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The elucidation of the underlying cause of polyuria-polydipsia syndrome (PPS) is a challenging-especially in the differentiation of partial defects of arginine vasopressin (AVP) secretion or action from primary polydipsia. The water deprivation test has been utilized for many decades, and its application in the paediatric population has been applied using parameters predominantly established in adult cohorts. In more recent times, the development of automated commercial assays for copeptin, a surrogate marker for AVP, has represented a significant advancement in the diagnostic approach to PPS. Measurement of copeptin concentrations has major advantages and has essentially superseded measurement of AVP in diagnostic protocols for PPS. Additionally, stimulated-copeptin protocols utilizing hypertonic saline infusion, arginine, and glucagon have been investigated, and are promising. However, further studies are required in the population-incorporating the differences in physiological regulation of water homeostasis, and safety requirements-before there is widespread adoption into clinical practice.
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OBJECTIVE: Plasma copeptin is a relatively new biomarker for evaluation of arginine vasopressin (AVP) secretion. The aim of this study was to test the diagnostic performance of copeptin in patients with polyuria-polydipsia syndrome. DESIGN, PATIENTS AND MEASUREMENTS: This was a prospective study where 88 patients with polyuria-polydipsia syndrome were evaluated with a water deprivation test (WDT). Weight, urine osmolality, urine specific gravity, and plasma copeptin were collected at baseline, after 8 h, and at termination of the WDT when one of the following had been reached: (i) >3% weight reduction, (ii) urine specific gravity >1.017 or urine osmolality >600 mOsm/kg, or (iii) intolerable adverse symptoms. RESULTS: Of 88 patients (57 women), 21 (24%) were diagnosed with central diabetes insipidus (cDI), 5 (6%) with nephrogenic DI (nDI), and 62 (71%) with primary polydipsia (PP). Median (interquartile range) copeptin at baseline was 1.7 (1.4-2.5) pmol/L in cDI, 22 (18-65) pmol/L in nDI, and 2.7 (2-4) pmol/L in PP. After 8 h of WDT, the highest copeptin in patients with cDI was 4.0 pmol/L. In patients with PP: (i) 41 had urine osmolality <600 mOsm/kg, 7 (17%) of these had copeptin >4.0 pmol/L, (ii) 21 had urine osmolality ≥600 mOsm/kg, 14 (67%) of these had copeptin >4.0 pmol/L. CONCLUSIONS: Copeptin >4.0 pmol/L after an overnight WDT can be used to rule out cDI and copeptin ≥21 pmol/L at baseline to diagnose nDI. The diagnostic performance of copeptin in the context of the WDT is otherwise limited in the diagnostic work-up of patients with polyuria-polydipsia syndrome.
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Glicopeptídeos , Polidipsia , Poliúria , Humanos , Glicopeptídeos/sangue , Feminino , Masculino , Estudos Prospectivos , Adulto , Poliúria/diagnóstico , Poliúria/sangue , Poliúria/urina , Polidipsia/diagnóstico , Polidipsia/sangue , Pessoa de Meia-Idade , Biomarcadores/sangue , Concentração Osmolar , Adulto Jovem , Privação de ÁguaRESUMO
Arginine vasopressin (AVP) plays a main role in maintaining the homeostasis of fluid balance and vascular tone and in regulating the endocrine stress response in response to osmotic, hemodynamic and stress stimuli. However, the difficulty in measuring AVP limits its clinical application. Copeptin, the C-terminal part of the AVP precursor, is released in an equimolar concentration mode with AVP from the pituitary but is more stable and simple to measure. Therefore, copeptin has emerged as a promising surrogate marker of AVP with excellent potential for the diagnosis, differentiation and prognosis of various diseases in recent decades. However, its application requires further validation, especially in the pediatric population. This review focuses on the clinical value of copeptin in different pediatric diseases and the prospects for its application as a potential biomarker.
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PURPOSE: Evidence on the efficacy of desmopressin in nocturia in patients with neurological diseases is still very limited except for multiple sclerosis (MS). Our aim was to evaluate the efficacy and safety of desmopressin treatment on nocturia in patients with underlying neurological diseases. METHODS: Studies were identified by electronic search of PubMed, Embase, Cochrane, CINAHL, and Google Scholar databases. Studies were considered if they provided information on the effectiveness and safety of desmopressin (1-desamino-8-d-arginine vasopressin, or DDAVP) in the treatment of nocturia and their participants had acquired neurological pathology. Two researchers independently extracted the articles using specified datasets, such as quality-of-study indicators. Statistical meta-analysis was carried out using Review Manager (RevMan) 5.4 statistical software (Cochrane Collaboration). RESULTS: Of a total of 1042 articles in the initial search, 14 studies were included. Most of the published papers were related to MS (n = 7), two were on spinal cord injury, and other conditions were neural tube defect, myelodysplasia, Parkinson's disease, stroke, and multiple system atrophy. Overall, a total of 200 patients (mostly females) were enrolled. Thirteen studies evaluated the intranasal formulation of desmopressin and one study evaluated oral desmopressin. A significant decrease in nocturia episodes was reported in seven studies evaluating this topic. An increase in the maximum hours of uninterrupted sleep was reported in the three studies in which this outcome was assessed. A significant reduction in the volume of nocturnal incontinence was found in one study. Three studies were eligible to include in the meta-analysis. The results showed that desmopressin compared to placebo, significantly reduced nighttime urination (mean difference: -0.75, 95% CI: -1.10 to -0.41; p < 0.00001). The rate of adverse events ranged from 0% to 68.42%. The critical appraisal results for all trials showed that most of the studies had low or moderate quality. CONCLUSIONS: Our results emphasized desmopressin's safety and efficacy in reducing nocturia episodes, with transient adverse effects on neurological patients. However, the data were achieved from low or medium-quality trials, and further well-designed randomized controlled trials are needed.
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Esclerose Múltipla , Noctúria , Feminino , Humanos , Masculino , Noctúria/tratamento farmacológico , Noctúria/etiologia , Desamino Arginina Vasopressina/efeitos adversos , Poliúria , Antidiuréticos/efeitos adversos , Resultado do Tratamento , Esclerose Múltipla/tratamento farmacológicoRESUMO
AIMS: To investigate changes in subjective and objective sleep quality after desmopressin administration in patients with nocturia due to nocturnal polyuria (NP) using electroencephalography (EEG) and the Pittsburgh sleep quality index (PSQI). METHODS: Twenty male patients (≥65 years old) with NP participated in this study. The inclusion criteria were nocturnal frequency ≥ 2, NP index (NPi) ≥ 0.33, first uninterrupted sleep period (FUSP) ≤ 2.5 h, serum sodium concentration ≥ 135 mEq/L, and estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2. Participants were given 50 µg of desmopressin to be taken orally once daily before bed. The primary endpoint was the change in the duration of slow-wave sleep (nonrapid eye movement sleep stages 3 and 4), as evaluated by EEG 28 days from the baseline. The visual analog scale (VAS) was used as an additional indicator of sleep quality. RESULTS: Analysis of data from 15 participants (median age: 74.0 [70.5, 76.0] years) revealed that from before to after desmopressin administration, significant decreases occurred in the median nocturnal frequency (3.0 [2.0, 4.0] to 1.5 [1.0, 2.0]) and NPi (0.445 [0.380, 0.475] to 0.360 [0.250, 0.430]). Furthermore, FUSP was significantly prolonged from 120.0 (94.0, 150.0) min to 210.0 (203.8, 311.3) min. Although the VAS scores improved, slow-wave sleep duration and the PSQI global score showed no significant differences (68.50 [47.50, 75.50] and 48.00 [38.00, 66.50]; 5.0 [5.0, 10.0] and 7.0 [5.0, 9.0] min, respectively). CONCLUSION: Oral administration of 50 µg desmopressin improved nocturnal frequency and FUSP in older individuals with NP but did not significantly enhance sleep quality. In older adults, decreased nighttime urinary frequency may enhance quality of life; however, its influence on objective sleep quality may be limited.
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Desamino Arginina Vasopressina , Eletroencefalografia , Noctúria , Poliúria , Sono de Ondas Lentas , Humanos , Desamino Arginina Vasopressina/administração & dosagem , Desamino Arginina Vasopressina/farmacologia , Masculino , Idoso , Poliúria/tratamento farmacológico , Poliúria/fisiopatologia , Noctúria/tratamento farmacológico , Noctúria/fisiopatologia , Sono de Ondas Lentas/efeitos dos fármacos , Administração Oral , Antidiuréticos/administração & dosagem , Antidiuréticos/farmacologia , Resultado do Tratamento , Qualidade do SonoRESUMO
INTRODUCTION: Nocturia is a complex and multifactorial condition, associated with several genitourinary abnormalities as well as a host of conditions beyond the urinary tract, and thus often poses a significant diagnostic challenge in real-world practice. Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications, the so-called "Sleep C.A.L.M." factors, are five common causes of nocturia requiring judicious evaluation according to current consensus guidelines. This study aims to assess the prevalence of the Sleep C.A.L.M. factors in a nocturia clinical population. METHODS: Retrospective analysis of frequency-volume charts from men with ≥2 nocturnal voids as well as concurrent demographic, clinical, and medical history data to identify patients with each of the Sleep C.A.L.M. FACTORS: Comorbidities and medications were classified as a single group. RESULTS: A total of 213 subjects met the criteria for inclusion (median age 68.0 [63.5-75.5] years). The prevalence of 1) sleep disorders, 2) comorbidities and/or medication use, 3) actions (i.e., modifiable behaviors/lifestyle factors), and 4) lower urinary tract dysfunction was 31%, 31%, 19%, and 41%, respectively. Among included participants, 73% were found to have at least 1 Sleep C.A.L.M. factor, and 33% had multiple Sleep C.A.L.M. FACTORS: Results were similar upon stratification by age and nocturnal polyuria status. CONCLUSIONS: The Sleep C.A.L.M. factors are highly common among nocturia patients in the clinical urology setting. Although many of these factors are strongly associated with advanced age in community-based nocturia study samples, they appear common even among younger men in a nocturia patient population; the differential effect of age and individual Sleep C.A.L.M. factors on nocturia pathophysiology requires further investigation.
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Noctúria , Transtornos do Sono-Vigília , Humanos , Noctúria/epidemiologia , Noctúria/fisiopatologia , Noctúria/diagnóstico , Masculino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Prevalência , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/diagnóstico , Veteranos , Comorbidade , Fatores de Risco , SonoRESUMO
Polyuria-polydipsia syndrome is a frequent symptom in pediatrics, primarily attributed to diabetes mellitus. In the context of diabetes insipidus, this syndrome can stem from central or nephrogenic factors. Sjögren's syndrome, an uncommon autoimmune disease in children, can affect multiple organs. Kidney involvement as described in adults is usually related to glomerular or tubular impairment, often linked to distal tubular acidosis. As a kidney involvement during childhood, Sjögren's syndrome has rarely been reported. Hereby, we present the case of Sjögren's syndrome revealed by polyuria-polydipsia syndrome in a 10-year-old boy.
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Doenças Autoimunes , Diabetes Insípido , Síndrome de Sjogren , Criança , Humanos , Masculino , Diabetes Insípido/complicações , Diabetes Insípido/diagnóstico , Polidipsia/diagnóstico , Polidipsia/etiologia , Poliúria/diagnóstico , Poliúria/etiologia , Síndrome de Sjogren/diagnósticoRESUMO
BACKGROUND: The management of posterior urethral valve (PUV) in neonates requires close monitoring in the intensive care unit because of the risk of post-obstructive diuresis (POD). Our aim was to describe the incidence and factors associated with POD in newborns treated for PUV. METHODS: Retrospective analysis of the medical records of all neonates who underwent surgical intervention for PUV in our neonatal intensive care unit between January 2014 and April 2021. RESULTS: Of the 40 patients included, 15 (37.5%) had POD defined by urine output > 6 ml.kg-1.h-1 during the first 24 h following urinary tract obstruction relief. At prenatal ultrasound examinations, oligohydramnios was more common in the group with POD than in the group without (53.3% vs. 8%, p = 0.002). Preterm birth was more frequent in neonates with POD (66.7% vs. 8%; p < 0.001). Median serum creatinine (212 [137-246] vs. 95 [77-125] µmol.l-1; p < 0.001) and urea (8.5 [5.2-12.2] vs. 4.1 [3.5-4.7] mmol.l-1; p < 0.001) concentrations on the day of obstruction relief were significantly higher in the group with POD than in the group without. After adjustment for prematurity, logistic regression models confirmed correlation between the occurrence of POD and the severity of the consequences of urethral obstruction (i.e., oligohydramnios and serum creatinine levels; ß = 2.90 [0.88; 5.36], p = 0.013 and ß = 0.014 [0.003; 0.031], p = 0.034, respectively). CONCLUSIONS: In neonates, POD is common after the relief of PUV-related obstruction. Our findings may help to identify patients at highest risk. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Oligo-Hidrâmnio , Nascimento Prematuro , Obstrução Uretral , Sistema Urinário , Gravidez , Feminino , Humanos , Recém-Nascido , Estudos Retrospectivos , Creatinina , Obstrução Uretral/etiologia , Obstrução Uretral/cirurgia , Diurese , Uretra/cirurgiaRESUMO
INTRODUCTION AND HYPOTHESIS: The aim of this review is to discuss the link between menopause and nocturia and to give an overview of the increasing prevalence, risk factors, causative factors, treatment needs and options for nocturia in peri-menopausal women. METHODS: This opinion article is a narrative review based on the expertise and consensus of a variety of key opinion leaders, in combination with an extensive literature review. This literature search included a thorough analysis of potential publications on both the PubMed Database and the Web of Science and was conducted between November 2022 and December 2022. The following key words were used "nocturia" and "menopause" or "nocturnal frequency and menopause." Moreover, key words including "incidence," "prevalence," "insomnia," "estrogen therapy," "metabolic syndrome," and "hot flushes" were used in combination with the aforementioned key words. Last, the reference lists of articles obtained were screened for other relevant literature. RESULTS: The perimenopause can be a trigger for inducing nocturia. Typically, obesity, body mass index (BMI), and waist circumference are risk factors for developing peri-menopausal nocturia. Presumably the development of peri-menopausal nocturia is multifactorial, with interplay among bladder, sleep, and kidney problems due to estrogen depletion after the menopause. First, impaired stimulation of estrogen receptors in the urogenital region leads to vaginal atrophy and reduced bladder capacity. Moreover, menopause is associated with an increased incidence of overactive bladder syndrome. Second, estrogen deficiency can induce salt and water diuresis through blunted circadian rhythms for the secretion of antidiuretic hormone and the activation of the renin-angiotensin-aldosterone system. Additionally, an increased incidence of sleep disorders, including vasomotor symptoms and obstructive sleep apnea signs, is observed. Oral dryness and a consequent higher fluid intake are common peri-menopausal symptoms. Higher insulin resistance and a higher risk of cardiovascular diseases may provoke nocturia. Given the impact of nocturia on general health and quality of life, bothersome nocturia should be treated. Initially, behavioral therapy should be advised. If these modifications are inadequate, specific treatment should be proposed. Systemic hormone replacement is found to have a beneficial effect on nocturia, without influencing sodium and water clearance in patients with nocturnal polyuria. It is presumed that the improvement in nocturia from hormonal treatment is due to an improvement in sleep disorders.
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Menopausa , Noctúria , Humanos , Noctúria/epidemiologia , Noctúria/etiologia , Feminino , Menopausa/fisiologia , Fatores de Risco , Pessoa de Meia-Idade , Prevalência , Incidência , Terapia de Reposição de Estrogênios , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Obesidade/complicações , FogachosRESUMO
BACKGROUND: Copeptin stimulation tests can be used in the differential diagnosis of polyuria polydipsia syndrome. Current stimulation methods rely on intravenous or subcutaneous administration. Oral stimulus can further simplify the diagnostic approach. The levodopa stimulation test is widely used in the evaluation of growth hormone deficiency (GHD), and the dopamine pathway was reported to be associated with arginine vasopressin secretion. The study aimed to investigate the effect of oral levodopa on copeptin secretion. METHODS: The study was a prospective observational single-center cohort study. Patients < 18 years old with short stature and no symptoms of polyuria or polydipsia undergoing levodopa stimulation test for suspected GHD were recruited from May 2023 to Nov 2023. Copeptin and growth hormone (GH) were measured at 0, 30, 60, 90, and 120min in the levodopa test. The insulin tolerance test with copeptin and GH measured at the same time points was conducted in part of patients. RESULTS: Forty-four participants were included in the final analysis. In the levodopa stimulation test, the median (interquartile range, IQR) copeptin concentration increased from 5.20 (3.51, 8.25) pmol/L to maximum 19.36 (8.97, 108.08) pmol/L (P < 0.001), 3.94 (1.41, 13.88) times of the baseline (P < 0.001). Compared with insulin tolerance test, peak copeptin in the levodopa test was significantly higher (34.61 (13.67, 98.96) vs 8.88 (7.14, 15.42) pmol/L, P = 0.009). Higher copeptin was associated with larger dose of levodopa. CONCLUSIONS: Oral levodopa could be used to stimulate copeptin.
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AIM: To investigate the role of autonomic nervous system in subpopulations of children with enuresis. METHODS: We included 35 children with enuresis, divided in children with (17) and without nocturnal polyuria (18) and 43 healthy controls. For all participants hormones and neurotransmitters were measured. Patients and controls wore a sleep tracker device and children with enuresis underwent a 24 h blood pressure monitoring, nocturnal urine output measurement and uroflowmetry. RESULTS: Children with enuresis had lower than controls copeptin and aldosterone, with the latter being more prominent in patients without nocturnal polyuria. Dopamine was lower in patients without nocturnal polyuria compared with patients with nocturnal polyuria. Children without polyuria experienced episodes only during NREM sleep, whereas in children with polyuria episodes occurred in both REM and NREM sleep. Children with enuresis experienced a non-dipping phenomenon during sleep which was more prominent in the group without polyuria. CONCLUSION: In patients with nocturnal polyuria, nocturnal enuresis is associated with sympathetic hyperactivity which results in pressure polyuria and significantly lower systolic dipping during sleep. On the contrary, in children without nocturnal polyuria, it is mostly associated with bladder overactivity due to parasympathetic overstimulation as demonstrated by the NREM-related enuretic episodes and the lower aldosterone and dopamine levels.
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OBJECTIVES: Desmopressin improves nocturia frequency; however, reports on its long-term efficacy and safety are few, and concerns regarding its effect on body composition exist. We thus investigated the efficacy and safety of long-term desmopressin administration and its effect on body composition. METHODS: This retrospective study, conducted at Chikugo City Hospital between August 2020 and December 2022, involved 133 men (mean age, 77.7 years) with nocturnal and persistent nocturia, who were administered an initial dose of 50 µg desmopressin. Efficacy endpoints included nocturnal urinary frequency, nocturnal urinary volume, hours of undisturbed sleep, nocturnal polyuria index, initial nocturnal urinary volume, and daily urinary frequency in a frequency-volume chart (3 days), before treatment and at 1, 4, 12, 24, and 52 weeks after desmopressin administration. Additionally, the effects of desmopressin on body composition were examined, including blood-brain natriuretic peptide and a chest radiography, before and 52 weeks after administration. RESULTS: Treatment improved most efficacy endpoint evaluation parameters. Around 87.6% of patients showed improved symptoms after 52 weeks compared with those before treatment (score ≤ 3). The blood-brain natriuretic peptide level rose; however, cardiothoracic ratio was unchanged. CONCLUSION: Long-term administration of desmopressin is thus effective and safe in older people with nocturnal polyuria, with little effect on body composition.
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OBJECTIVES: Nocturnal polyuria (NP) is one of the causes of nocturia that impairs quality of life. It is necessary to consider that NP is latent when the initial treatment for nocturia is unsatisfactory. Therefore, it is important to establish a treatment for NP based on the pathophysiology. We have previously reported the relationship between NP and fluctuation in blood pressure. The present study aimed to investigate the association between NP and 24-h blood pressure fluctuations in a multicenter prospective study. METHODS: This study included male patients with lower urinary tract symptoms. We categorized the patients into the nonnocturnal polyuria (non-NP) group (≤0.33) and the NP group (>0.33) based on the nocturnal polyuria index from the frequency volume chart. We measured the 24-h diurnal blood pressure and compared the two groups. RESULTS: Among 90 patients, 46 in the non-NP group and 44 in the NP group were included. There was no significant difference in the systolic and diastolic blood pressure during waking time between the two groups; however, the degree of systolic blood pressure reduction during sleep time in the NP group was significantly less than that in the non-NP group (p = 0.039). In the multivariate analysis, systolic BP during sleep was significantly associated with NP (OR 0.970, p = 0.028). CONCLUSION: NP is associated with inadequate nocturnal blood pressure reduction in males, suggesting that reduction in nocturnal blood pressure may lead to improvement in nocturia.
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Sintomas do Trato Urinário Inferior , Noctúria , Humanos , Masculino , Noctúria/epidemiologia , Noctúria/etiologia , Noctúria/diagnóstico , Poliúria/complicações , Estudos Prospectivos , Pressão Sanguínea , Qualidade de VidaRESUMO
Hydroxyhydroquinone (HHQ) is an oxidative component produced by roasting coffee beans and has been reported to generate relatively large amounts of reactive oxygen species (ROS). In this study, we used senescence-accelerated mouse prone 8 (SAMP8) mice to determine whether HHQ consumption increases oxidative-stress-induced injury, because in SAMP8 mice, the activity of 8-oxoguanine DNA glycosylase 1, which repairs oxidative modifications in DNA, is decreased. The results showed that two out of twelve (16.7%) HHQ-treated mice presented polyuria and glucosuria around 2 months after the start of treatment, indicating that HHQ may act as a mutagen against SAMP8 mice, which is sensitive to oxidative damage. No abnormalities were observed in the chlorogenic acid (coffee polyphenol, CPP)-treated group. The concentration of hydrogen peroxide in the serum of SAMP8 mice was significantly higher than that in SAMR1 (senescence-resistant) control mice, and the concentration was further increased in the HHQ-treated group. CPP, when coexisting with HHQ at the rate contained in roasted coffee, decreased the amount of hydrogen peroxide in the serum of SAMP8 mice. Although CPP can act both oxidatively and antioxidatively as a polyphenol, CPP acts more antioxidatively when coexisting with HHQ. Thus, the oxidative effect of HHQ was shown to be counteracted by CPP.
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Ácido Clorogênico , Hidroquinonas , Polifenóis , Animais , Camundongos , Ácido Clorogênico/farmacologia , Polifenóis/farmacologia , Mutagênicos/toxicidade , Peróxido de Hidrogênio , Estresse Oxidativo , DNARESUMO
Diabetes mellitus (DM) is an uncommon, poorly documented metabolic disorder of birds. Extrapolating knowledge from DM in mammals is challenging because of marked differences in avian physiology and metabolism. A literature review from December 1991 to January 2022 identified 14 publications covering 16 diabetic birds, 63% (10/16) of which belonged to the order Psittaciformes with Ara as the predominant genus. No sex predilection was noted, but males generally presented at a younger age. Commonly reported clinical signs included polyuria 94% (15/16), polydipsia 88% (14/16), weight loss 75% (12/16), lethargy 63% (10/16), and polyphagia 38% (6/16). Diagnosis of DM was based on the presence of clinical signs and persistent hyperglycemia 100% (16/16), often with glucosuria 93% (13/14), response to insulin therapy 80% (8/10), and pancreatic pathology 90% (9/10). Specific treatment for DM was initiated in 14 patients, but blood glucose regulation for 6 months or longer was only achieved in 6 birds. Five of the regulated birds were managed with injectable long-acting insulin and 1 with oral glipizide combined with dietary modifications. However, glipizide yielded poor results in other cases, likely attributable to a lack of functional beta cells. Three diabetic birds progressed to remission. Treatment proved unsuccessful for 7 patients with a mean survival time of 36 days from diagnosis. One patient was lost to follow-up, and 2 were euthanized immediately following diagnosis. Histological examination of the pancreas frequently (90%, 9/10) revealed abnormalities including atrophy, fibrosis, and vacuolization of the endocrine islets with or without lymphoplasmacytic pancreatitis. Comorbidities, including hemosiderosis and infection, were common. This review suggests that birds diagnosed with DM are primarily affected by a type I diabetes as observed in dogs and humans. In contrast to mammalian species, avian DM is often associated with underlying disease and a complete clinical workup is essential to diagnose and address secondary disease conditions prior to initiating long-term insulin therapy.
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Doenças das Aves , Aves , Diabetes Mellitus , Animais , Doenças das Aves/patologia , Diabetes Mellitus/veterináriaRESUMO
Nocturia (waking to void) is prevalent among older adults. Disruption of the well-described circadian rhythm in urine production with higher nighttime urine output is its most common cause. In young adults, their circadian rhythm is modulated by the 24-h secretory pattern of hormones that regulate salt and water excretion, including antidiuretic hormone (ADH), renin, angiotensin, aldosterone, and atrial natriuretic peptide (ANP). The pattern of hormone secretion is less clear in older adults. We investigated the effect of sleep on the 24-h secretion of these hormones in healthy older adults. Thirteen participants aged ≥65 yr old underwent two 24-h protocols at a clinical research center 6 wk apart. The first used a habitual wake-sleep protocol, and the second used a constant routine protocol that removed the influence of sleep, posture, and diet. To assess hormonal rhythms, plasma was collected at 8:00 am, 12:00 pm, 4:00 pm, and every 30 min from 7:00 pm to 7:00 am. A mixed-effects regression model was used to compare subject-specific and mean trajectories of hormone secretion under the two conditions. ADH, aldosterone, and ANP showed a diurnal rhythm that peaked during sleep in the wake-sleep protocol. These nighttime elevations were significantly attenuated within subjects during the constant routine. We conclude that sleep has a masking effect on circadian rhythm amplitude of ADH, aldosterone, and ANP: the amplitude of each is increased in the presence of sleep and reduced in the absence of sleep. Disrupted sleep could potentially alter nighttime urine output in healthy older adults via this mechanism.NEW & NOTEWORTHY Nocturia (waking to void) is the most common cause of sleep interruption among older adults, and increased nighttime urine production is its primary etiology. We showed that in healthy older adults sleep affects the 24-h secretory rhythm of hormones that regulate salt-water balance, which potentially alters nighttime urine output. Further studies are needed to elucidate the impact of chronic insomnia on the secretory rhythms of these hormones.
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Aldosterona , Noctúria , Adulto Jovem , Humanos , Idoso , Micção , Sono/fisiologia , Ritmo Circadiano , PoliúriaRESUMO
OBJECTIVE: Copeptin is secreted in isomolar amounts along with arginine vasopressin peptide (AVP) from the neurohypophysis. Its stability makes it a perfect candidate for the endocrine approach in the diagnosis of AVP deficiency (AVPD; cranial diabetes insipidus; CDI). However, pediatric reference values are lacking. DESIGN AND PATIENTS: This is a monocentric retrospective analysis of donated residual serum samples from 72 children and adolescents who underwent arginine or growth hormone-releasing hormone-arginine stimulation to test GH secretory capacity from 2018 to 2022. MEASUREMENTS: Copeptin was measured in baseline, 30-, and 60-min samples by BRAHMS Copeptin proAVP Kryptor immunofluorescence assay. RESULTS: Of the 72 patients, 4 suffered from complete AVPD (CDI). The baseline level of copeptin in the 68 non-AVPD (non-CDI) patients was highly variable (range: 1.3-44.4 pmol/L). The increase after arginine was moderate (30 min range: 1.6-40.4 pmol/L). The median baseline and peak copeptin levels were 5.6 and 8.0 pmol/L, respectively. The 2.5th percentile of the baseline and peak values of copeptin were 2.1 and 3.3 pmol/L, respectively. The increase and peak value of copeptin were inversely related to age (R = -.405; p = .011, and R = -.335; p = .0072, respectively) but not to gender, body mass index (standard deviation score) or GH secretion. In the four patients with AVPD (CDI), baseline or stimulated copeptin was below the 2.5th percentile of non-AVPD (non-CDI) patients. CONCLUSIONS: Stimulated copeptin is a promising parameter for the differential diagnosis of polyuria-polydipsia syndrome. However, the low copeptin increase after arginine and the high limit of quantification of the assay are problematic for use in paediatrics.
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Arginina , Diabetes Insípido Neurogênico , Humanos , Criança , Adolescente , Estudos Retrospectivos , GlicopeptídeosRESUMO
Arginine vasopressin deficiency (AVP-D) is one of the main entities of the polyuria-polydipsia syndrome. Its correct diagnosis and differentiation from the other two causes - AVP resistance and primary polydipsia - is crucial as this determines the further management of these patients.Over the last years, several new diagnostic tests using copeptin, the stable surrogate marker of AVP, have been introduced. Among them, hypertonic saline stimulated copeptin was confirmed to reliably and safely improve the diagnostic accuracy to diagnose AVP-D. Due to its simplicity, arginine stimulated copeptin was put forward as alternative test procedure. Glucagon-stimulated copeptin also showed promising results, while the oral growth hormone secretagogue Macimorelin failed to provide a sufficient stimulus. Interestingly, an approach using machine learning techniques also showed promising results concerning diagnostic accuracy.Once AVP-D is diagnosed, further workup is needed to evaluate its etiology. This will partly define the further treatment and management. In general, treatment of AVP-D focuses on desmopressin substitution, with oral formulations currently showing the best tolerance and safety profile. However, in addition to desmopressin substitution, recent data also showed that psychopathological factors play an important role in managing AVP-D patients.
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INTRODUCTION: Patients with lower urinary tract symptoms (LUTS) can be subcategorized into polyuria, normal or oliguria groups. Polyuria may be caused by pathologies including diabetes mellitus (DM), chronic kidney disease (CKD), diabetes insipidus (DI), or primary polydipsia (PPD). While fluid restriction is appropriate for some, doing so in all may result in serious complications. This study investigates the prevalence of these pathologies in LUTS patients with polyuria. MATERIALS AND METHODS: Two databases were retrospectively queried for men and women who filled out a lower urinary tract symptom score (LUTSS) questionnaire, 24-h bladder diary (24HBD) and were polyuric (>2.5 L/day). Patients were divided into four groups: poorly controlled DM, DI, an CKD grade 3 and PPD. One-way analysis of variance compared 24HBD and LUTSS questionnaires. Pearson correlation examined LUTSS and bother with 24-h voided volume (24 HVV), maximum voided volume (MVV) and total voids. RESULTS: Among 814 patients who completed a 24HBD, 176 had polyuria (22%). Of the patients with complete data, 7.8% had poorly-controlled DM, 3.1% had DI, 4.7% had CKD grade 3% and 84.4% had PPD. Amongst the four different sub-groups, significant differences were seen in 24 HVV (p < 0.001), nocturnal urine volume (NUV) (p < 0.001), MVV (p = 0.003), daytime voids (p = 0.05), nocturnal polyuria index (NPi) (p < 0.001) and nocturia index (Ni) (p = 0.002). Significance was also seen between LUTSS and bother subscore (r = 0.68, p < 0.001), LUTSS and total voids (r = 0.29, p = 0.001) and bother sub-score and total voids (r = 0.21, p = 0.019). CONCLUSIONS: 22% of patients with LUTS were found to have polyuria based on a 24HBD. Within this cohort, four sub-populations were identified as being demonstrating statistically significant differences in 24 HVV, NUV, MVV, daytime voids, NPi and Ni. Identifying the underlying etiology of polyuria should be carried out to safely treat patients with LUTS.
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Sintomas do Trato Urinário Inferior , Noctúria , Masculino , Humanos , Feminino , Poliúria/epidemiologia , Poliúria/etiologia , Estudos Retrospectivos , Prevalência , Noctúria/epidemiologia , Noctúria/etiologia , Noctúria/diagnóstico , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/complicaçõesRESUMO
INTRODUCTION: Nocturia arises from a fundamental mismatch between nocturnal urine production, storage capacity, and sleep architecture, which may be driven by abnormalities of the genitourinary tract, but also by sleep disorders, medical diseases, patient actions/lifestyle factors, or medications. This article introduces a novel system for organizing the complex differential diagnosis for nocturia, as proposed by an international collective of practicing urologists, physician specialists, and sleep experts: "Sleep CALM"-Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications. METHODS: Narrative review of current evidence regarding the relevance of each "Sleep CALM" factor to nocturia pathogenesis, evaluation, and management. RESULTS: Nocturia and sleep disorders are highly intertwined and often bidirectional, such that nocturnal awakenings for reasons other than a sensation of bladder fullness should not be used as grounds for exclusion from nocturia treatment, but rather leveraged to broaden therapeutic options for nocturia. Nocturia is an important potential harbinger of several serious medical conditions beyond the genitourinary tract. Urologists should have a low threshold for primary care and medical specialty referral for medical optimization, which carries the potential to significantly improve nocturnal voiding frequency in addition to overall health status. Adverse patient actions/lifestyle factors, lower urinary tract dysfunction, and medication use commonly coexist with disordered sleep and comorbid medical conditions, and may be the primary mediators of nocturia severity and treatment response, or further exacerbate nocturia severity and complicate treatment. CONCLUSION: "Sleep CALM" provides a memorable and clinically relevant means by which to structure the initial patient history, physical exam, and clinical testing in accordance with current best-practice guidelines for nocturia. Although not intended as an all-encompassing diagnostic tool, the "Sleep CALM" schema may also be useful in guiding individualized ancillary testing, identifying the need for specialty referral and multidisciplinary care, and uncovering first-line treatment targets.