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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 Journal of Urology Mar 2013Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats. (Comparative Study)
Comparative Study
PURPOSE
Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats.
MATERIALS AND METHODS
A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder.
RESULTS
Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes.
CONCLUSIONS
Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may have a pathogenic role in late stage diabetic bladder dysfunction.
Topics: Animals; Diabetes Mellitus, Experimental; Female; Hyperglycemia; Oxidative Stress; Polyuria; Rats; Rats, Sprague-Dawley; Urinary Bladder Diseases; Urination
PubMed: 22999997
DOI: 10.1016/j.juro.2012.08.222 -
The Yale Journal of Biology and Medicine 1984This article will provide a pathophysiologic basis for the assessment of critically ill children who have developed disorders of urine volume. The anatomical and... (Review)
Review
This article will provide a pathophysiologic basis for the assessment of critically ill children who have developed disorders of urine volume. The anatomical and pathophysiologic causes of oliguria and polyuria are considered. The physiologic basis for the use of urinary sodium and osmolarity as a guide to the assessment of patients with disorders of urine volume are discussed in detail. In addition, guidelines for the management of children with acute renal failure, with particular emphasis on the consideration for nutritional support of these patients, is discussed as a part of the comprehensive approach to this problem. This article emphasizes an understanding of the pathophysiology of salt and water excretion by the kidney as a foundation to the diagnosis and management of patients with oliguria and polyuria.
Topics: Acute Kidney Injury; Anuria; Child; Child, Preschool; Critical Care; Humans; Hypertension; Infant; Infant, Newborn; Kidney; Nutritional Physiological Phenomena; Oliguria; Polyuria; Vasopressins; Water-Electrolyte Imbalance
PubMed: 6375163
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... Feb 2019Er Shen Wan (ESW), has been empirically used for treating spleen-kidney Yang deficiency (SKYD) syndrome in Traditional Chinese medicine (TCM) for centuries and shows a...
ETHNOPHARMACOLOGICAL RELEVANCE
Er Shen Wan (ESW), has been empirically used for treating spleen-kidney Yang deficiency (SKYD) syndrome in Traditional Chinese medicine (TCM) for centuries and shows a variety of activities. The medicinal formula is a mixture of two component herbs, Psoraleae Fructus (PF, Bu-Gu-Zhi in Chinese) and Myristicae Semen (MS, Rou-Dou-Kou in Chinese). The current study was designed to evaluate ESWP antidiuretic treatment of polyuria and to explore potential mechanisms of renal water metabolism in the rat model of SKYD-induced diarrhea.
MATERIALS AND METHODS
An animal model of 'SKYD-induced diarrhea syndrome' has been established to evaluate the therapeutic effect and action mechanism according to the clinical syndrome and symptoms. The optimal dose (3.5 g/kg) of ESWP was given to rats by gavage for two weeks. Urinary volumes after 24 h were recorded. After the end of the trial, macroscopic morphological and histological examination of the kidney were conducted. Serum levels of Arginine vasopressin (AVP) and aldosterone (ALD) were also measured. Additionally, quantitative real-time RT-PCR (RT-qPCR) and immunohistochemistry (IHC) analyses were performed to clarify the regulation of aquaporin 2 (AQP 2) and arginine vasopressin type 2 receptor (AVPR 2) in the kidney at the gene and tissue expression levels respectively.
RESULTS
After the administration of ESWP, urinary output volume after 24 h was found to be significantly decreased in rats. Elevated plasma levels of AVP and ALD were detected. Histological kidney damage appeared to be impeded, and histological disease scores were reduced. In addition, the expression levels of AQP 2 and AVPR 2 were significantly increased.
CONCLUSION
This study suggests that ESWP may elicit significant effects on the treatment of polyuria. Potential mechanisms at least partially involve hormone regulation, and alleviating renal pathological damage. Simultaneously, ESWP may alter renal water absorption by increasing AQP 2 and AVPR 2 expression levels. Thus, the in vivo experimental evidence indicates that ESWP has a therapeutic effect on the SKYD syndrome, which is consistent with its traditional usage.
Topics: Animals; Aquaporin 2; Diarrhea; Disease Models, Animal; Drugs, Chinese Herbal; Kidney; Male; Polyuria; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Spleen; Yang Deficiency
PubMed: 30522016
DOI: 10.1016/j.biopha.2018.11.147 -
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 -
Frontiers in Endocrinology 2023The coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease....
INTRODUCTION
The coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential.
CASE PRESENTATION
A 16-year-old boy presented to the Paediatric Emergency Department with polyuria, polydipsia and weight loss over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after first dose of anti-COVID-19 BNT162b2 Comirnaty vaccine and then worsened after the second dose. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits. Daily fluid balance monitoring confirmed polyuria and polydipsia. Biochemistry laboratory analysis and urine culture were normal. Serum osmolality was 297 mOsm/Kg HO (285-305), whereas urine osmolality was 80 mOsm/Kg HO (100-1100), suggesting diabetes insipidus. Anterior pituitary function was preserved. Since parents refused to give consent to water deprivation test, treatment with Desmopressin was administered and confirmed ex juvantibus diagnosis of AVP deficiency (or central diabetes insipidus). Brain MRI revealed pituitary stalk thickening (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient's symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and still undetectable posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing.
CONCLUSION
Hypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID-19 vaccine and AVP deficiency.
Topics: Adolescent; Humans; Male; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Hypophysitis; Hypopituitarism; Immunization; Polydipsia; Polyuria; SARS-CoV-2
PubMed: 37143723
DOI: 10.3389/fendo.2023.1166953 -
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 -
Internal Medicine (Tokyo, Japan) Oct 2004
Topics: Brain Diseases; Diabetes Mellitus; Diagnosis, Differential; Humans; Hypothalamus; Pituitary Diseases; Pituitary Gland; Polyuria; Sarcoidosis
PubMed: 15575234
DOI: 10.2169/internalmedicine.43.894 -
PloS One 2022Hyperglycemia-induced transcriptional alterations lead to aberrant synthesis of a large number of pathogenetic molecules leading to functional and structural damage to...
BACKGROUND
Hyperglycemia-induced transcriptional alterations lead to aberrant synthesis of a large number of pathogenetic molecules leading to functional and structural damage to multiple end organs including the kidneys. Diabetic nephropathy (DN) remains a major cause of end stage renal disease. Multiple epigenetic mechanisms, including alteration of long non-coding RNAs (lncRNAs) may play a significant role mediating the cellular transcriptional activities. We have previously shown that lncRNA ANRIL may mediate diabetes associated molecular, functional and structural abnormalities in DN. Here we explored downstream mechanisms of ANRIL alteration in DN.
METHODS
We used renal cortical tissues from ANRIL knockout (KO) mice and wild type (WT) mice, with or without streptozotocin (STZ) induced diabetes for RNA sequencing. The differentially expressed genes were identified using edgeR and DESeq2 computational methods. KEGG and Reactome pathway analyses and network analyses using STRING and IPA were subsequently performed.
RESULTS
Diabetic animals showed hyperglycemia, reduced body weight gain, polyuria and increased urinary albumin. Both albuminuria and polyuria were corrected in the KO diabetic mice. RNA analyses showed Diabetes induced alterations of a large number of transcripts in the wild type (WT) animals. ANRIL knockout (KO) prevented a large number of such alterations. The altered transcripts include metabolic pathways, apoptosis, extracellular matrix protein synthesis and degradation, NFKB related pathways, AGE-RAGE interaction pathways etc. ANRIL KO prevented majority of these pathways.
CONCLUSION
These findings suggest that as ANRIL regulates a large number of molecules of pathogenetic significance, it may potentially be a drug target for DN and other chronic diabetic complications.
Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Hyperglycemia; Mice; Mice, Knockout; Polyuria; RNA, Long Noncoding
PubMed: 35984863
DOI: 10.1371/journal.pone.0270287 -
Therapeutic Advances in Urology Dec 2013Nocturia is a common and bothersome condition experienced by both men and women. Studies have suggested that nocturia contributes a level of morbidity to those who... (Review)
Review
Nocturia is a common and bothersome condition experienced by both men and women. Studies have suggested that nocturia contributes a level of morbidity to those who suffer from the condition, both young and old. Desmopressin has historically been utilized to treat conditions such as central diabetes insipidus, certain bleeding disorders and primary nocturnal enuresis. Recently, interest has increased as to the use of desmopressin (a vasopressin analog) in the treatment of adult nocturia, for whom nocturnal polyuria is prevalent. While desmopressin has been traditionally administered in tablet and bioequivalent high dose melt formulations, newer low-dose orally disintegrating sublingual desmopressin has been recently studied to determine safe and efficacious dosing strategies. In this review, nocturia and its associated morbidities are discussed, followed by a contemporary literature review regarding the safety and efficacy of desmopressin for its treatment.
PubMed: 24294289
DOI: 10.1177/1756287213502116