SALT AND WATER METABOLISM AND NEUROHYPOPHYSEAL VASOPRESSOR ACTIVITY IN MICE WITH HEREDITARY NEPHROGENIC DIABETES INSIPIDUS

1972 ◽  
Vol 69 (3) ◽  
pp. 434-444 ◽  
Author(s):  
D. V. Naik
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Urine Osmolality ◽  
Water Metabolism ◽  
Urine Sodium ◽  
Adh Activity ◽  
Vasopressor Activity ◽  
Sodium And Potassium ◽  
Total Excretion

ABSTRACT Three genotypes of mice, VII Os/+, DI +/+ and DI Os/+, with nephrogenic (vasopressin resistant) diabetes insipidus (DI) are compared to a normal VII +/+ strain with respect to water intake, urine output, urine osmolality, urine sodium and potassium, and the extractable vasopressor (ADH) activity from the neurohypophysis. From the results obtained, it is confirmed that the severely diabetic DI Os/+ mice produce large volumes of dilute, hypotonic urine and have a 2½ fold vasopressor increase as compared to normal VII +/+ mice, whereas, the mildly diabetic VII Os/+ and DI +/+ stand in between the DI Os/+ and VII +/+ with intermediate volumes of hypertonic urine and a vasopressor increase of 1⅓ and 1½ fold respectively. Further, a parallelism between the severity of diabetes insipidus and increased vasopressor activity is demonstrated in this study. The total excretion of sodium in the urine of VII Os/+ and DI Os/+ is higher than that of the VII +/+ and DI +/+ mice. This natriuresis is associated with Os gene and furthermore, its possible hypothalamic involvement is discussed. The increase of ADH in these hereditary nephrogenic diabetes insipidus mice is a new syndrome and the possible role of other factors involved is discussed.

scholarly journals MON-LB65 Lithium: The Culprit of Multiple Endocrinopathies

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Alice Yau ◽  
Gul Bahtiyar ◽  
Giovanna Rodriguez ◽  
Jose R Martinez Escudero
Keyword(s):  
Bipolar Disorder ◽  
Diabetes Insipidus ◽  
Mental Status ◽  
Nephrogenic Diabetes Insipidus ◽  
Kidney Injury ◽  
Urine Osmolality ◽  
Altered Mental Status ◽  
Clinical Findings ◽  
Volume Depletion ◽  
Collecting Tubules

Abstract Background: Lithium, commonly used to treat various psychiatric disorders such as bipolar disorder, can cause acute toxicity that presents with nausea, vomiting and diarrhea. Lithium can also cause life-threatening endocrine abnormalities, including hypercalcemia, hypernatremia, and both hypo- and hyperthyroidism. Clinical Case: A 61-year old female with hypothyroidism, bipolar disorder, hyperparathyroidism with two-gland parathyroidectomy on lithium for over 30 years presented with altered mental status. Initial labs revealed elevated creatinine 1.92 mg/dL (0.8-2.00mg/dL) compared to baseline 0.82 mg/dL, sodium 154 mg/dL (135-147 mg/dL), Corrected calcium 11.7 mg/dL (8.5-10.5 mg/dL), PTH 96 pg/mL (15-65 pg/mL), and high lithium levels 1.45 mmol/L (0.60-1.20 mmol/L). Further studies showed hypotonic polyuria with no increase in urine osmolality after desmopressin, consistent with nephrogenic diabetes insipidus. Lithium was held and she was treated with aggressive intravenous hydration with dextrose 5% water. Hypercalcemia is thought to result from increased secretion of PTH due to an increased set point at which calcium suppresses PTH release; this often resolves once lithium is stopped. Lithium can also unmask previously unrecognized mild hyperparathyroidism, and/or raise serum PTH concentrations independent of calcium levels.1 The drug interferes with the kidneys’ ability to concentrate urine in the collecting tubules by desensitizing response to antidiuretic hormone, causing diabetes insipidus. The resulting volume depletion from excessive urinary water loss in turn lead to acute kidney injury and hypernatremia.2 Hypothyroidism results from lithium-inhibited synthesis and release of thyroid hormones and decreases iodine trapping. Conclusion: Although these are infrequent complications of lithium use, they remain pertinent clinical findings to consider due to their morbidity. In this case, our patient may have avoided multiple chronic electrolyte abnormalities leading to altered mental status if lithium toxicity had been recognized earlier. References:1. García-Maldonado, Gerardo, and Rubén de Jesús Castro-García. “Endocrinological Disorders Related To The Medical Use Of Lithium. A Narrative Review”. Revista Colombiana De Psiquiatría (English Ed.), vol 48, no. 1, 2019, pp. 35-43. Elsevier BV, doi:10.1016/j.rcpeng.2018.12.005. 2. Tasci, E. “Lithium-Induced Nephrogenic Diabetes Insipidus Responsive To Desmopressin”. Acta Endocrinologica (Bucharest), vol 15, no. 2, 2019, pp. 270-271. ACTA Endocrinologica Foundation, doi:10.4183/aeb.2019.270.

Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality

2005 ◽  
Vol 288 (5) ◽  
pp. F912-F920 ◽  
Author(s):  
Yuqiang Ge ◽  
Dowahn Ahn ◽  
Peter K. Stricklett ◽  
Alisa K. Hughes ◽  
Masashi Yanagisawa ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Urine Volume ◽  
Urine Osmolality ◽  
Water Metabolism ◽  
Urinary Osmolality ◽  
Water Load ◽  
Endothelin 1 ◽  
Normal Water

In vitro studies suggest that endothelin-1 (ET-1) inhibits vasopressin (AVP)-stimulated water permeability in the collecting duct (CD). To evaluate the role of CD-derived ET-1 in regulating renal water metabolism, the ET-1 gene was selectively disrupted in the CD (CD ET-1 KO). During normal water intake, urinary osmolality (Uosm), plasma Na concentration, urine volume, and renal aquaporin-2 (AQP2) levels were unchanged, but plasma AVP concentration was reduced in CD ET-1 KO animals. CD ET-1 KO mice had impaired ability to excrete an acute, but not a chronic, water load, and this was associated with increased CD ET-1 mRNA in control, but not CD ET-1 KO, mice. In response to continuous infusion of 1-desamino-8-d-arginine vasopressin, CD ET-1 KO mice had greater increases in Uosm, V2 and AQP2 mRNA, and phosphorylation of AQP2. CD suspensions from CD ET-1 KO mice had enhanced AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ET-1 KO increases renal sensitivity to the urinary concentrating effects of AVP and suggest that ET-1 functions as a physiological autocrine regulator of AVP action in the CD.

scholarly journals Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic diabetes insipidus

JCI Insight ◽  
2017 ◽  
Vol 2 (7) ◽  
Author(s):  
Søren Brandt Poulsen ◽  
Tina Bøgelund Kristensen ◽  
Heddwen L. Brooks ◽  
Donald E. Kohan ◽  
Timo Rieg ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Adenylyl Cyclase ◽  
Nephrogenic Diabetes Insipidus

scholarly journals Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype.

1998 ◽  
Vol 9 (10) ◽  
pp. 1861-1872
Author(s):  
Y Ala ◽  
D Morin ◽  
B Mouillac ◽  
N Sabatier ◽  
R Vargas ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Three Dimensional ◽  
Urine Osmolality ◽  
Complete Loss ◽  
Loss Of Function ◽  
Hydrogen Bond Formation ◽  
Functional Studies ◽  
Three Dimensional Modeling

X-linked nephrogenic diabetes insipidus (NDI) is a rare disease with defective renal and extrarenal arginine vasopressin V2 receptor responses due to mutations in the AVPR2 gene in Xq28. To study the cause of loss of function of mutant V2 receptors, we expressed 12 mutations (N55H, L59P, L83Q, V88M, 497CC-->GG, deltaR202, I209F, 700delC, 908insT, A294P, P322H, P322S) in COS-7 cells. Eleven of these, including P322H, were characterized by a complete loss of function, but the mutation P322S demonstrated a mild clinical and in vitro phenotype. This was characterized by a late diagnosis without any growth or developmental delay and a significant increase in urine osmolality after intravenous 1-deamino[D-Arg8]AVP administration. In vitro, the P322S mutant was able to partially activate the Gs/adenylyl cyclase system in contrast to the other V2R mutants including P322H, which were completely inactive in this regard. This showed not only that Pro 322 is important for proper V2R coupling, but also that the degree of impairment is strongly dependent on the identity of the substituting amino acid. Three-dimensional modeling of the P322H and P322S mutant receptors suggested that the complete loss of function of the P322H receptor could be due, in part, to hydrogen bond formation between the His 322 side chain and the carboxyl group of Asp 85, which does not occur in the P322S receptor.

scholarly journals Partial nephrogenic diabetes insipidus associated with lithium therapy

2019 ◽  
Vol 12 (9) ◽  
pp. e231093 ◽  
Author(s):  
Eka Nandoshvili ◽  
Steve Hyer ◽  
Nikhil Johri
Keyword(s):  
Diabetes Insipidus ◽  
Affective Disorder ◽  
Water Intake ◽  
Intramuscular Injection ◽  
Nephrogenic Diabetes Insipidus ◽  
Water Deprivation ◽  
Bipolar Affective Disorder ◽  
Urine Osmolality ◽  
Urinary Concentrating Ability

A 40-year-old Caucasian man developed excessive thirst and polyuria particularly at night over the preceding 6 months. He had been taking lithium for 16 years for the treatment of bipolar affective disorder. Investigations revealed subnormal maximum urinary concentrating ability after 8 hours of water deprivation and only a borderline response of urine osmolality to exogenous desmopressin given by intramuscular injection. A plasma copeptin concentration was elevated at 23 pmol/L. These results were consistent with partial nephrogenic diabetes insipidus. He was encouraged to increase his water intake as dictated by his thirst. In addition, he received amiloride with some improvement in his symptoms. Clinicians should be aware of the risk of nephrogenic diabetes insipidus with long-term lithium use and seek confirmation by a supervised water deprivation test augmented with a baseline plasma copeptin. If increased water intake is insufficient to control symptoms, amiloride may be considered.

scholarly journals Physiology and Pathophysiology of Renal Aquaporins

1999 ◽  
Vol 10 (3) ◽  
pp. 647-663
Author(s):  
SØREN NIELSEN ◽  
TAE-HWAN KWON ◽  
BIRGITTE MØNSTER CHRISTENSEN ◽  
DOMINIQUE PROMENEUR ◽  
JØRGEN FRØKIÆR ◽  
...  
Keyword(s):  
Water Balance ◽  
Diabetes Insipidus ◽  
Proximal Tubule ◽  
Nephrogenic Diabetes Insipidus ◽  
Collecting Duct ◽  
Water Channels ◽  
Apical Plasma Membrane ◽  
Water Reabsorption ◽  
Balance Disorders

Abstract. The discovery of aquaporin membrane water channels by Agre and coworkers answered a long-standing biophysical question of how water specifically crosses biologic membranes, and provided insight, at the molecular level, into the fundamental physiology of water balance and the pathophysiology of water balance disorders. Of nine aquaporin isoforms, at least six are known to be present in the kidney at distinct sites along the nephron and collecting duct. Aquaporin-1 (AQP1) is extremely abundant in the proximal tubule and descending thin limb, where it appears to provide the chief route for proximal nephron water reabsorption. AQP2 is abundant in the collecting duct principal cells and is the chief target for vasopressin to regulate collecting duct water reabsorption. Acute regulation involves vasopressin-regulated trafficking of AQP2 between an intracellular reservoir and the apical plasma membrane. In addition, AQP2 is involved in chronic/adaptational regulation of body water balance achieved through regulation of AQP2 expression. Importantly, multiple studies have now identified a critical role of AQP2 in several inherited and acquired water balance disorders. This concerns inherited forms of nephrogenic diabetes insipidus and several, much more common acquired types of nephrogenic diabetes insipidus where AQP2 expression and/or targeting are affected. Conversely, AQP2 expression and targeting appear to be increased in some conditions with water retention such as pregnancy and congestive heart failure. AQP3 and AQP4 are basolateral water channels located in the kidney collecting duct, and AQP6 and AQP7 appear to be expressed at lower abundance at several sites including the proximal tubule. This review focuses mainly on the role of AQP2 in water balance regulation and in the pathophysiology of water balance disorders.

EVIDENCE THAT THE ANTIDIURETIC SUBSTANCE IN THE PLASMA OF CHILDREN WITH NEPHROGENIC DIABETES INSIPIDUS IS ANTIDIURETIC HORMONE

PEDIATRICS ◽  
1963 ◽  
Vol 32 (3) ◽  
pp. 384-388
Author(s):  
Malcolm A. Holliday ◽  
Charles Burstin ◽  
Jean Harrah
Keyword(s):  
Diabetes Insipidus ◽  
Antidiuretic Hormone ◽  
Nephrogenic Diabetes Insipidus ◽  
Water Deprivation ◽  
Jugular Vein ◽  
Urine Osmolality ◽  
Urine Flow ◽  
Antidiuretic Activity ◽  
Antecubital Vein ◽  
Assay Technique

The antidiuretic activity in the plasma of four children with nephrogenic diabetes insipidus was measured by a rat assay technique. The evidence presented to indicate that this activity was due to antidiuretic hormone (ADH) was as follows: (a) the activity was higher in jugular vein plasma than in femoral or antecubital vein plasma, (b) it was high when the children were thirsted and decreased when they drank water, (c) it was destroyed when the plasma was incubated with thioglycollate, and (d) it was ultrafilterable, and vasopressin (Pitressin), when injected, was distributed as though it was ultrafilterable. When the children were given vasopressin, there was no change in urine flow or osmolality, but plasma antidiuretic activity was higher than it was when water deprivation led to a reduction in urine flow and an increase in urine osmolality. The inference of these findings is that ADH is secreted normally in children with nephrogenic diabetes insipidus, it is ultrafilterable, but it is not a factor in modifying urine flow in response to dehydration.

scholarly journals Nephrogenic diabetes insipidus in mice caused by deleting COOH-terminal tail of aquaporin-2

2007 ◽  
Vol 292 (5) ◽  
pp. F1334-F1344 ◽  
Author(s):  
Peijun P. Shi ◽  
Xiao R. Cao ◽  
Jing Qu ◽  
Ken A. Volk ◽  
Patricia Kirby ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Hormonal Regulation ◽  
Nephrogenic Diabetes Insipidus ◽  
Mdck Cells ◽  
Collecting Duct ◽  
Phosphorylation Site ◽  
Water Channel ◽  
Urine Osmolality ◽  
Functional Expression ◽  
Aquaporin 2

In mammals, the hormonal regulation of water homeostasis is mediated by the aquaporin-2 water channel (Aqp2) of the collecting duct (CD). Vasopressin induces redistribution of Aqp2 from intracellular vesicles to the apical membrane of CD principal cells, accompanied by increased water permeability. Mutations of AQP2 gene in humans cause both recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. In this study, we generated a line of mice with the distal COOH-terminal tail of the Aqp2 deleted ( Aqp2Δ 230), including the protein kinase A phosphorylation site (S256), but still retaining the putative apical localization signal (221–229) at the COOH-terminal. Mice heterozygous for the truncation appear normal. Homozygotes are viable to adulthood, with reduced urine concentrating capacity, increased urine output, decreased urine osmolality, and increased daily water consumption. Desmopressin increased urine osmolality in wild-type mice but had no effect on Aqp2Δ 230/Δ 230 mice. Kidneys from affected mice showed CD and pelvis dilatation and papillary atrophy. By immunohistochemical and immunoblot analyses using antibody against the NH2-terminal region of the protein Aqp2Δ 230/Δ 230 mice had a markedly reduced protein abundance. Expression of the truncated protein in MDCK cells was consistent with a small amount of functional expression but no stimulation. Thus we have generated a mouse model of NDI that may be useful in studying the physiology and potential therapy of this disease.

The occurrence of nephrogenic diabetes insipidus in domestic fowl

1989 ◽  
Vol 256 (4) ◽  
pp. F639-F645 ◽  
Author(s):  
E. J. Braun ◽  
J. N. Stallone
Keyword(s):  
Diabetes Insipidus ◽  
Antidiuretic Hormone ◽  
Domestic Fowl ◽  
Nephrogenic Diabetes Insipidus ◽  
Water Deprivation ◽  
Plasma Osmolality ◽  
Urine Osmolality ◽  
Arginine Vasotocin ◽  
Basal Plasma ◽  
Response To Water

Nephrogenic diabetes insipidus (NDI) results from an inability of the kidney to concentrate the urine. The underlying cause of NDI is the failure of the collecting ducts to respond to antidiuretic hormone, however, the specific tubular defect is not well understood. In the present investigation an apparent case of NDI was studied in a strain of White Leghorn domestic fowl. In this strain, water intake of the males equaled 24.0% (controls 5.4%) of their body mass (BM) per day while that of the females equaled 51.4% (controls 11.7%) of their BM per day. Plasma osmolality (mosmol/kgH2O) of the NDI birds was significantly higher than that of controls (males 319 +/- 1.7 vs. 311 +/- 1.2; females 323 +/- 1.5 vs. 310 +/- 2.2). Urine osmolality of NDI birds was substantially lower than that of controls (males 90 +/- 6.2 vs. 524 +/- 4.0; females 70 +/- 4.7 vs. no value). In response to water deprivation, plasma osmolality of the NDI birds increased more markedly than that of the control animals (males 357 +/- 2.5 vs. 331 +/- 1.2; females 375 +/- 6.0 vs. 348 +/- 1.4 at 48 h of water deprivation). Basal plasma antidiuretic hormone (plasma arginine vasotocin, PAVT) levels in male NDI birds (9.9 +/- 0.7 microU/ml) and in female NDI birds (7.0 +/- 0.5 microU/ml) were nearly sixfold or nearly threefold higher, respectively, than in control birds. In response to water deprivation, PAVT of both NDI and control birds increased to similar levels, although the absolute increases in PAVT levels were substantially less in NDI birds.(ABSTRACT TRUNCATED AT 250 WORDS)

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