Urinary aquaporin-2 excretion in nocturnal enuresis

OBJECTIVE: To evaluate the role of the arginine vasopressin (AVP)-aquaporin-2 (AQP-2) axis in the pathogenesis of nocturnal enuresis. STUDY PARTICIPANTS: Twelve children (seven male and five female), aged 11.6+/-4.3 (6.7-15.6) years, suffering from primary monosymptomatic nocturnal enuresis and 12 healthy children, matched for sex and age. Enuretic children were further subdivided into responders and non-responders to treatment with 1-desamino-8-d-AVP (DDAVP). METHODS: Serum concentrations of AVP, and plasma and urine osmolality were measured at night (0100, 0400 and 0700 h), together with nocturnal urinary excretion of AQP-2 (2000-0800 h). Magnetic resonance imaging (MRI) of the pituitary gland was carried out to evaluate the amount of AVP stored in the posthypophysis. RESULTS: Mean AVP serum concentrations were similar in patients and controls. Urinary AQP-2 was also similar in patients and controls, but responders had a significantly lower level of AQP-2 than non-responders (P<0.005). Plasma osmolality was greater in patients than in controls (P<0.001), whereas urinary osmolality was similar in both groups. No difference in the ratio of the signal intensity of the posterior lobe of the hypophysis to that of the pons (AVP content) was found between patients and controls or between responders and non-responders. CONCLUSION: A decreased urinary excretion of AQP-2 is associated with, and seems to have a role in, nocturnal enuresis, at least in some children, and this could also explain why only some of them respond to DDAVP treatment.

Download Full-text

Urinary Aquaporin 2 and Calciuria Correlate with the Severity of Enuresis in Children

Journal of the American Society of Nephrology ◽

10.1681/asn.v11101873 ◽

2000 ◽

Vol 11 (10) ◽

pp. 1873-1881

Author(s):

GIOVANNA VALENTI ◽

ANTONIA LAERA ◽

GIUSEPPE PACE ◽

GABRIELLA ACETO ◽

MARIA L. LOSPALLUTI ◽

...

Keyword(s):

Urinary Excretion ◽

Urine Sample ◽

Western Blotting ◽

Nocturnal Enuresis ◽

Urine Samples ◽

Healthy Children ◽

Nocturnal Polyuria ◽

Aquaporin 2 ◽

Threefold Increase ◽

Absorptive Hypercalciuria

Abstract. This study examined the hypothesis that nocturnal enuresis might be paralleled by aquaporin 2 (AQP2) urinary excretion. Eighty children who experienced nocturnal enuresis were studied and compared with 9 healthy children. The 24-h urine samples were divided into two portions: night collections and day collections. Creatinine equivalents of urine samples from each patient were analyzed by Western blotting. AQP2 levels were semiquantified by densitometric scanning and reported as a ratio between the intensity of the signal in the day urine sample versus the night urine sample (D/N AQP2 ratio). The D/N AQP2 ratio was 0.59 ± 0.11 (n = 9) in healthy children and increased to 1.27 ± 0.24 (n = 10) in a subpopulation of enuretic children who had low nocturnal vasopressin levels. In enuretic children who displayed hypercalciuria and had normal vasopressin levels, the D/N AQP2 ratio was 1.05 ± 0.27 (n = 8). These data indicate that reduced secretion of vasopressin and absorptive hypercalciuria are independently associated with an approximately twofold increase in the urinary D/N AQP2 ratio. When low nocturnal vasopressin levels were associated with hypercalciuria, a nearly threefold increase in the D/N AQP2 ratio was observed (1.67 ± 0.41, n = 11). In addition, in all enuretic patients tested, the urinary D/N AQP2 ratio correlates perfectly with the severity of the disorder (nocturnal polyuria). The findings reported in this article indicate that urinary AQP2 correlates with the severity of enuresis in children.

Download Full-text

NeuroSmog: Determining the Impact of Air Pollution on the Developing Brain: Project Protocol

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph19010310 ◽

2021 ◽

Vol 19 (1) ◽

pp. 310

Author(s):

Iana Markevych ◽

Natasza Orlov ◽

James Grellier ◽

Katarzyna Kaczmarek-Majer ◽

Małgorzata Lipowska ◽

...

Keyword(s):

Airborne Particulate Matter ◽

Population Based ◽

Healthy Children ◽

Monitoring Networks ◽

Neurodevelopmental Outcomes ◽

Psychological Assessments ◽

Hyperactivity Disorder ◽

Magnetic Resonance Imaging Mri ◽

Study Participants ◽

The Impact

Exposure to airborne particulate matter (PM) may affect neurodevelopmental outcomes in children. The mechanisms underlying these relationships are not currently known. We aim to assess whether PM affects the developing brains of schoolchildren in Poland, a country characterized by high levels of PM pollution. Children aged from 10 to 13 years (n = 800) are recruited to participate in this case–control study. Cases (children with attention deficit hyperactivity disorder (ADHD)) are being recruited by field psychologists. Population-based controls are being sampled from schools. The study area comprises 18 towns in southern Poland characterized by wide-ranging levels of PM. Comprehensive psychological assessments are conducted to assess cognitive and social functioning. Participants undergo structural, diffusion-weighted, task, and resting-state magnetic resonance imaging (MRI). PM concentrations are estimated using land use regression models, incorporating information from air monitoring networks, dispersion models, and characteristics of roads and other land cover types. The estimated concentrations will be assigned to the prenatal and postnatal residential and preschool/school addresses of the study participants. We will assess whether long-term exposure to PM affects brain function, structure, and connectivity in healthy children and in those diagnosed with ADHD. This study will provide novel, in-depth understanding of the neurodevelopmental effects of PM pollution.

Download Full-text

Dissociation between urine osmolality and urinary excretion of aquaporin‐2 in healthy volunteers

Nephrology Dialysis Transplantation ◽

10.1093/ndt/15.8.1155 ◽

2000 ◽

Vol 15 (8) ◽

pp. 1155-1161 ◽

Cited By ~ 28

Author(s):

Ruben Baumgarten ◽

Marjolein H. J. van de Pol ◽

Peter M. T. Deen ◽

Carel H. van Os ◽

Jack F. M. Wetzels

Keyword(s):

Urinary Excretion ◽

Healthy Volunteers ◽

Urine Osmolality ◽

Aquaporin 2

Download Full-text

Urinary excretion of aquaporin-2 water channel protein in human and rat.

Journal of the American Society of Nephrology ◽

10.1681/asn.v891357 ◽

1997 ◽

Vol 8 (9) ◽

pp. 1357-1362 ◽

Cited By ~ 1

Author(s):

T Rai ◽

K Sekine ◽

K Kanno ◽

K Hata ◽

M Miura ◽

...

Keyword(s):

Urinary Excretion ◽

Water Channel ◽

Urine Osmolality ◽

Urine Samples ◽

Spot Urine ◽

Aquaporin 2 ◽

Wide Range ◽

Daily Excretion ◽

The Mean ◽

High Concentrations

Previous studies by the authors demonstrated that the response of urinary aquaporin-2 (AQP2) excretion to dDAVP (deamino-8-D-arginine vasopressin) infusion is an index of vasopressin action on the kidney (N Engl J Med 332: 1540-1545, 1995). In the study presented here, the characteristics of urinary excretion of AQP2 were examined further. An RIA suitable for AQP2 in the urine was established. Relatively high concentrations of detergent and bovine serum albumin in the RIA buffer allowed analysis of urine samples with a wide range of concentrations and increased the sensitivity of the assay. AQP2 in the urine existed as a high molecular weight form of approximately 190 kD by HPLC analysis. The mean urinary AQP2 concentration corrected for creatinine in spot urine samples of healthy subjects who voided in the morning was 1081 +/- 699 fmol/mg creatinine (mean +/- SD, n = 208). The amount of daily excretion of AQP2 in the urine was the same in men and women. Urinary AQP2 content was not affected by age of the subjects and showed a positive correlation with urine osmolality. Finally, the fraction of AQP2 excreted in the urine compared with whole kidney content was determined in the rat. Approximately 3% of AQP2 in the kidney was excreted daily, and this fraction did not change when rats were dehydrated for 3 d. These data demonstrate the necessity of establishing well-designed protocols to use urinary AQP2 as a marker of AVP action.

Download Full-text

Sex-Specific Associations of Trimethylamine-N-Oxide and Zonulin with Signs of Depression in Carbohydrate Malabsorbers and Nonmalabsorbers

Disease Markers ◽

10.1155/2020/7897240 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Sophie Meinitzer ◽

Andreas Baranyi ◽

Sandra Holasek ◽

Wolfgang J. Schnedl ◽

Sieglinde Zelzer ◽

...

Keyword(s):

Depressive Symptoms ◽

Beck Depression Inventory ◽

Intestinal Permeability ◽

Serum Concentrations ◽

Carbohydrate Malabsorption ◽

Specific Relationship ◽

Breath Testing ◽

Lactase Gene ◽

Study Participants ◽

Gender Specific

Background. The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. Moreover, carbohydrate malabsorption (CMA) was shown to be associated with signs of depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA. Methods. Serum concentrations of TMAO and zonulin were determined in 115 and 136 individuals with the presence or absence of CMA. All 251 study participants underwent lactase gene C/T-13910 polymorphism genotyping and fructose H2/CH4 breath testing. Additionally, they filled in the Beck Depression Inventory (BDI-II) questionnaire. Results. The median TMAO and zonulin serum concentrations were 2.66 (1.93–4.14) μmol/L and 40.83 (34.73–47.48) ng/mL. Serum TMAO levels were positively correlated with depressive symptoms (P=0.011, ρ=0.160). The strongest correlations were observed in 87 females (P=0.010, ρ=0.274) and 49 males (P=0.027, ρ=0.315) without CMA, whereas 115 patients with CMA showed no significant correlations. Zonulin tended to be negatively correlated with the BDI-II score in 49 males without CMA (P=0.062, ρ=−0.269). Conclusion. This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a gender-specific relationship between the serum TMAO and zonulin concentrations, depression, and CMA.

Download Full-text

Urine and Plasma Osmolality in Patients with Autosomal Dominant Polycystic Kidney Disease: Reliable Indicators of Vasopressin Activity and Disease Prognosis?

American Journal of Nephrology ◽

10.1159/000382081 ◽

2015 ◽

Vol 41 (3) ◽

pp. 248-256 ◽

Cited By ~ 6

Author(s):

Niek F. Casteleijn ◽

Debbie Zittema ◽

Stephan J.L. Bakker ◽

Wendy E. Boertien ◽

Carlo A. Gaillard ◽

...

Keyword(s):

Water Intake ◽

Plasma Osmolality ◽

Urine Osmolality ◽

Kidney Volume ◽

Polycystic Kidney ◽

Estimated Gfr ◽

Total Kidney Volume ◽

Autosomal Dominant Polycystic Kidney ◽

Crude Analysis

Background: Vasopressin plays an essential role in osmoregulation, but has deleterious effects in patients with ADPKD. Increased water intake to suppress vasopressin activity has been suggested as a potential renoprotective strategy. This study investigated whether urine and plasma osmolality can be used as reflection of vasopressin activity in ADPKD patients. Methods: We measured urine and plasma osmolality, plasma copeptin concentration, total kidney volume (TKV, by MRI) and GFR (125I-iothalamate). In addition, change in estimated GFR (eGFR) during follow-up was assessed. Results: Ninety-four patients with ADPKD were included (56 males, age 40 ± 10, mGFR 77 ± 32 ml/min/1.73 m2, TKV 1.55 (0.99-2.40) l. Urine osmolality, plasma osmolality and copeptin concentration were 420 ± 195, 289 ± 7 mOsmol/l and 7.3 (3.2-14.6) pmol/l, respectively. Plasma osmolality was associated with copeptin concentration (R = 0.54, p < 0.001), whereas urine osmolality was not (p = 0.4). In addition, urine osmolality was not associated with TKV (p = 0.3), in contrast to plasma osmolality (R = 0.52, p < 0.001) and copeptin concentration (R = 0.61, p < 0.001). Fifty-five patients were followed for 2.8 ± 0.8 years. Baseline plasma and urine osmolality were not associated with change in eGFR (p = 0.6 and p = 0.3, respectively), whereas baseline copeptin concentration did show an association with change in eGFR, in a crude analysis (St. β = -0.41, p = 0.003) and also after adjustment for age, sex and TKV (St. β = -0.23, p = 0.05). Conclusions: These data suggest that neither urine nor plasma osmolality are valid measures to identify ADPKD patients that may benefit from increasing water intake. Copeptin appears a better alternative for this purpose.

Download Full-text

The majority of natalizumab-treated MS patients have high natalizumab concentrations at time of re-dosing

Multiple Sclerosis Journal ◽

10.1177/1352458517708464 ◽

2017 ◽

Vol 24 (6) ◽

pp. 805-810 ◽

Cited By ~ 16

Author(s):

Zoé LE van Kempen ◽

Cyra E Leurs ◽

Birgit I Witte ◽

Annick de Vries ◽

Mike P Wattjes ◽

...

Keyword(s):

Body Weight ◽

Disease Activity ◽

Brain Magnetic Resonance Imaging ◽

Serum Concentrations ◽

Duration Of Treatment ◽

Treatment Regimens ◽

Trough Serum ◽

Natalizumab Treatment ◽

Magnetic Resonance Imaging Mri ◽

Relapsing Remitting Multiple Sclerosis

Background: Natalizumab is efficacious in the treatment of relapsing-remitting multiple sclerosis. All patients receive the same treatment regimen of 300 mg every 4 weeks, despite differences in pharmacokinetics between individual patients. Objective: To give neurologists insight into natalizumab concentrations at time of re-dosing, we investigated longitudinal natalizumab concentrations in 80 patients in relation to disease activity, with possible influencing factors. Methods: In a prospective observational cohort study, natalizumab trough serum concentrations were measured in 80 patients. Data on demographics, duration of treatment, Expanded Disability Status Scale, clinical exacerbations, brain magnetic resonance imaging (MRI), and body weight were collected. Results: We measured high (≥10 µg/mL) natalizumab trough concentrations in 94% of patients. Intra-individual concentrations were stable. The spread in concentrations was substantial and did not correlate with disease activity. We found a negative association between natalizumab concentration and body weight (β = −0.30, p = 0.010). Interpretation: The majority of patients showed high natalizumab serum concentrations at time of re-dosing. Alternative treatment regimens could lead to more efficient use of natalizumab, but caution is warranted regarding the possibility of recurrence of disease activity. Prospective clinical trials are needed to establish the safety of extended dose intervals in natalizumab treatment.

Download Full-text

Successful rescue of severe hypernatraemia (196 mmol/L) by treatment with hypotonic fluid

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/000456307781646120 ◽

2007 ◽

Vol 44 (5) ◽

pp. 491-494 ◽

Cited By ~ 7

Author(s):

Jinny Jeffery ◽

Ruth M Ayling ◽

Richard J S McGonigle

Keyword(s):

Oral Fluid ◽

Fluid Intake ◽

Case Reports ◽

Pure Water ◽

Plasma Osmolality ◽

Urine Osmolality ◽

Urinary Sodium Excretion ◽

Sodium Concentration ◽

Chronic Renal Impairment ◽

Hypotonic Fluid

Hypernatraemia over 160 mmol/L is considered to be severe. This case reports a patient who developed extreme hypernatraemia with a serum sodium concentration of 196 mmol/L. The patient was known to have chronic renal impairment and was admitted with acute deterioration of renal function secondary to dehydration. This was considered to be secondary to poor oral fluid intake (related to depression) and lithium-induced nephrogenic diabetes insipidus with salt-losing nephropathy. The patient had a high urinary sodium excretion but was also in a pure water losing state as evidenced by an inappropriately low urine osmolality for the plasma osmolality and was successfully treated with hypotonic intravenous fluid and desmopressin.

Download Full-text

Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age-associated defects in urine concentration

AJP Renal Physiology ◽

10.1152/ajprenal.00403.2003 ◽

2004 ◽

Vol 287 (4) ◽

pp. F797-F805 ◽

Cited By ~ 37

Author(s):

Ying Tian ◽

Ryota Serino ◽

Joseph G. Verbalis

Keyword(s):

Collecting Duct ◽

Water Channel ◽

Age Groups ◽

Urine Osmolality ◽

Brown Norway ◽

Water Restriction ◽

Water Excretion ◽

F1 Hybrid ◽

Young Rats ◽

Aquaporin 2

Renal concentrating ability is known to be impaired with aging. The antidiuretic hormone AVP plays an important role in renal water excretion by regulating the membrane insertion and abundance of the water channel aquaporin-2 (AQP2); this effect is primarily mediated via the V2 subtype of the AVP receptor (V2R). This study evaluated the hypothesis that decreased renal sensitivity to AVP, with subsequent altered renal AQP2 expression, contributes to the reduced urinary concentrating ability with aging. Our results show that under baseline conditions, urine osmolality is significantly lower in aged Fischer 344 and Brown-Norway F1 hybrid (F344BN) rats despite equivalent plasma AVP concentrations as in young rats. Levels of kidney V2R mRNA expression and AQP2 abundances were also significantly decreased in aged F344BN rats, as was AQP2 immunostaining in collecting duct cells. In response to moderate water restriction, urine osmolality increased by significantly lesser amounts in aged F344BN rats compared with young rats despite similar increases in plasma AVP levels. Moderate water restriction induced equivalent relative increases in renal AQP2 abundances in all age groups but resulted in significantly lower abundances in total kidney AQP2 protein in aged compared with young F344BN rats. These results therefore demonstrate a functional impairment of renal concentrating ability in aged F344BN rats that is not due to impaired secretion of AVP but rather appears to be related to impaired responsiveness of the kidney to AVP that is secondary, at least in part, to a downregulation of renal V2R expression and AQP2 abundance.

Download Full-text