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

BACKGROUND: 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. METHODS: 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. RESULTS: 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, p = 0.007, and 0.29 vs. 0.53 µmol/24 h, p < 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 (R = 0.37, 0.58, and 0.19, respectively; all p < 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, p < 0.001), whereas no changes in cortisol or total glucocorticoid excretion were observed. CONCLUSIONS: 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.

Osmotic diuresis by SGLT2 inhibition stimulates vasopressin-induced water reabsorption to maintain body fluid volume.

Most of the filtered glucose is reabsorbed in the early proximal tubule by the sodium-glucose cotransporter SGLT2. The glycosuric effect of the SGLT2 inhibitor ipragliflozin is linked to a diuretic and natriuretic effect that activates compensatory increases in fluid and food intake to stabilize body fluid volume (BFV). However, the compensatory mechanisms that are activated on the level of renal tubules remain unclear. Type 2 diabetic Goto-Kakizaki (GK) rats were treated with vehicle or 0.01% (in diet) ipragliflozin with free access to fluid and food. After 8 weeks, GK rats were placed in metabolic cages for 24-hr. Ipragliflozin decreased body weight, serum glucose and systolic blood pressure, and increased fluid and food intake, urinary glucose and Na+ excretion, urine volume, and renal osmolar clearance, as well as urine vasopressin and solute-free water reabsorption (TcH2O). BFV, measured by bioimpedance spectroscopy, and fluid balance were similar among the two groups. Urine vasopressin in ipragliflozin-treated rats was negatively and positively associated with fluid balance and TcH2O, respectively. Ipragliflozin increased the renal membrane protein expression of SGLT2, aquaporin (AQP) 2 phosphorylated at Ser269 and vasopressin V2 receptor. The expression of SGLT1, GLUT2, AQP1, and AQP2 was similar between the groups. In conclusion, the SGLT2 inhibitor ipragliflozin induced a sustained glucosuria, diuresis, and natriuresis, with compensatory increases in fluid intake and vasopressin-induced TcH2O in proportion to the reduced fluid balance to maintain BFV. These results indicate that the osmotic diuresis induced by SGLT2 inhibition stimulates compensatory fluid intake and renal water reabsorption to maintain BFV.

Oxytocin, vasopressin and trust: Associations with aggressive behavior in healthy young males.

Oxytocin enhances trust during social interactions and reduces the tendency for social betrayal. Animal studies have revealed that oxytocin is also an important factor in the establishment and regulation of aggression, for which social interaction is a critical precondition. In humans, however, the effects of oxytocin appear more nuanced and influenced by social context and personality traits. Moreover, the pro-social effects of oxytocin are not mirrored by vasopressin, despite their high chemical similarity. Rather, vasopressin has been associated with an increase of aggressive responses. Therefore, we sought to investigate the association of oxytocin and vasopressin with trust and aggressive behavior. Overnight urinary oxytocin and vasopressin levels were obtained from 62 healthy males (age range: 18-26 years) to compare with trait measures of trust and aggressive behavior. We found a significant interaction of oxytocin and trust on aggression in which low trait measures of trust, in combination with low levels of oxytocin, were associated with a history of aggressive behavior. Notably, we found no significant associations for vasopressin. Although both oxytocin and vasopressin have been shown to be important in the emergence of violent behavior, our study suggests that oxytocin may be particularly modified by affiliative behaviors. These findings provide insights into the neuropsychological influences of oxytocin, and highlights the potential for clinical translation regarding the treatment of patients who exhibit recurrent aggressive behavior.

High Prevalence of Renal Salt Wasting Without Cerebral Disease as Cause of Hyponatremia in General Medical Wards.

BACKGROUND: The approach to hyponatremia is in a state of flux, especially in differentiating syndrome of inappropriate antidiuretic hormone secretion (SIADH) from cerebral-renal salt wasting (RSW) because of diametrically opposite therapeutic goals. Considering RSW can occur without cerebral disease, we determined the prevalence of RSW in the general hospital wards. METHODS: To differentiate SIADH from RSW, we used an algorithm based on fractional excretion (FE) of urate and nonresponse to saline infusions in SIADH as compared to excretion of dilute urines and prompt increase in serum sodium in RSW. RESULTS: Of 62 hyponatremic patients, (A) 17 patients (27%) had SIADH, 11 were nonresponsive to isotonic saline, and 5 normalized a previously high FEurate after correction of hyponatremia; (B) 19 patients (31%) had a reset osmostat based on normal FEurates and spontaneously excreted dilute urines; (C) 24 patients (38%) had RSW, 21 had no clinical evidence of cerebral disease, 19 had saline-induced dilute urines; 2 had undetectable plasma ADH levels when urine was dilute, 10 required 5% dextrose in water to prevent rapid increase in serum sodium, 11 had persistently increased FEurate after correction of hyponatremia and 10 had baseline urinary sodium < 20 mEq/L; (D) 1 patient had Addison disease with a low FEurate and (E) 1 patient (1.6%) had hyponatremia due to hydrochlorothiazide. CONCLUSIONS: Of the 24 patients with RSW, 21 had no cerebral disease, supporting our proposal to change cerebral-renal salt wasting to renal salt wasting. Application of established pathophysiological standards and a new algorithm based on determination of FEurate were superior to the volume approach for determination of urinary sodium when identifying the cause of hyponatremia.

Randomised controlled trial of high versus ad libitum water intake in patients with autosomal dominant polycystic kidney disease: rationale and design of the DRINK feasibility trial.

INTRODUCTION: Vasopressin stimulates cyst growth in autosomal dominant polycystic kidney disease (ADPKD) leading to enlarged kidneys, hypertension and renal failure. Vasopressin receptor blockade slows disease progression. Physiological suppression of vasopressin secretion through high water (HW) intake could achieve a similar effect, necessitating a definitive large-scale trial of HW intake in ADPKD. The objective of the DRINK trial is to answer the key design and feasibility questions required to deliver a successful definitive water intake trial. METHODS AND ANALYSIS: We describe the design of a single-centre, open-label, prospective, randomised controlled trial. The "Determining feasibility of R andomisation to high vs. ad libitum water In take in Polycystic K idney Disease" (DRINK) trial aims to enrol 50 patients with ADPKD, over the age of 16 years with an estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m2. Participants will be randomised 1:1 to HW intake based on an individualised water intake prescription, or to ad libitum (AW) water intake. The HW group will aim for a dilute urine (urine osmolality ≤270 mOsm/kg) as a surrogate marker of vasopressin suppression, and those in the AW group will target more concentrated urine. Participants will have an 8-week treatment period, and will be seen at weeks 0, 2, 4 and 8, undergoing assessments of fluid status, renal function and serum and urine osmolalities. They will receive dietary advice, and self-monitor urine specific gravity and fluid intake. The trial employs smartphone technology to permit home monitoring and remote direct data capture. The primary feasibility end points are recruitment rate and separation between arms in measured urinary osmolality. Key secondary assessments include acceptability, adherence, health-related quality of life, acute effects of HW intake on measured (51Cr-EDTA) and eGFR and ADPKD-related pain. ETHICS AND DISSEMINATION: Ethical approval was awarded by the East of England Essex Research Ethics Committee (16/EE/0026). The results of DRINK will be submitted to peer-reviewed journals, and presented to patients via the PKD Charity. TRIAL REGISTRATION NUMBER: NCT02933268 and ISCRTN16794957.

Urine Concentrating Capacity, Vasopressin and Copeptin in ADPKD and IgA Nephropathy Patients with Renal Impairment.

BACKGROUND: Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients have an impaired urine concentrating capacity. Increased circulating vasopressin (AVP) concentrations are supposed to play a role in the progression of ADPKD. We hypothesized that ADPKD patients have a more severely impaired urine concentrating capacity in comparison to other patients with chronic kidney disease at a similar level of kidney function, with consequently an enhanced AVP response to water deprivation with higher circulating AVP concentrations. METHODS: 15 ADPKD (eGFR<60) patients and 15 age-, sex- and eGFR-matched controls with IgA nephropathy (IgAN), underwent a water deprivation test to determine maximal urine concentrating capacity. Plasma and urine osmolality, urine aquaporin-2 (AQP2) and plasma AVP and copeptin (a surrogate marker for AVP) were measured at baseline and after water deprivation (average 16 hours). In ADPKD patients, height adjusted total kidney volume (hTKV) was measured by MRI. RESULTS: Maximal achieved urine concentration was lower in ADPKD compared to IgAN controls (533±138 vs. 642±148 mOsm/kg, p = 0.046), with particularly a lower maximal achieved urine urea concentration (223±74 vs. 299±72 mmol/L, p = 0.008). After water deprivation, plasma osmolality was similar in both groups although change in plasma osmolality was more profound in ADPKD due to a lower baseline plasma osmolality in comparison to IgAN controls. Copeptin and AVP increased significantly in a similar way in both groups. AVP, copeptin and urine AQP2 were inversely associated with maximal urine concentrating in both groups. CONCLUSIONS: ADPKD patients have a more severely impaired maximal urine concentrating capacity with a lower maximal achieved urine urea concentration in comparison to IgAN controls with similar endogenous copeptin and AVP responses.

Protocol for a prospective, controlled, observational study to evaluate the influence of hypoxia on healthy volunteers and patients with inflammatory bowel disease: the Altitude IBD Study.

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic intestinal disorder, often leading to an impaired quality of life in affected patients. The importance of environmental factors in the pathogenesis of IBD, including their disease-modifying potential, is increasingly recognised. Hypoxia seems to be an important driver of inflammation, as has been reported by our group and others. The aim of the study is to evaluate if hypoxia can alter disease activity of IBD measured by Harvey-Bradshaw Activity Index in Crohn's disease (increase to ≥5 points) and the partial Mayo Score for ulcerative colitis (increase to ≥2 points). To test the effects of hypoxia under standardised conditions, we designed a prospective and controlled investigation in healthy controls and patients with IBD in stable remission. METHODS AND ANALYSIS: This is a prospective, controlled and observational study. Participants undergo a 3-hour exposure to hypoxic conditions simulating an altitude of 4000 metres above sea level (m.a.s.l.) in a hypobaric pressure chamber. Clinical parameters, as well as blood and stool samples and biopsies from the sigmoid colon are collected at subsequent time points. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Kanton Zurich (reference KEK-ZH-number 2013-0284). The results will be published in a peer-reviewed journal and shared with the worldwide medical community. TRIALS REGISTRATION NUMBER: NCT02849821; Pre-results.

Diagnostic value of the water deprivation test in the polyuria-polydipsia syndrome.

OBJECTIVE: Diabetes insipidus (DI) and primary polydipsia (PP) are characterised by polyuria and polydipsia. It is crucial to differentiate between these two disorders since the treatment is different. The aim of this study was to evaluate the diagnostic value of the short and an extended variant of the water deprivation test (WDT) and of measuring urinary vasopressin (AVP) in patients with polyuria and polydipsia. DESIGN: A retrospective, single-centre study based on WDTs performed between 2004 and 2014 including 104 consecutive patients with the polyuria-polydipsia syndrome. During a strict water deprivation, weight, urinary osmolality, urinary vasopressin and specific gravity were collected until one of the following was reached: i) >3% weight reduction, ii) Urinary specific gravity >1.020 or, urinary osmolality >800 mOsm/L, iii) Intolerable adverse symptoms such as excessive thirst. RESULTS: Out of 104 patients (67 women, 37 men), 21 (20%) were diagnosed with DI and 83 (80%) with PP. The median (interquartile range; range) test duration was 14 hours (10-16; 3-36) in patients with DI and 18 hours (14-24; 7-48) in patients with PP (P=0.011). Of those diagnosed with PP, 22 (26%) did not reach urinary specific gravity >1.020 nor urine osmolality >800 mOsm/L. Urine AVP did not overlap between patients with PP and patients with central DI. CONCLUSIONS: The short WDT is of limited value in the diagnostic work-up of polydipsia and polyuria and a partial DI may have been missed in every fourth patient diagnosed with PP. Urinary AVP has excellent potential in discriminating PP from central DI.

Manipulations to the Alcohol and Sodium Content of Beer for Postexercise Rehydration.

The addition of 25 mmol·L(-1) sodium to low alcohol (2.3% ABV) beer has been shown to enhance post exercise fluid retention compared with full strength (4.8% ABV) beer with and without electrolyte modification. This investigation explored the effect of further manipulations to the alcohol and sodium content of beer on fluid restoration following exercise. Twelve male volunteers lost 2.03 ± 0.19% body mass (mean ± SD) using cycling-based exercise. Participants were then randomly allocated a different beer to consume on four separate occasions. Drinks included low alcohol beer with 25 mmol·L-1 of added sodium [LightBeer+25], low alcohol beer with 50 mmol·L(-1) of added sodium [LightBeer+50], midstrength beer (3.5% ABV) [Mid] or midstrength beer with 25 mmol·L(-1) of added sodium [Mid+25]. Total drink volumes in each trial were equivalent to 150% of body mass loss during exercise, consumed over a 1h period. Body mass, urine samples and regulatory hormones were obtained before and 4 hr after beverage consumption. Total urine output was significantly lower in the LightBeer+50 trial (1450 ± 183 ml) compared with the LightBeer+25 (1796 ± 284 ml), Mid+25 (1786 ± 373 ml) and Mid (1986 ± 304 ml) trials (all p < .05). This resulted in significantly higher net body mass following the LightBeer+50 trial (-0.97 ± 0.17 kg) compared with all other beverages (LightBeer+25 (-1.30 ± 0.24 kg), Mid+25 (-1.38 ±0.33 kg) and Mid (-1.58 ±0.29 kg), all p < .05). No significant changes to aldosterone or vasopressin were associated with different drink treatments. The electrolyte concentration of low alcohol beer appears to have more significant impact on post exercise fluid retention than small changes in alcohol content.

Social peptides: measuring urinary oxytocin and vasopressin in a home field study of older adults at risk for dehydration.

OBJECTIVES: We present the novel urine collection method used during in-home interviews of a large population representative of older adults in the United States (aged 62-91, the National Social Life, Health and Aging Project). We also present a novel assay method for accurately measuring urinary peptides oxytocin (OT) and vasopressin (AVP), hormones that regulate social behaviors, stress, and kidney function. METHOD: Respondents in a randomized substudy (N = 1,882) used airtight containers to provide urine specimens that were aliquoted, stored under frozen refrigerant packs and mailed overnight for frozen storage (-80 °C). Assays for OT, AVP, and creatinine, including freeze-thaw cycles, were refined and validated. Weighted values estimated levels in the older U.S. population. RESULTS: Older adults had lower OT, but higher AVP, without the marked gender differences seen in young adults. Mild dehydration, indicated by creatinine, specific gravity, acidity, and AVP, produced concentrated urine that interfered with the OT assay, yielding falsely high values (18% of OT). Creatinine levels (≥ 1.4 mg/ml) identified such specimens that were diluted to solve the problem. In contrast, the standard AVP assay was unaffected (97% interpretable) and urine acidity predicted specimens with low OT concentrations. OT and AVP assays tolerated 2 freeze-thaw cycles, making this protocol useful in a variety of field conditions. DISCUSSION: These novel protocols yielded interpretable urinary OT and AVP values, with sufficient variation for analyzing their social and physiological associations. The problem of mild dehydration is also likely common in animal field studies, which may also benefit from these collection and assay protocols.

The impact of obstructive sleep apnea syndrome on nocturnal urine production in older men with nocturia.

OBJECTIVE: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on night-time secretion of brain natriuretic peptide (BNP) and antidiuretic hormone (ADH) in older men with nocturia accompanied by nocturnal polyuria. MATERIALS AND METHODS: One hundred six men with nocturia aged ≥ 60 years underwent full-night polysomnography to determine whether they had OSAS. Blood count, standard chemistry panel, BNP, urinary ADH, urinary creatinine (u-Cre), and urinary osmolarity were measured at 6:00 AM, and a frequency volume chart was recorded on the same day that polysomnography was performed. RESULTS: We evaluated 83 patients after excluding 18 with mild OSAS and 5 with nocturnal polyuria index <0.35. Participants with OSAS had higher apnea-hypopnea index (P < .0001) than those without OSAS. Body mass index and systolic blood pressure were higher in OSAS patients than those in the control group. BNP was higher in the OSAS patients than in the control patients (48.6 ± 41.4 vs 30.7 ± 31.5; P = .0006). On urinalysis, OSAS patients showed higher urinary sodium and u-Cre secretion than controls (24.7 ± 11.3 vs 16.2 ± 5.1; P <.0001). Urine osmolarity was also higher in OSAS patients than in the control patients (616 ± 172 vs 516 ± 174; P = .0285). There was no significant difference in urinary ADH and u-Cre (6.7 ± 10.4 vs 6.8 ± 7.8; P = .3617) between the 2 groups. CONCLUSION: Our results indicated that older men with nocturnal polyuria and OSAS did not compensate their fluid imbalance presented with decreased secretion of ADH but increased BNP level.

Effect of chronic inhibition of converting enzyme on renal handling of salt and water: a study on a pediatric population.

BACKGROUND/AIMS: The effect of angiotensin-converting enzyme inhibition (ACEi) is amply documented in several pathological conditions. However, there are few reports about the effect of chronic ACEi on salt and water balance.The present work evaluates the effect of chronic ACEi on salt and water balance in a population of children receiving enalaprilchronically in order to reduce albuminuria elicited by auremic hemolytic syndrome. METHODS: Nine children aged from 9 to 19 years with normal glomerular filtration rate, normotension and with urinary concentration capacity preserved were treated with enalapril with doses ranging between 0.1 and 0.30 mg/kg/day. Diuresis, urinary absolute and fractional excretion of Na(+), K(+) and urea, creatinine clearance,osmolal clearance and tubular water reabsorption were measured under three experimental procedures: (1)with free access to water; (2) with a water load and (3) with water restriction. In the last group urinary antidiuretic hormone(ADH) was measured. These tests were performed ina paired way, just before starting ACEi treatment and after 6 months of enalapril treatment. RESULTS: Enalapril treatment diminished the urinary concentration capacity without affecting Na(+) and K(+) urinary excretion. Creatinine clearance was not modified except in the condition of water load where a fall in it was found after ACEi. ADH increased after enalapril treatment in children under water restriction. CONCLUSION: In these children chronic ACEi decreases urinary concentration capacity.

Determination of Vasopressin and Desmopressin in urine by means of liquid chromatography coupled to quadrupole time-of-flight mass spectrometry for doping control purposes.

The anti-diuretic neurohypophysial hormone Vasopressin (Vp) and its synthetic analogue Desmopressin (Dp, 1-desamino-vasopressin) have received considerable attention from doping control authorities due to their impact on physiological blood parameters. Accordingly, the illicit use of Desmopressin in elite sport is sanctioned by the World Anti-Doping Agency (WADA) and the drug is classified as masking agent. Vp and Dp are small (8-9 amino acids) peptides administered orally as well as intranasally. Within the present study a method to determine Dp and Vp in urinary doping control samples by means of liquid chromatography coupled to quadrupole high resolution time-of-flight mass spectrometry was developed. After addition of Lys-Vasopressin as internal standard and efficient sample clean up with a mixed mode solid phase extraction (weak cation exchange), the samples were directly injected into the LC-MS system. The method was validated considering the parameters specificity, linearity, recovery (80-100%), accuracy, robustness, limit of detection/quantification (20/50 pg mL(-1)), precision (inter/intra-day<10%), ion suppression and stability. The analysis of administration study urine samples collected after a single intranasal or oral application of Dp yielded in detection windows for the unchanged target analyte for up to 20 h at concentrations between 50 and 600 pg mL(-1). Endogenous Vp was detected in concentrations of approximately 20-200 pg mL(-1) in spontaneous urine samples obtained from healthy volunteers. The general requirements of the developed method provide the characteristics for an easy transfer to other anti-doping laboratories and support closing another potential gap for cheating athletes.

Upregulation of calbindin D28k in the late distal tubules in the potassium-loaded adrenalectomized mouse kidney.

BACKGROUND: The calcium (Ca)-activated potassium (K) channel is an alternative K-secretory pathway in the apical membranes of the distal nephrons of adrenalectomized (ADX) animals. As a potential approach for estimating intracellular Ca(2+) increase, we investigated normal and ADX mice to determine whether dietary K intake would stimulate the expression of the calbindin D28k protein, a cytosolic Ca(2+)-binding protein, along the distal nephron consisting of the early and late portions of the distal convoluted tubule (DCT1 and DCT2, respectively), the CNT, and CCD. METHODS: ADX mice received a control diet plus either 0.3% NaCl solution (C) or a 0.3% NaCl plus 3% KCl solution (HK) for 7 days before the experiment. RESULTS: The mean plasma K concentration and pH were significantly (P < 0.001) higher (7.9 ± 0.3 mEq/l) and lower (7.28 ± 0.02) in the K-loaded ADX mice than in the control ADX mice. The mean urinary K excretion (mEq/day) and urine flow (ml/day) increased significantly (P < 0.0001) from 0.47 ± 0.07 (C) to 4.80 ± 0.57 (HK) and from 1.1 ± 0.2 (C) to 8.8 ± 1.0 (HK). Urinary Ca excretion significantly (P < 0.005 and P < 0.05, respectively) increased in K-loaded normal and ADX mice compared with control normal and ADX mice. Immunofluorescence studies revealed that the relative staining of calbindin was 167.0 ± 15.4%, 291.3 ± 13.8%, and 206.3 ± 11.3% for DCT1, DCT2/CNT, and CCD of normal control mice, respectively. These values increased significantly (P < 0.0001) only in DCT2/CNT (574.8 ± 42%) of the K-loaded ADX mice. CONCLUSION: Upregulation of calbindin in the late distal tubule suggests that Ca(2+)-dependent K transport may function as an alternative mechanism for urinary K excretion in ADX mice.

Familial nephrogenic syndrome of inappropriate antidiuresis: dissociation between aquaporin-2 and vasopressin excretion.

CONTEXT: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD), the X-linked disease resulting from activating mutation of the vasopressin V2 receptor gene (AVPR2), is a recently described condition causative of episodes of hyponatremia in boys and male and female adults. OBJECTIVE: The objective of the study was the pathophysiological characterization of NSIAD. DESIGN: A family with NSIAD was identified and investigated for hyponatremic episodes and degrees of urine dilution defects. For the first time, the impact of the mutated V2R on aquaporin 2 (AQP2) excretion is reported. SETTING: The study was conducted at a referral center. PATIENTS: Five patients of seven carriers (two young brothers and their mother and her two sisters) were investigated together with age-matched controls. INTERVENTIONS: There were no interventions. RESULTS: In NSIAD patients, urinary AQP2 excretion occurred independently of concomitant vasopressin excretion and strongly correlated with urine osmolality, confirming direct AQP2 involvement in urine concentration. Water loading was followed by a very slow and incomplete elimination in the asymptomatic hemizygous boy with no suppression of AQP2 excretion and a delayed elimination in the heterozygous women because of an incomplete suppression of AQP2, and it induced hyponatremia in all NSIAD patients. Two hemizygous carriers presented with severe hyponatremia-induced seizures, and the repetition in one of them led to mental retardation. CONCLUSIONS: Hyponatremia was a constant and characteristic aspect of the abnormal response to even mild water-loading tests in an asymptomatic hemizygous child as well as heterozygous adults. We confirm the phenotypic variability of NSIAD, a disease that should be regarded in pediatric intensive care units in presence of severe and/or recurrent hyponatremia, and also in adults, because carriers are prone to hyponatremia.

[Osmoregulating effect of vasopressin with prolonged action on Brattleboro rats with hypothalamic diabetes insipidus].

The particularities of urine osmotic concentration depending on hormonal background of vasopressin were studied in rats. It was found that WAG and Brattleboro lines of rats characterized respectively by normal level and absence of endogenous vasopressin, possess interline correlation of urine osmolality (p = 0.86) in various conditions between the extreme hydrating and dehydratation. Concentrating level of WAG rats varies from 747 +/- 94 to 2936 +/- 128 mOsm/kg, but that of Brattleboro rats changes more within the 160 +/- 9 being twice lower as isotonicity to 1305 +/- 142 mOcm/kg. Urine concentrating goes up to 1391 +/- 76 mOcm/kg in Brattleboro rats already on the day of the action of exogenous vasopressin secreted from ALZET minipump, however, in spite of constant work of this minipump during 4 hrs a week, further increasing of urine osmolality was not observed in Brattleboro rats.