Impaired Renal Concentrating Ability in Hypothyroid Man

Vaamonde, Carlos A.; Michael, Ulrich F.; Oster, James R.; Sebastianelli, Mario J.; Vaamonde, Liliana S.; Klingler, Eugene L.; Papper, Solomon

doi:10.1159/000180744

Cited by 16 publications

(13 citation statements)

References 17 publications

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“…These events, which impair urinary dilution in advanced hypothyroidism, override the defect in urinary concentrating capacity, which also has been observed with hypothyroidism (1,2). In the present study, a model of moderate hypothyroidism was investigated in which neither hyponatremia nor a diminished GFR occurred, but a reversible decrease in maximal urine concentration was observed.…”

Section: Discussionmentioning

confidence: 76%

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Urinary Concentrating Defect in Hypothyroid Rats

Cadnapaphornchai¹,

Kim²,

Gurevich³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Hypothyroidism is associated with impaired urinary concentrating ability in humans and animals. The purpose of this study was to examine protein expression of renal sodium chloride and urea transporters and aquaporins in hypothyroid rats (HT) with diminished urinary concentration as compared with euthyroid controls (CTL) and hypothyroid rats replaced with L-thyroxine (HTϩT). Hypothyroidism was induced by aminotriazole administration. Body weight, water intake, urine output, solute and urea excretion, serum and urine osmolality, serum creatinine, 24-h creatinine clearance, and fractional excretion of sodium were comparable among the three groups. However, with 36 h of water deprivation, HT rats demonstrated significantly greater urine flow rates and decreased urine and medullary osmolality as compared with CTL and HTϩT rats at comparable plasma vasopressin concentrations. Western blot analyses revealed decreased renal protein abundance of transporters, including Na-K-2Cl, Na-K-ATPase, and NHE3, in HT rats as compared with CTL and HTϩT rats. Protein abundance of renal AQP1 and urea transporters UTA 1 and UTA 2 did not differ significantly among study groups. There was however a significant decrease in protein abundance of AQP2, AQP3, and AQP4 in HT rats as compared with CTL and HTϩT rats. These findings demonstrate a decrease in the medullary osmotic gradient secondary to impaired countercurrent multiplication and downregulation of aquaporins 2, 3, and 4 as contributors to the urinary concentrating defect in the hypothyroid rat.Hypothyroidism is a very common clinical disorder that is associated with abnormalities in many organs, including the kidney. The ability to conserve water during periods of fluid deprivation is an important function of the kidney. Hypothyroidism has been associated with an impaired urinary concentrating capacity (1,2). However, the mechanisms of this defect at the cellular and molecular level have not been defined.In the present study, the effect of hypothyroidism in rats on the pivotal components of the urinary concentrating mechanism have been examined and compared with euthyroid animals. These components during fluid deprivation include release of the antidiuretic hormone, arginine vasopressin (AVP), and upregulation of the abundance of aquaporin-2 (AQP2) water channels in the principal cells of the collecting duct. Activation of the countercurrent concentrating mechanism, which is initiated by increased sodium-potassium-2 chloride (Na-K-2Cl) co-transporter in the water impermeable ascending limb, creates the osmotic driving force for passive water reabsorption across the collecting duct. There are also roles for other water channels, including aquaporins 1, 3, and 4, and for urea transporters in urinary concentration. The present study was undertaken to define the effect of hypothyroidism on these various molecular events during fluid deprivation in the rat. Materials and Methods Animal ModelThe study protocol was approved by the University of Colorado Institutional Animal Ca...

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Section: Discussionmentioning

confidence: 76%

“…The ability to conserve water during periods of fluid deprivation is an important function of the kidney. Hypothyroidism has been associated with an impaired urinary concentrating capacity (1,2). However, the mechanisms of this defect at the cellular and molecular level have not been defined.…”

mentioning

confidence: 99%

Urinary Concentrating Defect in Hypothyroid Rats

Cadnapaphornchai¹,

Kim²,

Gurevich³

et al. 2003

Journal of the American Society of Nephrology

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“…We found that after TX, renal AT1 receptor expression was decreased at both the mRNA and protein level. In adult human and animal models of hypothyroidism, renal function is also altered, resulting in decreased renal blood flow, glomerular filtration rate, and sodium reabsorption (7,31,32,43), as well as impaired concentrating and diluting capacity (24,60). These outcomes are likely to be mediated in part by associated changes in AT1 receptor expression.…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep

Chen

Carey

Valego

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Fetal renin-angiotensin system (RAS) activity is developmentally regulated, increasing in late gestation toward term. At the same time, fetal hemodynamic parameters change, with blood pressure increasing and heart rate decreasing. During this period, fetal plasma thyroid hormone concentrations also increase significantly. In this study we utilized the technique of thyroidectomy (TX), which removes thyroid hormone from the circulation, to investigate the importance of thyroid hormone on the developmental changes in the RAS (in plasma, kidney, heart, and lung) and hemodynamic regulation in fetal sheep. TX was performed at 120 days of gestational age (dGA), and control fetuses were sham operated. Immediately before necropsy (ϳ137 dGA), fetuses were infused with isoproterenol and the hemodynamic responses were noted. TX significantly decreased plasma thyroid hormone concentrations and renal renin mRNA and renal active renin levels but did not change fetal plasma active renin levels. TX decreased both angiotensin II receptor subtype 1 (AT1) mRNA and protein levels in kidney and lung but not in the left ventricle. TX also was associated with increased ANG II receptor subtype 2 (AT2) mRNA and protein at the 44-kDa band in kidney, whereas AT2 protein was decreased at the 78-kDa level in kidney and lung tissue only. TX fetuses had significantly lower basal mean arterial blood pressures (MAP) and heart rates than controls. Isoproterenol infusion decreased MAP in TX fetuses. These findings support the hypothesis that thyroid hormone is important in modulating maturation of RAS and cardiovascular function in the late-gestation fetal sheep. renin-angiotensin system; fetus THE RENIN-ANGIOTENSIN SYSTEM (RAS), composed of renin, angiotensinogen, ANG I-converting enzyme (ACE), ANG II, and the ANG II receptor subtypes, plays an important role in regulating fetal growth and development, particularly with respect to the cardiovascular system, and electrolyte homeostatic mechanisms (2,22,48). It is well established that components of the fetal RAS are developmentally regulated and exhibit increased activity in late gestation (12,56,57,63). Changes in expression of the levels of ANG II receptor subtypes 1 and 2 (AT1 and AT2) are opposite, with AT1 mRNA low in early gestation and rising to a plateau later, before increasing rapidly close to term, whereas AT2 expression is highest during midpregnancy and then decreases gradually thereafter (46, 47). Tissue-dependent differences also are apparent (18,40,66). The mechanisms underlying these ontogenic patterns of expression are not clear.In fetal sheep, the changes in components of RAS activity appear temporally related to changes in thyroid hormone concentrations, which are low before 130 -135 days of gestational age (dGA) and then markedly increased toward parturition (19). A similar pattern of change is seen in humans (44). These observations suggest that thyroid hormone may be important in regulating ontogenic changes in renin and ANG II receptors.Thyroid hormone also exerts broad eff...

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“…Hypothyroidism has been associated with impaired urinary concentrating capacity in animals and humans [3-6]. Short-term hypothyroidism in rats results in a diminished medullary osmotic driving force for passive water movement across the collecting duct.…”

Section: Introductionmentioning

confidence: 99%

“…Only a few studies on the urinary concentrating defect in hypothyroidism have been performed in patients with autoimmune thyroid disease [5, 6]. A small study ( n = 4) of patients with hypothyroidism revealed a urinary concentrating defect after 16 h of water deprivation [5].…”

Section: Introductionmentioning

confidence: 99%

Effects of Thyroid Hormone on Urinary Concentrating Ability

Massolt¹,

Salih²,

Beukhof³

et al. 2017

Eur Thyroid J

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Background: Hypothyroidism has been associated with impaired urinary concentrating ability. However, previous reports on thyroid hormone and urinary concentrating ability in humans only studied a limited number of patients with autoimmune thyroid disease or used healthy controls instead of paired analysis within the same patients. Objective: To study the urinary concentrating ability in athyreotic patients with differentiated thyroid cancer on and off levothyroxine treatment as they are exposed to different thyroid states as part of their treatment in the absence of an autoimmune disease. Design and Methods: We studied 9 patients (mean age of 42.7 years) during severe hypothyroid state (withdrawal of levothyroxine before radioactive iodine therapy) and TSH-suppressed state (on levothyroxine therapy). At these two points, serum and urine samples were collected after 14 h of overnight fasting without any food or drink. Results: Serum and urine osmolality were not significantly different between on and off levothyroxine treatment. Serum creatinine levels were significantly higher in patients off versus on levothyroxine treatment (87.0 vs. 71.0 µmol/L, respectively; p = 0.044) and, correspondingly, the estimated glomerular filtration rate was significantly lower (89.6 vs. 93.1 mL/min, respectively; p = 0.038). Conclusion: Short-term, severe hypothyroidism has no effect on urinary concentrating ability. Our study confirms the well-known effects of thyroid hormone on serum creatinine concentrations.

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Impaired Renal Concentrating Ability in Hypothyroid Man

Cited by 16 publications

References 17 publications

Urinary Concentrating Defect in Hypothyroid Rats

Urinary Concentrating Defect in Hypothyroid Rats

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep

Effects of Thyroid Hormone on Urinary Concentrating Ability

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