scholarly journals Effect of Vasopressin on the Hypothalamic-Pituitary-Adrenal Axis in ADPKD Patients during V2 Receptor Antagonism

2020 ◽  
Vol 51 (11) ◽  
pp. 861-870
Author(s):  
Judith E. Heida ◽  
Isidor Minović ◽  
Martijn van Faassen ◽  
Ido P. Kema ◽  
Wendy E. Boertien ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Kidney Function ◽  
Hpa Axis ◽  
Fold Increase ◽  
Receptor Activation ◽  
Healthy Controls ◽  
Hypothalamic Pituitary Adrenal ◽  
V2 Receptor ◽  
Autosomal Dominant Polycystic Kidney ◽  
Glucocorticoid Production

<b><i>Background:</i></b> Patients with autosomal dominant polycystic kidney disease (ADPKD) are treated with a vasopressin V2 receptor antagonist (V2RA) to slow disease progression. This drug increases vasopressin considerably in these patients with already elevated baseline levels. Vasopressin is known to stimulate the hypothalamic-pituitary-adrenal (HPA) axis through V1 and V3 receptor activation. It is unknown whether this increase in vasopressin during V2RA treatment affects glucocorticoid production. <b><i>Methods:</i></b> Twenty-seven ADPKD patients were studied on and off treatment with a V2RA and compared to age- and sex-matched healthy controls and IgA nephropathy patients, the latter also matched for kidney function. Vasopressin was measured by its surrogate copeptin. Twenty-four-hour urinary excretions of cortisol, cortisone, tetrahydrocortisone, tetrahydrocortisol, allotetrahydrocortisol, and the total glucocorticoid pool were measured. <b><i>Results:</i></b> At baseline, ADPKD patients demonstrated a higher copeptin concentration in comparison with healthy controls, while urinary excretion of cortisol and cortisone was lower (medians of 0.23 vs. 0.34 μmol/24 h, <i>p</i> = 0.007, and 0.29 vs. 0.53 μmol/24 h, <i>p</i> &#x3c; 0.001, respectively). There were no differences in cortisol and cortisone excretion compared to IgA nephropathy patients. Cortisol, cortisone, and total glucocorticoid excretions correlated with kidney function (<i>R</i> = 0.37, 0.58, and 0.19, respectively; all <i>p</i> &#x3c; 0.05). Despite that V2RA treatment resulted in a 3-fold increase in copeptin, only cortisone excretion increased (median of 0.44 vs. baseline 0.29 μmol/24 h, <i>p</i> &#x3c; 0.001), whereas no changes in cortisol or total glucocorticoid excretion were observed. <b><i>Conclusions:</i></b> Increased concentration of vasopressin in ADPKD patients at baseline and during V2RA treatment does not result in activation of the HPA axis. The impaired glucocorticoid production in these patients is related to their degree of kidney function impairment.

Effects of prolonged exendin-4 administration on hypothalamic-pituitary-adrenal axis activity and water balance

2013 ◽  
Vol 304 (10) ◽  
pp. E1105-E1117 ◽  
Author(s):  
Manuel Gil-Lozano ◽  
Marina Romaní-Pérez ◽  
Verónica Outeiriño-Iglesias ◽  
Eva Vigo ◽  
Patricia L. Brubaker ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Hpa Axis ◽  
Stress Responses ◽  
Fold Increase ◽  
Acute Administration ◽  
Sprague Dawley ◽  
Hypothalamic Pituitary Adrenal ◽  
Sprague Dawley Rats ◽  
Glucagon Like Peptide 1 ◽  
Hpa Axis Activity

Exendin-4 (Ex-4) is a natural agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently being used as a treatment for type 2 diabetes mellitus due to its insulinotropic properties. Previous studies have revealed that acute administration of both GLP-1 and, in particular, Ex-4 potently stimulates hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, the effects of prolonged Ex-4 exposure on HPA function were explored. To this end, Sprague-Dawley rats were subjected to a daily regimen of two Ex-4 injections (5 μg/kg sc) for a minimum of 7 days. We found that subchronic Ex-4 administration produced a number of effects that resemble chronic stress situations, including hyperactivation of the HPA axis during the trough hours, disruption of glucocorticoid circadian secretion, hypertrophy of the adrenal gland, decreased adrenal gland sensitivity, impaired pituitary-adrenal stress responses, and reductions in both food intake and body weight. In addition, a threefold increase in diuresis was observed followed by a 1.5-fold increase in water intake; these latter effects were abolished by adrenalectomy. Together, these findings indicate that Ex-4 induces a profound dysregulation of HPA axis activity that may also affect renal function.

Effect of Arginine on the Hypothalamic–Pituitary–Adrenal Axis in Individuals With and Without Vasopressin Deficiency

2020 ◽  
Vol 105 (7) ◽  
pp. e2327-e2336
Author(s):  
Katja Bologna ◽  
Nicole Cesana-Nigro ◽  
Julie Refardt ◽  
Cornelia Imber ◽  
Deborah R Vogt ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Hpa Axis ◽  
Pituitary Hormones ◽  
University Hospital ◽  
Healthy Controls ◽  
Arginine Infusion ◽  
Hypothalamic Pituitary Adrenal ◽  
Primary Polydipsia ◽  
Patients With Diabetes ◽  
Different Response

Abstract Context Arginine stimulates pituitary hormones, like growth hormone and vasopressin, but its effect on the hypothalamic–pituitary–adrenal (HPA) axis is unknown. Arginine may also stimulate the HPA axis, possibly through a mechanism involving vasopressin. Objective To investigate the effect of arginine on adrenocorticotropic hormone (ACTH) and cortisol in subjects with and without vasopressin deficiency. Design Prospective study, University Hospital Basel. Participants 38 patients with central diabetes insipidus, 58 patients with primary polydipsia, and 50 healthy controls. Intervention Arginine infusion with measurement of ACTH, cortisol and copeptin at baseline and 30, 45, 60, 90, and 120 minutes. Results We found different response patterns to arginine: in patients with diabetes insipidus (and low stimulated copeptin levels) median (interquartile range [IQR]) ACTH and cortisol increased from 22.9 (16.8, 38.7) to 36.6 (26.2, 52.1) ng/L and from 385 (266, 463) to 467 (349, 533) nmol/L, respectively. In contrast, median (IQR) ACTH and cortisol levels decreased in patients with primary polydipsia (despite high stimulated copeptin levels): ACTH from 17.3 (12.3, 23) to 14.8 (10.9, 19.8) ng/L and cortisol from 343 (262, 429) to 272 (220.8, 360.3) nmol/L; likewise, in healthy controls: ACTH from 26.5 (17.6, 35.7) to 14.8 (12.1, 22.7) ng/L and cortisol from 471 (393.3, 581.8) to 301.5 (206.5, 377.8) nmol/L. Conclusion Diabetes insipidus is associated with increased responsiveness of ACTH/cortisol to arginine. In contrast, arginine does not stimulate the HPA axis in healthy controls or in primary polydipsia.

Neuroimmunological Effects of Exposure to Methylmercury Forms in the Sprague-Dawley Rats. Activation of the Hypothalamic-Pituitary-Adrenal Axis and Lymphocyte Responsiveness

1997 ◽  
Vol 13 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Hector G. Ortega ◽  
Manuel Lopez ◽  
Atsushi Takaki ◽  
Qin-Heng Huang ◽  
Akira Arimura ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Low Dose ◽  
Fold Increase ◽  
Exposed Group ◽  
Blood Levels ◽  
High Dose ◽  
Sprague Dawley ◽  
Short Term ◽  
Hypothalamic Pituitary Adrenal ◽  
Short Term Exposure

The effects of different methylmercury (MeHg) forms on the immune system and the hypothalamic pituitary adrenal (HPA) axis were assessed. The lymphocyte response to Concanavalin A (Con A) stimulation, blood levels of interleukin-6 (IL-6), adrenocorticotrophin hormone (ACTH), and corticosterone in the presence of different MeHg compounds was measured. Rats were exposed to methylmercury sulfide [(MeHg)2S] and methylmercury chloride (MeHgCl) at concentrations of 5 and 500 μg per liter in the drinking water for 8 or 16 weeks. Short-term exposure (8 weeks) at both, low- and high-doses of (MeHg)2S significantly enhanced lymphocyte responsiveness. MeHgCl only induced increased lymphocyte responsiveness at the low-dose exposure. Circulating levels of IL-6 after short-term exposure were increased in the MeHgCl-exposed group. The HPA axis activation was demonstrated by increased levels of ACTH and corticosterone levels. This response was predominant in low-dose exposed animals. Long-term (16 weeks) exposure resulted in a reduction in lymphocyte proliferation after both low- and high-dose MeHgCl exposures. The (MeHg)2S exposure resulted in a 3-fold increase in the proliferative response. Levels of ACTH were elevated 3-fold in the (MeHg)2S-exposed group, and no increase of corticosterone was observed in the high-dose exposed group at 8 weeks, no effect of(MeHg)2S was observed at 16 weeks. The MeHgCl exposed group showed an increase in ACTH and corticosterone levels at 8 weeks; this response was not observed at 16 weeks. These data indicate that exposure to MeHg compounds enhances T-cell proliferation in most of the cases, in a dose- and time-dependent fashion. Release of IL-6 also depends on the length of exposure. Early increases in circulating ACTH at 8 weeks also suggest activation of the HPA axis. This may contribute to the production of IL-6 and surveillance of regulatory homeostatic responses against environmental agents that mimic stress-like responses.

scholarly journals Kidney Function Reserve Capacity in Early and Later Stage Autosomal Dominant Polycystic Kidney Disease

2018 ◽  
Vol 13 (11) ◽  
pp. 1680-1692 ◽  
Author(s):  
A. Lianne Messchendorp ◽  
Marco van Londen ◽  
Jacob M. Taylor ◽  
Martin H. de Borst ◽  
Gerjan Navis ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Function ◽  
Autosomal Dominant ◽  
Early Stage ◽  
Reserve Capacity ◽  
Healthy Controls ◽  
Age Group ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Measured Gfr

Background and objectivesIt is assumed that in autosomal dominant polycystic kidney disease (ADPKD), kidney function remains in the normal range for several decades because of hyperfiltration of remnant nephrons. In this study, we investigate the extent to which patients with ADPKD hyperfilter.Design, setting, participants, & measurementsIn this cross-sectional study, we measured GFR as urinary clearance using continuous infusion of 125I-iothalamate. Kidney function reserve capacity was determined as increase in measured GFR after adding a dopamine infusion of 4.4–6 mg/h. Potential kidney donors were used as healthy controls and matched by age and sex to patients with ADPKD for comparisons across age groups and CKD stages. Hyperfiltration was defined by a loss of kidney function reserve capacity compared with healthy controls.ResultsA total of 300 participants were studied. In the youngest age group (18–29 years), measured GFR was not different between patients with ADPKD and healthy controls (103±21 versus 111±9 ml/min per 1.73 m2; P=0.14). In this age group kidney function reserve capacity was higher compared with healthy controls (11.1%±8.3% versus 5.3%±6.5%; P=0.04). Moreover, kidney function reserve capacity was similar to healthy controls in patients with ADPKD with early-stage disease (eGFR≥60 ml/min per 1.73 m2), either overall or when divided into fast or slow progressors according to their Mayo height-adjusted total kidney volume class. However, in patients with ADPKD, lower measured GFR was associated with lower kidney function reserve capacity (β=1.0 [95% confidence interval, 0.5 to 1.5] % per 10 ml/min per 1.73 m2; P<0.001). Kidney function reserve capacity was therefore lower compared with healthy controls at older age and later CKD stages.ConclusionsPatients with early-stage ADPKD, either classified as having rapidly or slowly progressive disease, are able to increase their GFR in response to dopamine. Hyperfiltration, defined by a loss of kidney function reserve capacity, may therefore not be an early phenomenon in ADPKD.

MO230A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED STUDY OF ATRASENTAN IN PATIENTS WITH IGA NEPHROPATHY (THE ALIGN STUDY)

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hiddo Lambers Heerspink ◽  
Donald Kohan ◽  
Richard Lafayette ◽  
Adeera Levin ◽  
Hong Zhang ◽  
...  
Keyword(s):  
High Risk ◽  
Kidney Disease ◽  
Iga Nephropathy ◽  
Kidney Function ◽  
Receptor Activation ◽  
End Stage Kidney Disease ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
End Stage

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally and an important cause of chronic kidney disease (CKD). Up to 40% of IgAN patients are at risk of progressing to end-stage kidney disease (ESKD) and proteinuria is the strongest predictor of progression. There are no approved therapies for IgAN, leaving an important need for new strategies to lower proteinuria and preserve kidney function in high-risk patients. Endothelin A (ETA) receptor activation drives proteinuria, along with kidney inflammation and fibrosis. Atrasentan, a potent and selective ETA antagonist, has been studied extensively in &gt;5,000 patients with type 2 diabetes and kidney disease (DKD), demonstrating clinically significant and sustained reductions in proteinuria when administered on top of a maximum tolerated dose of RAS inhibitor (RASi). In a global Phase 3 outcome study in DKD (SONAR), atrasentan demonstrated a 35% reduced risk of the primary composite outcome of doubling of serum creatinine or end stage kidney disease (95% CI: 0.49, 0.88; P = 0.005). The most common adverse event was fluid retention. Selective ETA blockade represents a promising approach to reduce proteinuria and preserve kidney function in high risk IgAN patients. This is a presentation of a global, phase 3, double-blind, placebo-controlled trial to determine the effect of atrasentan in IgAN patients at high risk of kidney function loss. Method Approximately 320 patients across North America, South America, Europe, and Asia-Pacific with biopsy-proven IgAN will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks. Patients will continue receiving a maximally tolerated and stable dose of a RAS inhibitor as standard of care. The study will also include patients that are unable to tolerate RAS inhibitor therapy. Additional eligibility criteria include urine protein creatinine ratio (UPCR) ≥1 g/g and eGFR ≥30 mL/min/1.73 m2. Participants will have study assessments over two and a half years with options for remote study visits using telemedicine and home health visits. The primary objective is to evaluate the effect of atrasentan versus placebo on proteinuria at Week 24. Secondary objectives include evaluating the change from baseline in eGFR, safety, and tolerability, and quality of life. Results N/A Conclusion N/A

Effects of alprazolam on cholecystokinin-tetrapeptide (CCK-4) induced panic and hypothalamic-pituitary-adrenal (HPA) axis activity

2004 ◽  
Vol 36 (05) ◽  
Author(s):  
D Eser ◽  
P Zwanzger ◽  
S Aicher ◽  
C Schüle ◽  
TC Baghai ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Hypothalamic Pituitary Adrenal ◽  
Hpa Axis Activity

scholarly journals Dream Recall/Affect and the Hypothalamic–Pituitary–Adrenal Axis

2021 ◽  
Vol 3 (3) ◽  
pp. 403-408
Author(s):  
Athanasios Tselebis ◽  
Emmanouil Zoumakis ◽  
Ioannis Ilias
Keyword(s):  
Hpa Axis ◽  
Glucocorticoid Receptors ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Free Form ◽  
Dream Recall ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Concise Review ◽  
Pathological Conditions ◽  
Pituitary Adrenal Axis

In this concise review, we present an overview of research on dream recall/affect and of the hypothalamic–pituitary–adrenal (HPA) axis, discussing caveats regarding the action of hormones of the HPA axis (mainly cortisol and its free form, cortisol-binding globulin and glucocorticoid receptors). We present results of studies regarding dream recall/affect and the HPA axis under physiological (such as waking) or pathological conditions (such as in Cushing’s syndrome or stressful situations). Finally, we try to integrate the effect of the current COVID-19 situation with dream recall/affect vis-à-vis the HPA axis.

scholarly journals Do Corticosteroid Injections for the Treatment of Pain Influence the Efficacy of mRNA COVID-19 Vaccines?

Pain Medicine ◽  
2021 ◽  
Vol 22 (4) ◽  
pp. 994-1000
Author(s):  
Haewon Lee ◽  
Jennifer A Punt ◽  
David C Miller ◽  
Ameet Nagpal ◽  
Clark C Smith ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Ribonucleic Acid ◽  
Direct Evidence ◽  
Corticosteroid Injection ◽  
Vaccine Dose ◽  
Hypothalamic Pituitary Adrenal ◽  
Messenger Ribonucleic Acid ◽  
Corticosteroid Injections

Abstract Myth Corticosteroid injection for the treatment of pain and inflammation is known to decrease the efficacy of the messenger ribonucleic acid (mRNA) vaccines for coronavirus disease 2019 (COVID-19). Fact There is currently no direct evidence to suggest that a corticosteroid injection before or after the administration of an mRNA COVID-19 vaccine decreases the efficacy of the vaccine. However, based on the known timeline of hypothalamic-pituitary-adrenal (HPA) axis suppression following epidural and intraarticular corticosteroid injections, and the timeline of the reported peak efficacy of the Pfizer-BioNTech and Moderna vaccines, physicians should consider timing an elective corticosteroid injection such that it is administered no less than 2 weeks prior to a COVID-19 mRNA vaccine dose and no less than 1 week following a COVID-19 mRNA vaccine dose, whenever possible.

scholarly journals Genes and hormones of the hypothalamic–pituitary–adrenal axis in post-traumatic stress disorder. What is their role in symptom expression and treatment response?

2021 ◽  
Author(s):  
Susanne Fischer ◽  
Tabea Schumacher ◽  
Christine Knaevelsrud ◽  
Ulrike Ehlert ◽  
Sarah Schumacher
Keyword(s):  
Hpa Axis ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Ptsd Symptoms ◽  
Post Traumatic Stress ◽  
Alternative Treatments ◽  
Hypothalamic Pituitary Adrenal ◽  
Post Traumatic

Abstract Background Less than half of all individuals with post-traumatic stress disorder (PTSD) remit spontaneously and a large proportion of those seeking treatment do not respond sufficiently. This suggests that there may be subgroups of individuals who are in need of augmentative or alternative treatments. One of the most frequent pathophysiological findings in PTSD is alterations in the hypothalamic–pituitary–adrenal (HPA) axis, including enhanced negative feedback sensitivity and attenuated peripheral cortisol. Given the role of the HPA axis in cognition, this pattern may contribute to PTSD symptoms and interfere with key processes of standard first-line treatments, such as trauma-focused cognitive behavioural therapy (TF-CBT). Methods This review provides a comprehensive summary of the current state of research regarding the role of HPA axis functioning in PTSD symptoms and treatment. Results Overall, there is preliminary evidence that hypocortisolaemia contributes to symptom manifestation in PTSD; that it predicts non-responses to TF-CBT; and that it is subject to change in parallel with positive treatment trajectories. Moreover, there is evidence that genetic and epigenetic alterations within the genes NR3C1 and FKBP5 are associated with this hypocortisolaemic pattern and that some of these alterations change as symptoms improve over the course of treatment. Conclusions Future research priorities include investigations into the role of the HPA axis in day-to-day symptom variation, the time scale in which biological changes in response to treatment occur, and the effects of sex. Furthermore, before conceiving augmentative or alternative treatments that target the described mechanisms, multilevel studies are warranted.

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