetic nephropathy. This complication accounts for more than 20% of cases of chronic kidney disease. So, the development of non-invasive methods for the diagnosis of vascular complications of type 2 diabetes mellitus is critically important. There is a perspective method for this problem - Laser Doppler flowmetry (LDF). It is currently used in the diagnosis of diabetic microangiopathy, but the limiting factor is the lack of a unified algorithmic approach to the data interpretation. This work aimed to analyze changes in the amplitude indicators of the low-frequency part of the LDF signal spectrum in patients with chronic kidney disease and type 2 diabetes and to identify their correlations with the glomerular filtration rate. Method The study included 42 patients (20 men and 22 women) with type 2 diabetes mellitus chronic kidney disease (stage C3-C4). The age of patients was 58-77 years (66 years on average). The duration of diabetes was more than 5 years (on average 7 years). All patients had diabetic nephropathy with a decrease in glomerular filtration rate, chronic kidney disease stage C3-C4. Laser Doppler flowmetry was done using the "LAZMA MC-1" system ("Lazma", Russia). Each patient had a 10-minute LDF registration. The sensor was placed on the skin of the rear of the foot. After recording the LDF curve, the special software has calculated amplitudes of endothelial, myogenic, neurogenic, respiratory, and pulse flux motions. Then we assessed the amplitude contribution of every frequency range to the total power of the local flux motion region. The next step was a correlation analysis with the estimated glomerular filtration rate. For statistical analysis, we used the GraphPad Prism 8 (GraphPad Software, USA). Results All examined patients had amplitude peaks in the neurogenic, myogenic, respiratory, and pulse ranges. There were no significant correlations between the glomerular filtration rate and the amplitudes of myogenic and neurogenic flux motions (p>0.05) (Fig. 1). However, there was a significant positive correlation between the contribution of myogenic flux motions to the low-frequency range and glomerular filtration rate (p<0.01), and a negative one – for the contribution of neurogenic flux motions (p<0.01) (Fig. 2). In six observations there was a tendency to a decrease in the contribution of endothelial flux motions as the glomerular filtration rate decreased. Conclusion The results of this study showed that laser Doppler flowmetry has the potential to diagnosis the nature of the dysfunction of individual microcirculation modulation mechanisms. In patients with chronic kidney disease of the C3-C4 stage decreasing the glomerular filtration rate correlated with decreasing the contribution of myogenic flux motions and increasing the contribution of neurogenic flux motions to the total power of the low-frequency part of the LDF signal amplitude-frequency spectrum. These changes can be explained within the framework of the existing understanding of the pathogenesis of diabetic microangiopathy, namely, damage to the smooth muscle layer of the wall of arterioles and venules with damage to myocyte pacemakers and changes of basal vascular tone pattern. It causes an increase in the role of neurogenic modulation of the micro-vascular bloodstream. These data can be an additional argument in favor of the further development of improving laser Doppler flowmetry using for the tasks of early (preclinical) non-invasive diagnosis of microvascular disorders in patients with type 2 diabetes mellitus, as well as for monitoring the effectiveness of the therapy. The reported study was funded by RFBR, project number 19-315-90080.

Evolution of glomerular filtration rate in patients with essential hypertension: impact of type 2 diabetes

2014 ◽  
Vol 8 (4) ◽  
pp. e101
Author(s):  
Julian Segura ◽  
Cesar Cerezo ◽  
Enrique Morales ◽  
Luisa Fernandez ◽  
Lucia Guerrero ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glomerular Filtration Rate ◽  
Essential Hypertension ◽  
Glomerular Filtration ◽  
Filtration Rate

scholarly journals Association Between Classical and Emerging Risk Factors for Diabetic Kidney Disease and Albuminuria in a Cohort of Type 2 Diabetes Mellitus Patients

2021 ◽  
Vol 18 (3) ◽  
pp. 17-25
Author(s):  
Stoiţă Marcel ◽  
Popa Amorin Remus
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Significant Positive Association ◽  
Diabetic Kidney

Abstract The presence of albuminuria in patients with type 2 diabetes mellitus is a marker of endothelial dysfunction and also one of the criteria for diagnosing diabetic kidney disease. The present study aimed to identify associations between cardiovascular risk factors and renal albumin excretion in a group of 218 patients with type 2 diabetes mellitus. HbA1c values, systolic blood pressure, diastolic blood pressure were statistically significantly higher in patients with microalbuinuria or macroalbuminuria compared to patients with normoalbuminuria (p <0.01). We identified a statistically significant positive association between uric acid values and albuminuria, respectively 25- (OH)2 vitamin D3 deficiency and microalbuminuria (p <0.01).

Variability in HbA1c, blood pressure, lipid parameters and serum uric acid, and risk of development of chronic kidney disease in type 2 diabetes

2017 ◽  
Vol 19 (11) ◽  
pp. 1570-1578 ◽  
Author(s):  
Antonio Ceriello ◽  
Salvatore De Cosmo ◽  
Maria Chiara Rossi ◽  
Giuseppe Lucisano ◽  
Stefano Genovese ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
Lipid Parameters

scholarly journals Increased blood pressure, aldosterone activity, and regional differences in renal ENaC protein during vasopressin escape

2004 ◽  
Vol 287 (5) ◽  
pp. F1076-F1083 ◽  
Author(s):  
Jian Song ◽  
Xinqun Hu ◽  
Osman Khan ◽  
Ying Tian ◽  
Joseph G. Verbalis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Regional Differences ◽  
Water Retention ◽  
Urine Volume ◽  
Hydroxysteroid Dehydrogenase ◽  
Plasma Aldosterone ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Sustained Increase

The syndrome of inappropriate antidiuretic hormone (SIADH) is associated with water retention and hyponatremia. The kidney adapts via a transient natriuresis and persistent diuresis, i.e., vasopressin escape. Previously, we showed an increase in the whole kidney abundance of aldosterone-sensitive proteins, the α- and γ (70-kDa-band)-subunits of the epithelial Na+ channel (ENaC), and the thiazide-sensitive Na-Cl cotransporter (NCC) in our rat model of SIADH. Here we examine mean arterial pressure via radiotelemetry, aldosterone activity, and cortical vs. medullary ENaC subunit and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2) protein abundances in escape. Eighteen male Sprague-Dawley rats (300 g) were sham operated ( n = 6) or infused with desmopressin (dDAVP; n = 12, a V2 receptor-selective analog of AVP). After 4 days, one-half of the rats receiving dDAVP were switched to a liquid diet, i.e., water loaded (WL) for 5–7 additional days. The WL rats had a sustained increase in urine volume and blood pressure (122 vs. 104 mmHg, P < 0.03, at 7 days). Urine and plasma aldosterone levels were increased in the WL group to 844 and 1,658% of the dDAVP group, respectively. NCC and α- and γ-ENaC (70-kDa band) were increased significantly in the WL group (relative to dDAVP), only in the cortex. β- and γ-ENaC (85-kDa band) were increased significantly by dDAVP in cortex and medulla relative to control. 11β-HSD-2 was increased by dDAVP in the cortex and not significantly affected by water loading. These changes may serve to attenuate Na+ losses and ameliorate hyponatremia in vasopressin escape.

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