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Journal of Endocrinological... Jan 2020Copeptin is secreted in equimolar amount to Arginine Vasopressin (AVP) but can easily be measured with a sandwich immunoassay. Both peptides, copeptin and AVP, show a... (Review)
Review
COPEPTIN
Copeptin is secreted in equimolar amount to Arginine Vasopressin (AVP) but can easily be measured with a sandwich immunoassay. Both peptides, copeptin and AVP, show a high correlation. Accordingly, copeptin mirrors the amount of AVP in the circulation and its measurement provides an attractive marker in the differential diagnosis of diabetes insipidus.
THE POLYURIA POLYDIPSIA SYNDROME
Diabetes insipidus-either central or nephrogenic-has to be differentiated from primary polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since many decades, the "gold standard" for differential diagnosis has been the classical water deprivation test, which has several limitations leading to an overall limited diagnostic accuracy. In addition, the test has a long duration of 17 hours and is cumbersome for patients. Clinical signs and symptoms as well as MRI characteristics overlap between patients with diabetes insipidus and primary polydipsia. Direct measurement of AVP upon osmotic stimulation was first shown to overcome these limitations, but failed to enter clinical practice mainly due to technical limitations of the AVP assay.
COPEPTIN AS DIAGNOSTIC TOOL IN THE POLYURIA POLYDIPSIA SYNDROME
We have recently shown that copeptin, without prior water deprivation, identifies patients with nephrogenic diabetes insipidus. On the other hand, for the more difficult differentiation between central diabetes insipidus and primary polydipsia, a copeptin level of 4.9 pmol/L stimulated with hypertonic saline infusion differentiates between these two entities with a high diagnostic accuracy, and is superior to the water deprivation test. It is important to note that close sodium monitoring during the hypertonic saline test is a prerequisite.
CONCLUSION
Therefore, we propose that copeptin upon hypertonic saline infusion should become the new standard test in the differential diagnosis of diabetes insipidus.
Topics: Biomarkers; Diagnosis, Differential; Glycopeptides; Humans; Polyuria
PubMed: 31368050
DOI: 10.1007/s40618-019-01087-6 -
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 -
The Veterinary Record Jul 2019
Topics: Animals; Diagnosis, Differential; Dog Diseases; Dogs; Polydipsia; Polyuria
PubMed: 31346113
DOI: 10.1136/vr.l4865 -
Transplantation Proceedings May 2023To investigate the quality of life (QOL) of patients with nocturia after kidney transplantation (KT) and the association between nocturnal polyuria and sleep quality.
BACKGROUND
To investigate the quality of life (QOL) of patients with nocturia after kidney transplantation (KT) and the association between nocturnal polyuria and sleep quality.
METHODS
In a cross-sectional study, a patient who consented was evaluated using the following items: international prostate symptom QOL score, nocturia-quality of life score, overactive bladder symptom score, Pittsburgh sleep quality index, bladder diary, uroflowmetry, and bioimpedance analysis. Clinical and laboratory data were obtained from medical charts.
RESULTS
Forty-three patients were included in the analysis. Approximately 25% of patients urinated once at night, and 58.1% had nocturia twice. Nocturnal polyuria was observed in 86.0% of patients, and overactive bladder was observed in 23.3% of patients. According to the Pittsburgh sleep quality Index, 34.9% of patients had poor sleep quality. Multivariate analysis revealed that patients with nocturnal polyuria tended to have a high estimated glomerular filtration rate (P = .058). On the other hand, multivariate analysis for poor sleep quality revealed that high body fat percentage and low nocturia-quality of life total score were independently correlated factors (P = .008 and P = .012, respectively). Furthermore, the patients with nocturia ≥3/night were significantly older than those with nocturia ≤2/night (P = .022).
CONCLUSION
Nocturnal polyuria, poor sleep quality, and aging may decrease the QOL of patients with nocturia after KT. Further investigations, including optimal water intake and interventions, can lead to better management after KT.
Topics: Male; Humans; Nocturia; Urinary Bladder, Overactive; Polyuria; Quality of Life; Sleep Quality; Cross-Sectional Studies; Kidney Transplantation
PubMed: 36934056
DOI: 10.1016/j.transproceed.2023.02.045 -
Journal of Critical Care Jun 2023To identify cases of diabetes insipidus (DI) related to sedation in the ICU to determine which medications pose the greatest risk and understand patterns of presentation. (Review)
Review
PURPOSE
To identify cases of diabetes insipidus (DI) related to sedation in the ICU to determine which medications pose the greatest risk and understand patterns of presentation.
MATERIALS AND METHODS
We searched PubMed, Embase, Scopus, Google Scholar, and Web of Science. Search terms included "polyuria," "diabetes insipidus," "hypnotics and sedatives," "sedation," as well as individual medications. Case reports or series involving DI or polyuria related to sedation in the ICU were identified.
RESULTS
We identified 21 cases of diabetes insipidus or polyuria in the ICU attributed to a sedative. Dexmedetomidine was implicated in 42.9% of cases, followed by sevoflurane (33.3%) and ketamine (23.8%). Sevoflurane was implicated in all 7 cases in which it was used (100%; 95% CI 59.0%, 100.0%), dexmedetomidine in 9 of 11 cases (81.8%; 95% CI 48.2, 97.7), and ketamine in 5 of 9 cases (55.6%; 95% CI 21.2%, 86.3%).
CONCLUSIONS
Awareness of the potential for sedatives to cause DI may lead to greater identification with swifter medication discontinuation and subsequent resolution of DI.
Topics: Humans; Dexmedetomidine; Sevoflurane; Ketamine; Polyuria; Hypnotics and Sedatives; Intensive Care Units; Diabetes Insipidus; Diabetes Mellitus
PubMed: 36738631
DOI: 10.1016/j.jcrc.2022.154233 -
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 -
Journal of Veterinary Internal Medicine Sep 2021Glucocorticoids are used for a variety of purposes in veterinary medicine but often are associated with clinically important adverse effects. Polyuria and polydipsia are...
BACKGROUND
Glucocorticoids are used for a variety of purposes in veterinary medicine but often are associated with clinically important adverse effects. Polyuria and polydipsia are the most frustrating adverse effects noted by owners.
OBJECTIVE
To determine whether administration of desmopressin ameliorates polyuria and polydipsia associated with prednisolone administration.
ANIMALS
Seven healthy adult Walker Hounds.
METHODS
Prospective hypothesis testing study. Daily water intake and urine specific gravity (USG) were measured in dogs under 4 separate sequential conditions: no medications (C), prednisolone only (P), prednisolone and desmopressin (PD), and prednisolone after discontinuation of desmopressin (PAD).
RESULTS
When compared to baseline, 6 of 7 dogs became polydipsic after administration of prednisolone (0.5 mg/kg PO q12h). When desmopressin (5 μg/dog SC q12h) was administered to dogs receiving prednisolone, significant decreases in water intake and serum sodium concentration occurred, and USG increased significantly.
CONCLUSIONS AND CLINICAL IMPORTANCE
Administration of desmopressin to dogs receiving prednisolone significantly decreased water intake and serum sodium concentration, and increased USG. Our results suggest that, in some dogs, desmopressin ameliorates the most important adverse effect of prednisolone noted by owners, but that hyponatremia is an important complication associated with desmopressin use.
Topics: Animals; Deamino Arginine Vasopressin; Dog Diseases; Dogs; Glucocorticoids; Polyuria; Prednisolone; Prospective Studies
PubMed: 34448503
DOI: 10.1111/jvim.16250 -
Neurourology and Urodynamics Jan 2024Evidence 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... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Female; Humans; Male; Nocturia; Deamino Arginine Vasopressin; Polyuria; Antidiuretic Agents; Treatment Outcome; Multiple Sclerosis
PubMed: 37746880
DOI: 10.1002/nau.25291 -
BMC Neurology Oct 2015Natriuresis with polyuria is common after aneurysmal subarachnoid hemorrhage (aSAH). Previous studies have shown an increased risk of symptomatic cerebral vasospasm or...
BACKGROUND
Natriuresis with polyuria is common after aneurysmal subarachnoid hemorrhage (aSAH). Previous studies have shown an increased risk of symptomatic cerebral vasospasm or delayed cerebral ischemia (DCI) in patients with hyponatremia and/or the cerebral salt wasting syndrome (CSW). However, natriuresis may occur in the absence of hyponatremia or hypovolemia and it is not known whether the increase in DCI in patients with CSW is secondary to a concomitant hypovolemia or because the physiology that predisposes to natriuretic peptide release also predisposes to cerebral vasospasm. Therefore, we investigated whether polyuria per se was associated with vasospasm and whether a temporal relationship existed.
METHODS
A retrospective review of patients with aSAH was performed. Exclusion criteria were admission more than 48 h after aneurysmal rupture, death within 5 days, and the development of diabetes insipidus or acute renal failure. Polyuria was defined as > 6 liters of urine in a 24 h period. Vasospasm was defined as a mean velocity > 120 m/s on Transcranial Doppler Ultrasonography (TCDs) or by evidence of vasospasm on computerized tomography (CT) or catheter angiography. Multivariable logistic regression was performed to assess the relationship between polyuria and vasospasm.
RESULTS
95 patients were included in the study. 51 had cerebral vasospasm and 63 met the definition of polyuria. Patients with polyuria were significantly more likely to have vasospasm (OR 4.301, 95% CI 1.378-13.419) in multivariate analysis. Polyuria was more common in younger patients (52 vs 68, p <.001) but did not impact mortality after controlling for age and disease severity. The timing of the development of polyuria was clustered around the diagnosis of vasospasm and patients with polyuria developed vasospasm faster than those without polyuria.
CONCLUSIONS
Polyuria is common after aSAH and is significantly associated with cerebral vasospasm. The development of polyuria may be temporally related to the development of vasospasm. An increase in urine volume may be a useful clinical predictor of patients at risk for vasospasm.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Natriuresis; Polyuria; Retrospective Studies; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 26462796
DOI: 10.1186/s12883-015-0446-6