-
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 -
Australian Journal of General Practice Jul 2018Patients may not raise nocturia as a concern as they mistakenly consider the symptom to be a normal part of ageing. Nocturia is associated with significant morbidity and...
BACKGROUND
Patients may not raise nocturia as a concern as they mistakenly consider the symptom to be a normal part of ageing. Nocturia is associated with significant morbidity and is likely to be a marker of poor health.
OBJECTIVE
This paper provides questions to guide diagnosis, evaluation and individualised treatment of nocturia.
DISCUSSION
Nocturia results from the interplay between nocturnal polyuria, reduced bladder storage and sleep disruption. Changes in the function of the urinary bladder, kidneys, brain and cardiovascular system, and hormone status underlie the development and progression of nocturia. Medications commonly prescribed to older people can affect development or resolution of nocturia. The bother caused to a patient by waking to void relates to disturbance of slow-wave sleep, the physical act of getting out of bed and resulting chronic fatigue. An assessment process that identifies relevant and co-existing causes of an individual's nocturia will facilitate a targeted approach to treatment.
Topics: Humans; Hypertension; Kidney; Medical History Taking; Nocturia; Polyuria; Sleep Disorders, Circadian Rhythm
PubMed: 30114863
DOI: 10.31128/AJGP-01-18-4448 -
International Journal of Molecular... Feb 2019The renin-angiotensin system (RAS) plays an important role in regulating body fluids and blood pressure. However, inappropriate activation of the RAS contributes to the... (Review)
Review
The renin-angiotensin system (RAS) plays an important role in regulating body fluids and blood pressure. However, inappropriate activation of the RAS contributes to the pathogenesis of cardiovascular and renal diseases. Recently, sodium glucose cotransporter 2 (SGLT2) inhibitors have been used as anti-diabetic agents. SGLT2 inhibitors induce glycosuria and improve hyperglycemia by inhibiting urinary reabsorption of glucose. However, in the early stages of treatment, these inhibitors frequently cause polyuria and natriuresis, which potentially activate the RAS. Nevertheless, the effects of SGLT2 inhibitors on RAS activity are not straightforward. Available data indicate that treatment with SGLT2 inhibitors transiently activates the systemic RAS in type 2 diabetic patients, but not the intrarenal RAS. In this review article, we summarize current evidence of the diuretic effects of SGLT2 inhibitors and their influence on RAS activity.
Topics: Blood Pressure; Diabetes Mellitus, Type 2; Diuretics; Gene Expression; Glucose; Glycosuria; Humans; Hyperglycemia; Hypertension; Hypoglycemic Agents; Natriuresis; Polyuria; Renin-Angiotensin System; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 30717173
DOI: 10.3390/ijms20030629 -
Irish Journal of Psychological Medicine Mar 2022Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies... (Observational Study)
Observational Study
OBJECTIVES
Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies for polyuria in community lithium-treated patients.
METHODS
This is a naturalistic, observational, prospective 12-month cohort study of lithium-treated patients with polyuria attending a community mental health service in Dublin, Ireland. When polyuria was detected, management changed in one of four ways: (a) no pharmacological change; (b) lithium dose decrease; (c) lithium substitution; or (d) addition of amiloride.
RESULTS
Thirty-four participants were diagnosed with polyuria and completed prospective data over 12 months. Mean 24-hour urine volume decreased from 4852 to 4344 ml (p = 0.038). Mean early morning urine osmolality decreased from 343 to 338 mOsm/kg (p = 0.823). Mean 24-hour urine volume decreased with each type of intervention but did not attain statistical significance for any individual intervention group. Mean early morning urine osmolality decreased in participants with no pharmacological change and increased in participants who received a change in medication but these changes did not attain statistical significance. Only participants who discontinued lithium demonstrated potentially clinically significant changes in urine volume (mean decrease 747 ml in 24 hours) and early morning urine osmolality (mean increase 31 mOsm/kg) although this was not definitively proven, possibly owing to power issues.
CONCLUSIONS
Managing polyuria by decreasing lithium dose does not appear to substantially improve objective measures of renal tubular dysfunction, whereas substituting lithium may do so. Studies with larger numbers and longer follow-up would clarify these relationships.
Topics: Cohort Studies; Female; Humans; Lithium; Lithium Compounds; Male; Polyuria; Prospective Studies
PubMed: 30968793
DOI: 10.1017/ipm.2019.9 -
Indian Pediatrics Jan 2019Hyponatremic-hypertensive syndrome (HHS) is characterized by combination of polyuria, polydipsia, hypertension, hyponatremia and hypokalemia in association with...
BACKGROUND
Hyponatremic-hypertensive syndrome (HHS) is characterized by combination of polyuria, polydipsia, hypertension, hyponatremia and hypokalemia in association with unilateral renal artery stenosis.
CASE CHARACTERISTICS
A 10-year- old girl presented with polyuria, polydipsia, hypertension, hyponatremia, hypokalemia and proteinuria. Ultrasonography with doppler study revealed bilateral normal renal arteries. Completed tomography of abdomen detected a left adnexal mass, which was later confirmed as ovarian paraganglioma on histopathology.
OUTCOME
After tumor excision, polyuria subsided and blood pressure normalized.
MESSAGE
Hyponatremic-Hypertensive Syndrome does not always result from unilateral renal artery stenosis. High index of clinical suspicion with appropriate imaging technique may clinch rare endocrine causes of hypertension, like paraganglioma.
Topics: Child; Female; Humans; Hypertension; Hyponatremia; Nocturnal Enuresis; Ovarian Neoplasms; Paraganglioma; Polyuria; Syndrome; Tomography, X-Ray Computed
PubMed: 30806368
DOI: No ID Found -
Pediatrics in Review Aug 2014On the basis of strong evidence, although primary monosymptomatic nocturnal enuresis (PMNE) is common and most children will outgrow the condition spontaneously, the... (Review)
Review
On the basis of strong evidence, although primary monosymptomatic nocturnal enuresis (PMNE) is common and most children will outgrow the condition spontaneously, the psychological effect to the child can be significant and represents the main reason for treatment of these children. On the basis of international consensus panels, treatment of PMNE should be targeted toward the specific type of bedwetting patterns the child has, using bladder diary, sleep history, and daytime elimination concerns as a guide (Table 3). On the basis of international consensus panels, it is important for the primary care physician to be able to differentiate children with PMNE from children with nonmonosymptomatic nocturnal enuresis (NMNE) and secondary nocturnal enuresis. On the basis of international consensus panels, children with NMNE should have their underlying voiding or stool problem addressed before initiation of therapy for the nocturnal enuresis. On the basis of strong evidence, both the bedwetting alarm and desmopressin are considered first-line therapy for children with PMNE.
Topics: Child; Humans; Medical History Taking; Nocturnal Enuresis; Polyuria; Sleep Arousal Disorders; Urinary Bladder
PubMed: 25086164
DOI: 10.1542/pir.35-8-327 -
Cureus May 2017A 23-year-old male trauma patient with a cervical spine fracture underwent an anterior and posterior discectomy and spinal fusion surgery. The patient presented to the...
A 23-year-old male trauma patient with a cervical spine fracture underwent an anterior and posterior discectomy and spinal fusion surgery. The patient presented to the operating room with a stabilizing halo fixation device in place, and a fiberoptic intubation was performed with dexmedetomidine for sedation. During the surgical procedure, general anesthesia was maintained with a propofol and remifentanil infusion as the patient was monitored using somatosensory and motor evoked potentials. The patient's urine output increased gradually during the nine-hour surgical procedure from 150 mL/hour to over 700 mL/hour in the eighth hour of the procedure, where it remained until the end of the procedure. Postoperatively, the patient's laboratory values and urine output returned to baseline levels the following day. A search of the literature revealed few case reports of polyuria under similar conditions. Dexmedetomidine, being an alpha-2 agonist that blocks arginine-vasopressin release, may be responsible for inducing the polyuria noted in this patient case.
PubMed: 28589067
DOI: 10.7759/cureus.1218 -
Best Practice & Research. Clinical... Sep 2020Most cases of acquired central diabetes insipidus are caused by destruction of the neurohypophysis by: 1) anatomic lesions that destroy the vasopressin neurons by... (Review)
Review
Most cases of acquired central diabetes insipidus are caused by destruction of the neurohypophysis by: 1) anatomic lesions that destroy the vasopressin neurons by pressure or infiltration, 2) damage to the vasopressin neurons by surgery or head trauma, and 3) autoimmune destruction of the vasopressin neurons. Because the vasopressin neurons are located in the hypothalamus, lesions confined to the sella turcica generally do not cause diabetes insipidus because the posterior pituitary is simply the site of the axon terminals that secrete vasopressin into the bloodstream. In addition, the capacity of the neurohypophysis to synthesize vasopressin is greatly in excess of the body's needs, and destruction of 80-90% of the hypothalamic vasopressin neurons is required to produce diabetes insipidus. As a result, even large lesions in the sellar and suprasellar area generally are not associated with impaired water homeostasis until they are surgically resected. Regardless of the etiology of central diabetes insipidus, deficient or absent vasopressin secretion causes impaired urine concentration with resultant polyuria. In most cases, secondary polydipsia is able to maintain water homeostasis at the expense of frequent thirst and drinking. However, destruction of the osmoreceptors in the anterior hypothalamus that regulate vasopressin neuronal activity causes a loss of thirst as well as vasopressin section, leading to severe chronic dehydration and hyperosmolality. Vasopressin deficiency also leads to down-regulation of the synthesis of aquaporin-2 water channels in the kidney collecting duct principal cells, causing a secondary nephrogenic diabetes insipidus. As a result, several days of vasopressin administration are required to achieve maximal urine concentration in patients with CDI. Consequently, the presentation of patients with central diabetes insipidus can vary greatly, depending on the size and location of the lesion, the magnitude of trauma to the neurohypophysis, the degree of destruction of the vasopressin neurons, and the presence of other hormonal deficits from damage to the anterior pituitary.
Topics: Aquaporin 2; Brain Injuries, Traumatic; Diabetes Insipidus, Nephrogenic; Diabetes Insipidus, Neurogenic; Homeostasis; Humans; Neurophysins; Pituitary Diseases; Pituitary Gland, Posterior; Polydipsia; Polyuria; Protein Precursors; Vasopressins; Water-Electrolyte Balance
PubMed: 32792133
DOI: 10.1016/j.beem.2020.101449 -
Pediatric Nephrology (Berlin, Germany) Jul 2021Up to 50% of children with posterior urethral valves (PUV) progress to kidney failure. This study aimed to evaluate polyuria and polydipsia and other established...
Evaluation of polyuria and polydipsia along with other established prognostic factors in posterior urethral valves for progression to kidney failure: experience from a developing country.
BACKGROUND
Up to 50% of children with posterior urethral valves (PUV) progress to kidney failure. This study aimed to evaluate polyuria and polydipsia and other established variables with later development of kidney failure in children with PUV.
METHODS
Retrospective analysis of 297 children with PUV who underwent ablation of valves between January 1992 and January 2015 at our tertiary care center. Patients were divided into two groups: those who developed kidney failure (group 1) and those who did not (group 2). Specific prognostic factors for progression to kidney failure were analyzed including age at presentation < 1 year, nadir serum creatinine > 1.0 mg/dl, bilateral grade 3 or higher VUR at diagnosis, recurrent febrile UTIs, severe bladder dysfunction, polyuria, and polydipsia.
RESULTS
Thirty-eight (12.8%) patients progressed to kidney failure. Twenty-four and 64 patients were polyuric in group 1 and group 2 respectively (p < 0.001, Z-4.4666). Twenty-two and 61 patients were polydipsic in both groups respectively (p < 0.001). On univariate analysis, predicting variables were as follows: age at presentation < 1 year (p < 0.001), nadir serum creatinine > 1 mg/dl (p < 0.001), B/L high-grade VUR (p < 0.001), severe bladder dysfunction (p < 0.001), recurrent febrile UTIs (p = 0.002), polyuria (p < 0.001), and polydipsia (p < 0.001). On multivariate Cox regression analysis, severe bladder dysfunction, recurrent febrile UTIs, polyuria, and polydipsia were identified as significant prognostic factors predictive of ultimate progression to kidney failure.
CONCLUSION
Polyuria and polydipsia along with recurrent febrile UTI and bladder dysfunction are major prognostic factors affecting long-term kidney outcome in cases of PUV. Graphical abstract.
Topics: Child; Creatinine; Developing Countries; Humans; Infant; Male; Polydipsia; Polyuria; Prognosis; Renal Insufficiency; Retrospective Studies; Urethra; Urinary Tract Infections
PubMed: 33462698
DOI: 10.1007/s00467-020-04837-4 -
European Urology Focus Jan 2022Nocturia is a prevalent condition and may result from nocturnal polyuria, whereby overnight urine production is excessive. Anecdotal cases of idiopathic nocturnal... (Review)
Review
Nocturia is a prevalent condition and may result from nocturnal polyuria, whereby overnight urine production is excessive. Anecdotal cases of idiopathic nocturnal polyuria in which cerebrospinal fluid (CSF) disorders were identified suggest a potential mechanism. The skull constrains three circulatory systems: the CSF, interstitial fluid, and vascular supply. For each, fluid dynamics (pressure, volume, and flow) are closely regulated and adapt to changes such as recumbency and circadian variation. Pathologies disrupting this regulation, and thus impairing intracranial fluid dynamics, will place the brain environment at risk. Hence, compensatory responses are needed to maintain safe limits and prevent neurological deficits. We hypothesise that a change in the fluid dynamics for the intracranial CSF, interstitial, or vascular circulation means that positional or circadian changes during sleep trigger compensatory hormonal responses to protect the brain, but these also cause nocturnal polyuria. Natriuretic hormones are candidate mediators for protection against excess intracranial pressure or volume. PATIENT SUMMARY: A need to pass urine during the night, which is called nocturia, may be because of excessive overnight urine production. We propose that changes in fluid dynamics in the brain caused by lying down or daily body rhythms may trigger the release of hormones that could be a factor in nighttime urine production. This hypothesis should be explored in further investigations.
Topics: Humans; Nervous System Diseases; Nocturia; Polyuria
PubMed: 35058168
DOI: 10.1016/j.euf.2022.01.004