Polyuria of thyrotoxicosis: Downregulation of aquaporin water channels and increased solute excretion

Wang, Weidong; Li, C; Summer, Sandra N.; Falk, Sandor; Schrier, Robert W.

doi:10.1038/sj.ki.5002475

Cited by 40 publications

(24 citation statements)

References 30 publications

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“…The ability to concentrate urine may be diminished in patients with thyrotoxicosis but does not present any clinical significance (68,69). Moreover, the combined effect of the direct down regulation of aquaporin 1 and 2 by thyroid hormones in excess combined with the increased blood pressure, CO and RBF may cause polyuria (70). The hypertrophy and hyperplasia in combination with an increased activity lead to damage of the tubular cells.…”

Section: Thyroid Disorders and Tubular Functionmentioning

confidence: 99%

The Thyroid and the Kidney: A Complex Interplay in Health and Disease

et al. 2014

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Thyroid hormones may directly affect the kidney and altered kidney function may also contribute to thyroid disorders. The renal manifestations of thyroid disorders are based on hemodynamic alterations or/and to direct effects of thyroid hormones. The renin-angiotensin system plays a crucial role in the cross-talk between the thyroid and the kidney. Hypothyroidism may be accompanied by an increase of serum creatinine and reduction of glomerular filtration rate (GFR), whereas hyperthyroidism may increase GFR. Treatment of thyroid disorders may lead to normalization of GFR. Primary and subclinical hypothyroidism and low triiodothyronine (T3) syndrome are common features in patients with chronic kidney disease (CKD). In addition low levels of thyroid hormones may predict a higher risk of cardiovascular and overall mortality in patients with end-stage renal disease. The causal nature of this correlation remains uncertain. In this review, special emphasis is given to the thyroid pathophysiology, its impact on kidney function and CKD and the interpretation of laboratorial findings of thyroid dysfunction in CKD.

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Section: Thyroid Disorders and Tubular Functionmentioning

confidence: 99%

The Thyroid and the Kidney: A Complex Interplay in Health and Disease

et al. 2014

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“…10,11 Conversely, kidney to body weight ratios in hyperthyroid animals increase by as much as 30%. 12,13 Children with congenital hypothyroidism have reduced renal mass and a higher prevalence of renal and urologic abnormalities, including dysplastic kidney, renal agenesis, ectopic kidney, hydronephrosis, posterior urethral valves, and hypospadias. 14 Mutations in the gene encoding Pax8, a transcription factor important for normal development and function, may, in some patients, be the link between congenital hypothyroidism and renal dysmorphogenesis.…”

Section: Impact Of Thyroid Hormone On Renal Growth and Developmentmentioning

confidence: 99%

The Renal Manifestations of Thyroid Disease

Mariani

Berns

2012

Journal of the American Society of Nephrology

238

200

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Thyroid hormones influence renal development, kidney structure, renal hemodynamics, GFR, the function of many transport systems along the nephron, and sodium and water homeostasis. These effects of thyroid hormone are in part due to direct renal actions and in part are mediated by cardiovascular and systemic hemodynamic effects that influence kidney function. As a consequence, both hypothyroidism and hyperthyroidism associate with clinically important alterations in kidney function and have relevance to its assessment. Disorders of thyroid function have also been linked to development of immune-mediated glomerular injury, and alterations in thyroid hormones and thyroid hormone testing occur in patients with kidney disease.

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“…Hyperthyroid patients may exhibit polyuria (46) and this has also been shown to occur in the hyperthyroid rat (47). Somewhat surprising, however, this polyuria in the hyperthyroid rat is associated with an upregulation of Na-K-Cl transporter.…”

Section: Hypo-and Hyperthyroidismmentioning

confidence: 97%

“…The animals are, however, hypertensive and have an increase in solute excretion, even in the presence of control of water and food intake, most likely secondary to increased blood pressure and catabolism. The diminished urinary concentration and polyuria in hyperthyroid rats was associated with a downregulation of AQP2 and a persistent solute diuresis (47). Both of these potential mediators of polyuria associated with hyperthyroidism may be related to the effect of the increase in blood pressure which has been shown to increase salt and water delivery to the distal nephron (48) and decreased AQP2 expression (49).…”

Section: Hypo-and Hyperthyroidismmentioning

confidence: 99%

Vasopressin and Aquaporin 2 in Clinical Disorders of Water Homeostasis

Schrier

2008

Seminars in Nephrology

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The cloning of the V2 vasopressin receptor was a major advance in understanding the mechanisms involved in regulation of solute-free water excretion by arginine vasopressin (AVP) (1). Subsequently, mutations of the V2 receptor gene were found to account for approximately 85% of cases of congenital nephrogenic diabetes insipidus (2). The mechanisms whereby AVP activates the V2 receptor on the basolateral membrane of the principal cells of the collecting duct and leads to increased water permeability of the apical membrane were, however, quite perplexing. The water transport across the bilipid apical membrane of the principal cells was too fast to be due to diffusion alone. Thus, the shuttle hypothesis was proposed whereby theoretical water channels would be moved from the cytoplasm to the apical membrane of the principal cells by AVP (3). The discovery of the first water channel, aquaporin 1 (AQP1), by Agre and associates led to great excitement in the biomedical community and the awarding of the Nobel Prize in Chemistry in 2003 to Peter Agre (4). Subsequently, aquaporin 2 (AQP2) was identified by Sasaki et al. in the principal cells of the collecting duct (5). Further investigations have demonstrated that AVP is the major regulator of the AQP2 water channels (6). Activation of the V2 receptor on the principal cells of the collecting duct by AVP is associated with a cascade of events involving adenylyl cyclase-mediated cyclic AMP (Figure 1) (7) which leads to both short term and long term regulation of AQP2 (8,9). The short term regulation of AVP involves shuttling the AQP2 containing vesicles from the cytoplasm to the apical membrane. With suppression of vasopressin these apical AQP2 water channels then undergo endocytosis into the cytoplasm (3). The 5' flanking region of the AQP2 gene has a cyclic AMP response element which is involved in the long term upregulation of AQP2 protein expression by AVP (9).The discovery of non-peptide antagonists to the V2 receptor have added yet another important dimension to the understanding of total body water homeostasis (10). These V2 receptor antagonists are agents that specifically block the action of AVP in humans. The several V2 receptor antagonists presently involved in clinical studies are shown in Table 1 (11). In contrast to diuretics, which enhance urine water and electrolyte excretion, the V2 receptor antagonists increase electrolyte-free water excretion.A relative excess of total body water to cation concentration leads to hyponatremia in many clinical circumstances. In fact, hyponatremia is the most frequent electrolyte disturbance in hospitalized patients (12). V2 receptor antagonists have substantial clinical implications, since the majority of the hyponatremic states are due to the non-osmotic release of AVP (13). These V2 receptor antagonists have also been important vehicles to understand several waterPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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Polyuria of thyrotoxicosis: Downregulation of aquaporin water channels and increased solute excretion

Cited by 40 publications

References 30 publications

The Thyroid and the Kidney: A Complex Interplay in Health and Disease

The Thyroid and the Kidney: A Complex Interplay in Health and Disease

The Renal Manifestations of Thyroid Disease

Vasopressin and Aquaporin 2 in Clinical Disorders of Water Homeostasis

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