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The Turkish Journal of Pediatrics 2022Monosymptomatic nocturnal enuresis (MNE) is defined as involuntary nighttime urination of children over five years of age without any congenital or acquired defect in...
BACKGROUND
Monosymptomatic nocturnal enuresis (MNE) is defined as involuntary nighttime urination of children over five years of age without any congenital or acquired defect in the central nervous system. Many factors, mainly nocturnal polyuria, sleep disorders, decreased bladder capacity, and bladder dysfunctions play a role in the etiology of MNE.
METHODS
Eighty-three children diagnosed with MNE were included in the study. Complete blood cell count, blood biochemistry, renin, and aldosterone levels of all children were obtained. Twenty-four-hour urine samples were collected separately daytime and nighttime and urinary electrolytes were evaluated. Also, 24-hour ambulatory blood pressure monitoring (ABPM) was performed for each patient. The results were evaluated by comparing both enuretic children vs. control group and enuretic children with polyuria vs. without polyuria.
RESULTS
When we compared the enuretic children and the control group in terms of urinary electrolytes, the fractional excretion of sodium (FENa) and fractional excretion of potassium (FEK) values of the enuretic group were higher than the control. The evaluation of the 24-hour ABPM findings revealed no significant difference in terms of the mean arterial pressure (MAP) and diastolic blood pressure (DBP) during the daytime and nighttime measurements. The daytime systolic blood pressure (SBP), however, was significantly lower in the enuretic group. When enuretic children with and without polyuria and the control group were compared, the nighttime, FENa, FEK, as well as nighttime urinary excretion of calcium and protein were significantly higher in enuretic children with polyuria. No difference was detected on the MAP, SBP, or DBP values.
CONCLUSIONS
In conclusion, the nighttime urinary solute excretion of enuretic children was found to be higher and this condition may especially be associated with pathogenesis of nighttime polyuria. In enuretic children, nighttime blood pressure changes were not influential in the etiopathogenesis in all patient groups and multiple mechanisms may play a role in the pathogenesis of enuresis.
Topics: Blood Pressure; Blood Pressure Monitoring, Ambulatory; Child; Electrolytes; Humans; Nocturnal Enuresis; Polyuria
PubMed: 35611421
DOI: 10.24953/turkjped.2020.3343 -
Indian Journal of Psychiatry 2017
PubMed: 29085107
DOI: 10.4103/psychiatry.IndianJPsychiatry_168_17 -
International Journal of Molecular... Nov 2017Under physiological conditions, excessive loss of water through the urine is prevented by the release of the antidiuretic hormone arginine-vasopressin (AVP) from the... (Review)
Review
Under physiological conditions, excessive loss of water through the urine is prevented by the release of the antidiuretic hormone arginine-vasopressin (AVP) from the posterior pituitary. In the kidney, AVP elicits a number of cellular responses, which converge on increasing the osmotic reabsorption of water in the collecting duct. One of the key events triggered by the binding of AVP to its type-2 receptor (AVPR2) is the exocytosis of the water channel aquaporin 2 (AQP2) at the apical membrane the principal cells of the collecting duct. Mutations of either AVPR2 or AQP2 result in a genetic disease known as nephrogenic diabetes insipidus, which is characterized by the lack of responsiveness of the collecting duct to the antidiuretic action of AVP. The affected subject, being incapable of concentrating the urine, presents marked polyuria and compensatory polydipsia and is constantly at risk of severe dehydration. The molecular bases of the disease are fully uncovered, as well as the genetic or clinical tests for a prompt diagnosis of the disease in newborns. A real cure for nephrogenic diabetes insipidus (NDI) is still missing, and the main symptoms of the disease are handled with s continuous supply of water, a restrictive diet, and nonspecific drugs. Unfortunately, the current therapeutic options are limited and only partially beneficial. Further investigation in vitro or using the available animal models of the disease, combined with clinical trials, will eventually lead to the identification of one or more targeted strategies that will improve or replace the current conventional therapy and grant NDI patients a better quality of life. Here we provide an updated overview of the genetic defects causing NDI, the most recent strategies under investigation for rescuing the activity of mutated AVPR2 or AQP2, or for bypassing defective AVPR2 signaling and restoring AQP2 plasma membrane expression.
Topics: Aquaporin 2; Arginine Vasopressin; Diabetes Insipidus, Nephrogenic; Exocytosis; Humans; Mutation; Receptors, Vasopressin
PubMed: 29125546
DOI: 10.3390/ijms18112385 -
Singapore Medical Journal Mar 2023
PubMed: 36926738
DOI: 10.4103/singaporemedj.SMJ-2020-532 -
Research and Reports in Urology 2015Nocturia is the most bothersome lower urinary tract symptom. It has a multifactorial etiology. It had been thought nocturia was a nonspecific symptom of lower urinary... (Review)
Review
Nocturia is the most bothersome lower urinary tract symptom. It has a multifactorial etiology. It had been thought nocturia was a nonspecific symptom of lower urinary system dysfunction, but it has been determined that many diseases, related to different organ systems, might be reasons for this nonspecific symptom. Along with the importance of systemic diseases that cause nocturia, the symptom itself has adverse effects on patients' health and quality of life. There are several studies reporting a direct relationship between nocturia and depression, cognitive dysfunction, mood disturbances, falls, and fractures. For this reason, it is important to treat nocturia both to increase quality of life and to decrease related complications. Treatment opportunities have been under investigation for 20 years. Most of the studies in the literature have reported the results of single-drug medication on nocturia, which may be insufficient for a situation that has such a multifactorial etiology. In this review, we evaluated the success of different treatment combinations on nocturia.
PubMed: 25945323
DOI: 10.2147/RRU.S51140 -
FASEB Journal : Official Publication of... Aug 2018A main feature of Fabry disease is nephropathy, with polyuria an early manifestation; however, the mechanism that underlies polyuria and affected tubules is unknown. To...
A main feature of Fabry disease is nephropathy, with polyuria an early manifestation; however, the mechanism that underlies polyuria and affected tubules is unknown. To increase globotriaosylceramide (Gb3) levels, we previously crossbred asymptomatic Gla mice with transgenic mice that expressed human Gb3 synthase (A4GALT) and generated the GlaTg(CAG-A4GALT) symptomatic Fabry model mice. Additional analyses revealed that these mice exhibit polyuria and renal dysfunction without remarkable glomerular damage. In the present study, we investigated the mechanism of polyuria and renal dysfunction in these mice. Gb3 accumulation was mostly detected in the medulla; medullary thick ascending limbs (mTALs) were the most vacuolated tubules. mTAL cells contained lamellar bodies and had lost their characteristic structure ( i.e., extensive infolding and numerous elongated mitochondria). Decreased expression of the major molecules-Na-K-ATPase, uromodulin, and Na-K-2Cl cotransporter-that are involved in Na reabsorption in mTALs and the associated loss of urine-concentrating ability resulted in progressive water- and salt-loss phenotypes. GlaTg(CAG-A4GALT) mice exhibited fibrosis around mTALs and renal dysfunction. These and other features were consistent with pathologic findings in patients with Fabry disease. Results demonstrate that mTAL dysfunction causes polyuria and renal impairment and contributes to the pathophysiology of Fabry nephropathy.-Maruyama, H., Taguchi, A., Nishikawa, Y., Guili, C., Mikame, M., Nameta, M., Yamaguchi, Y., Ueno, M., Imai, N., Ito, Y., Nakagawa, T., Narita, I., Ishii, S. Medullary thick ascending limb impairment in the GlaTg(CAG-A4GALT) Fabry model mice.
Topics: Animals; Disease Models, Animal; Fabry Disease; Kidney Concentrating Ability; Kidney Diseases; Kidney Medulla; Male; Mice; Mice, Inbred C57BL; Polyuria; Sodium; Sodium-Potassium-Chloride Symporters; Sodium-Potassium-Exchanging ATPase; Trihexosylceramides
PubMed: 29553830
DOI: 10.1096/fj.201701374R -
Frontiers in Pediatrics 2022Bartter syndrome (BS) is a rare tubulopathy that causes polyuria, hypokalemia, hypochloremic metabolic alkalosis, and normotensive hyperreninemic hyperaldosteronism. It... (Review)
Review
Bartter syndrome (BS) is a rare tubulopathy that causes polyuria, hypokalemia, hypochloremic metabolic alkalosis, and normotensive hyperreninemic hyperaldosteronism. It is characterized by locus, clinical, and allelic heterogeneity. Types 1-4 of BS are inherited according to an autosomal recessive pattern, while type 5, which is transient, is X linked. There are specific correlations between the clinical expression and the molecular defect, but since it is a rare disease, such studies are rare. Therapeutic interventions are different, being correlated with types of BS.
PubMed: 35722471
DOI: 10.3389/fped.2022.908655 -
Clinical Journal of the American... Apr 2022The vasopressin V2 receptor antagonist tolvaptan is the only drug that has been proven to be nephroprotective in autosomal dominant polycystic kidney disease (ADPKD).... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
The vasopressin V2 receptor antagonist tolvaptan is the only drug that has been proven to be nephroprotective in autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan also causes polyuria, limiting tolerability. We hypothesized that cotreatment with hydrochlorothiazide or metformin may ameliorate this side effect.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We performed a clinical study and an animal study. In a randomized, controlled, double-blind, crossover trial, we included 13 tolvaptan-treated patients with ADPKD. Patients were treated for three 2-week periods with hydrochlorothiazide, metformin, or placebo in random order. Primary outcome was change in 24-hour urine volume. We also measured GFR and a range of metabolic and kidney injury markers.
RESULTS
Patients (age 45±8 years, 54% women, measured GFR of 55±11 ml/min per 1.73 m) had a baseline urine volume on tolvaptan of 6.9±1.4 L/24 h. Urine volume decreased to 5.1 L/24 h (<0.001) with hydrochlorothiazide and to 5.4 L/24 h (<0.001) on metformin. During hydrochlorothiazide treatment, plasma copeptin (surrogate for vasopressin) decreased, quality of life improved, and several markers of kidney damage and glucose metabolism improved. Metformin did not induce changes in these markers or in quality of life. Given these results, the effect of adding hydrochlorothiazide to tolvaptan was investigated on long-term kidney outcome in an animal experiment. Water intake in tolvaptan-hydrochlorothiazide cotreated mice was 35% lower than in mice treated with tolvaptan only. Combination treatment was superior to "no treatment" on markers of disease progression (kidney weight, =0.003 and cystic index, =0.04) and superior or equal to tolvaptan alone.
CONCLUSIONS
Both metformin and hydrochlorothiazide reduced tolvaptan-caused polyuria in a short-term study. Hydrochlorothiazide also reduced polyuria in a long-term animal model without negatively affecting nephroprotection.
PODCAST
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_03_21_CJN11260821.mp3.
Topics: Adult; Animals; Antidiuretic Hormone Receptor Antagonists; Cross-Over Studies; Female; Humans; Hydrochlorothiazide; Kidney; Male; Metformin; Mice; Middle Aged; Polycystic Kidney, Autosomal Dominant; Polyuria; Quality of Life; Receptors, Vasopressin; Tolvaptan; Treatment Outcome
PubMed: 35314480
DOI: 10.2215/CJN.11260821 -
Nephrology, Dialysis, Transplantation :... Mar 2024The only treatment proven to be renoprotective in autosomal dominant polycystic kidney disease (ADPKD) is a vasopressin V2-receptor antagonist (V2RA). However,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The only treatment proven to be renoprotective in autosomal dominant polycystic kidney disease (ADPKD) is a vasopressin V2-receptor antagonist (V2RA). However, aquaresis-associated side effects limit tolerability. We investigated whether salt and/or protein intake influences urine volume and related endpoints in V2RA-treated ADPKD patients.
METHODS
In this randomized, controlled, double-blind, crossover trial, ADPKD patients treated with maximally tolerated dose of a V2RA were included. While on a low salt and low protein diet, patients were given additional salt and protein to mimic regular intake, which was subsequently replaced by placebo in random order during four 2-week periods. Primary endpoint was change in 24-h urine volume. Secondary endpoints were change in quality of life, measured glomerular filtration rate (mGFR), blood pressure and copeptin level.
RESULTS
Twelve patients (49 ± 8 years, 25.0% male) were included. Baseline salt and protein intake were 10.8 ± 1.3 g/24-h and 1.2 ± 0.2 g/kg/24-h, respectively. During the low salt and low protein treatment periods, intake decreased to 5.8 ± 1.6 g/24-h and 0.8 ± 0.1 g/kg/24-h, respectively. Baseline 24-h urine volume (5.9 ± 1.2 L) decreased to 5.2 ± 1.1 L (-11%, P = .004) on low salt and low protein, and to 5.4 ± 0.9 L (-8%, P = .04) on low salt. Reduction in 24-h urine volume was two times greater in patients with lower urine osmolality (-16% vs -7%). Polyuria quality of life scores improved in concordance with changes in urine volume. mGFR decreased during the low salt and low protein, while mean arterial pressure did not change during study periods. Plasma copeptin decreased significantly during low salt and low protein periods.
CONCLUSION
Lowering dietary salt and protein intake has a minor effect on urine volume in V2RA-treated ADPKD patients. Reduced intake of osmoles decreased copeptin concentrations and might thus increase the renoprotective effect of a V2RA in ADPKD patients.
Topics: Female; Humans; Male; Antidiuretic Hormone Receptor Antagonists; Glomerular Filtration Rate; Kidney; Polycystic Kidney, Autosomal Dominant; Polyuria; Quality of Life; Sodium Chloride, Dietary; Tolvaptan; Double-Blind Method; Cross-Over Studies
PubMed: 37804179
DOI: 10.1093/ndt/gfad218 -
Pediatric Nephrology (Berlin, Germany) Oct 2023Nocturnal enuresis (NE) is a common disease with multiple pathogenic mechanisms. This study aimed to compare levels of metabolites and proteins between wet and dry...
BACKGROUND
Nocturnal enuresis (NE) is a common disease with multiple pathogenic mechanisms. This study aimed to compare levels of metabolites and proteins between wet and dry nights in urine samples from children with monosymptomatic NE (MNE).
METHODS
Ten boys with MNE and nocturnal polyuria (age: 7.6 ± 1.3 years) collected their total nighttime urine production during a wet and a dry night. Untargeted metabolomics and proteomics were performed on the urine samples by liquid chromatography coupled with high-mass accuracy tandem mass spectrometry (LC-MS/MS).
RESULTS
On wet nights, we found reduced urine osmolality (P = 0.025) and increased excretion of urinary potassium and sodium by a factor of, respectively, 2.1 (P = 0.038) and 1.9 (P = 0.19) compared with dry nights. LC-MS identified 59 metabolites and 84 proteins with significantly different levels between wet and dry nights (fold change (FC) < 0.67 or > 1.5, P < 0.05). Some compounds were validated by different methodologies. During wet nights, levels of compounds related to oxidative stress and blood pressure, including adrenalin, were increased. We found reduced levels of aquaporin-2 on wet nights. The FCs in the 59 metabolites were positively correlated to the FCs in the same metabolites identified in urine samples obtained during the evening preceding wet and dry nights.
CONCLUSIONS
Oxidative stress, which in the literature has been associated with nocturia and disturbances in sleep, might be increased during wet nights in children with MNE. We further found evidence of increased sympathetic activity. The mechanisms related to having wet nights in children with MNE seem complex, and both free water and solute handling appear to be important. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Male; Humans; Child; Nocturnal Enuresis; Polyuria; Proteome; Nocturia; Chromatography, Liquid; Tandem Mass Spectrometry; Metabolome; Deamino Arginine Vasopressin
PubMed: 37140712
DOI: 10.1007/s00467-023-05963-5