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Swiss Medical Weekly 2012Recent discoveries have shed new light on the understanding of water metabolism: (1.) in addition to hypothalamic osmoreceptor cells expressing a TRPV1 variant, there... (Review)
Review
Recent discoveries have shed new light on the understanding of water metabolism: (1.) in addition to hypothalamic osmoreceptor cells expressing a TRPV1 variant, there are peripheral TRPV4 receptors sensing tonicity in the portal vein and changing central vasopressin secretion and peripheral autonomic activity; (2.) the central osmoregulatory gain of angiotensin action participates in the non-osmotic release of vasopressin induced by hypovolaemia; (3.) prostaglandins EP2 receptors on principal cells of the collecting ducts positively regulate urine concentration mechanisms. These new developments are important clinically for the understanding of hereditary polyuric states. We recommend sequencing of the nephrogenic diabetes insipidus genes in all affected patients. This genomic information is key to the routine care of patients with congenital polyuria and, as in other genetic diseases, reduces health costs and confers psychological benefits on patients and families.
Topics: Arginine Vasopressin; Diabetes Insipidus; Humans; Kidney; Neurons, Afferent; Osmolar Concentration; Polyuria; Sodium; TRPV Cation Channels; Water-Electrolyte Balance
PubMed: 22802123
DOI: 10.4414/smw.2012.13613 -
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 -
Reviews in Urology 2018Nocturia is a condition that has a tremendous impact on a patient's health and wellbeing. Getting up 2 or more times a night to urinate fragments sleep, preventing deep,...
Nocturia is a condition that has a tremendous impact on a patient's health and wellbeing. Getting up 2 or more times a night to urinate fragments sleep, preventing deep, restorative stages of the sleep cycle. With safer and more effective therapies, nocturia is a treatable condition that no longer should be overlooked. The simplicity of directly targeting the cause of nocturia, the overproduction of urine (ie, nocturnal polyuria) should be considered. Noctiva™ (desmopressin acetate) nasal spray (Avadel Pharmaceuticals plc, Chesterfield, MO), a novel FDA-approved microdose desmopressin nasal spray, can reduce nighttime urine production and potentially mitigate the potential harm of nocturia.
PubMed: 30787675
DOI: 10.3909/riu0822 -
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 -
Case Reports in Pediatrics 2018Psychogenic polydipsia is a well-described phenomenon in those with a diagnosed psychiatric disorder such as schizophrenia and anxiety disorders. Primary polydipsia is...
Psychogenic polydipsia is a well-described phenomenon in those with a diagnosed psychiatric disorder such as schizophrenia and anxiety disorders. Primary polydipsia is differentiated from psychogenic polydipsia by the lack of a clear psychotic disturbance. We present a case of a 27-month-old boy who presented with polyuria and polydipsia. Laboratory studies, imaging, and an observed water deprivation test were consistent with primary polydipsia. Polydipsia resolved after family limited his fluid intake and began replacing water drinking with other transition objects and behaviors for self-soothing. This case highlights the importance of water deprivation testing to differentiate between causes of polyuria, thereby avoiding misdiagnosis and iatrogenic hyponatremia. Secondly, primary polydipsia can result during the normal stages of child development without overt psychiatric disturbances.
PubMed: 30210889
DOI: 10.1155/2018/4281217 -
Revista Medica de Chile May 2013In patients with acute cerebral injury, polyuric states can potentially trigger, maintain and aggravate the primary neurological damage, due to hypovolemia, arterial... (Review)
Review
In patients with acute cerebral injury, polyuric states can potentially trigger, maintain and aggravate the primary neurological damage, due to hypovolemia, arterial hypotension and alterations of osmolarity. The true incidence of the condition in this population is unknown. A widely validated definition of polyuric state is lacking and its etiology is multifactorial. There are two principal classes of polyuria: (a) aqueous polyuria with diabetes insipidus as the main cause; and (b) osmotic polyuria in which sodium, glucose or ureaplay the main role. Polyuric states are in close association with disorders of water and sodium metabolism and with alterations in acid-base balance. A detailed analysis of the history, clinical picture and simple laboratory determinations in blood and urine, are required for an adequate assessment of these polyuric states. The problem must be faced with pathophysiological reasoning and a systematic and sequential approach, because each disorder needs a specific therapy.
Topics: Brain Injuries; Humans; Polyuria
PubMed: 24089277
DOI: 10.4067/S0034-98872013000500010 -
The Journal of Physiology Apr 2017Hypercalcaemia can occur under various pathological conditions, such as primary hyperparathyroidism, malignancy or granulomatosis, and it induces natriuresis and...
KEY POINTS
Hypercalcaemia can occur under various pathological conditions, such as primary hyperparathyroidism, malignancy or granulomatosis, and it induces natriuresis and polyuria in various species via an unknown mechanism. A previous study demonstrated that hypercalcaemia induced by vitamin D in rats increased endothelin (ET)-1 expression in the distal nephron, which suggests the involvement of the ET system in hypercalcaemia-induced effects. In the present study, we demonstrate that, during vitamin D-induced hypercalcaemia, the activation of ET system by increased ET-1 is responsible for natriuresis but not for polyuria. Vitamin D-treated hypercalcaemic mice showed a blunted response to amiloride, suggesting that epithelial sodium channel function is inhibited. We have identified an original pathway that specifically mediates the effects of vitamin D-induced hypercalcaemia on sodium handling in the distal nephron without affecting water handling.
ABSTRACT
Acute hypercalcaemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. Because vitamin D-induced hypercalcaemia increases the renal expression of endothelin (ET)-1, we hypothesized that ET-1 mediates the effects of hypercalcaemia on renal sodium and water handling. Hypercalcaemia was induced in 8-week-old, parathyroid hormone-supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT-treated mice became hypercalcaemic and displayed increased urinary water and sodium excretion compared to controls. mRNA levels of ET-1 and the transcription factors CCAAT-enhancer binding protein β and δ were specifically increased in the distal convoluted tubule and downstream segments in DHT-treated mice. To examine the role of the ET system in hypercalcaemia-induced natriuresis and polyuria, mice were treated with the ET-1 receptor antagonist macitentan, with or without DHT. Mice treated with both macitentan and DHT displayed hypercalcaemia and polyuria similar to that in mice treated with DHT alone; however, no increase in urinary sodium excretion was observed. To identify the affected sodium transport mechanism, we assessed the response to various diuretics in control and DHT-treated hypercalcaemic mice. Amiloride, an inhibitor of the epithelial sodium channel (ENaC), increased sodium excretion to a lesser extent in DHT-treated mice compared to control mice. Mice treated with either macitentan+DHT or macitentan alone had a similar response to amiloride. In summary, vitamin D-induced hypercalcaemia increases the renal production of ET-1 and decreases ENaC activity, which is probably responsible for the rise in urinary sodium excretion but not for polyuria.
Topics: Acute Disease; Animals; Cell Line, Transformed; Endothelin-1; Hypercalcemia; Kidney Tubules; Male; Mice; Mice, Inbred C57BL; Natriuresis; Polyuria; Vitamin D
PubMed: 28120456
DOI: 10.1113/JP273610 -
FASEB Journal : Official Publication of... Feb 2019cAMP is a universal second messenger regulating a plethora of processes in the kidney. Two downstream effectors of cAMP are PKA and exchange protein directly activated...
cAMP is a universal second messenger regulating a plethora of processes in the kidney. Two downstream effectors of cAMP are PKA and exchange protein directly activated by cAMP (Epac), which, unlike PKA, is often linked to elevation of [Ca]. While both Epac isoforms (Epac1 and Epac2) are expressed along the nephron, their relevance in the kidney remains obscure. We combined ratiometric calcium imaging with quantitative immunoblotting, immunofluorescent confocal microscopy, and balance studies in mice lacking Epac1 or Epac2 to determine the role of Epac in renal water-solute handling. Epac1 and Epac2 mice developed polyuria despite elevated arginine vasopressin levels. We did not detect major deficiencies in arginine vasopressin [Ca] signaling in split-opened collecting ducts or decreases in aquaporin water channel type 2 levels. Instead, sodium-hydrogen exchanger type 3 levels in the proximal tubule were dramatically reduced in Epac1 and Epac2 mice. Water deprivation revealed persisting polyuria, impaired urinary concentration ability, and augmented urinary excretion of Na and urea in both mutant mice. In summary, we report a nonredundant contribution of Epac isoforms to renal function. Deletion of Epac1 and Epac2 decreases sodium-hydrogen exchanger type 3 expression in the proximal tubule, leading to polyuria and osmotic diuresis.-Cherezova, A., Tomilin, V., Buncha, V., Zaika, O., Ortiz, P. A., Mei, F., Cheng, X., Mamenko, M., Pochynyuk, O. Urinary concentrating defect in mice lacking Epac1 or Epac2.
Topics: Animals; Aquaporin 2; Arginine Vasopressin; Calcium Signaling; Diuresis; Gene Deletion; Guanine Nucleotide Exchange Factors; Kidney; Kidney Concentrating Ability; Mice; Mice, Knockout; Osmosis; Polyuria; Sodium-Hydrogen Exchanger 3
PubMed: 30252533
DOI: 10.1096/fj.201800435R -
Revista Medica de Chile Apr 2023The relief of the impediment to urinary flow is the treatment of acute kidney failure due to urinary tract obstruction. However, there is a risk of inducing massive...
The relief of the impediment to urinary flow is the treatment of acute kidney failure due to urinary tract obstruction. However, there is a risk of inducing massive polyuria, which can be self-limited or produce severe contraction of the intravascular volume with pre-renal acute kidney failure and alterations in the internal environment. Polyuria, urine output > 3 L/d or > 200 mL/min for more than 2 hours, can have multiple causes, and can be classified as osmotic, aqueous or mixed. Post-obstructive polyuria obeys different pathogenic mechanisms, which overlap and vary during a patient's evolution. Initially, there is a decrease in vasoconstrictor factors and an increase in renal blood flow, which, added to the excess of urea accumulated, will cause intense osmotic diuresis (osmotic polyuria due to urea). Added to these factors are the positive sodium and water balance during acute renal failure, plus the contributions of crystalloid solutions to replace diuresis (ionic osmotic polyuria). Finally, there may be tubular dysfunction and decreased solutes in the renal medullary interstitium, adding resistance to the action of vasopressin. The latter causes a loss of free water (mixed polyuria). We present the case of a patient with post-obstructive polyuria where, by analyzing the clinical symptoms and laboratory alterations, it was possible to interpret the mechanisms of polyuria and administer appropriate treatment for the pathogenic mechanism.
Topics: Humans; Male; Polyuria; Ureteral Obstruction; Urethral Obstruction; Middle Aged
PubMed: 38687528
DOI: 10.4067/s0034-98872023000400518 -
BMC Medicine Jun 2023There are few large-scale studies evaluating the safety of the sodium-glucose cotransporter-2 inhibitor, dapagliflozin, in Chinese patients with type 2 diabetes. DONATE,...
A multicentre, prospective, non-interventional study evaluating the safety of dapagliflozin in patients with type 2 diabetes in routine clinical practice in China (DONATE).
BACKGROUND
There are few large-scale studies evaluating the safety of the sodium-glucose cotransporter-2 inhibitor, dapagliflozin, in Chinese patients with type 2 diabetes. DONATE, a multicentre, single-arm, prospective, non-interventional study, is the first real-world study evaluating the safety of dapagliflozin in Chinese patients with type 2 diabetes in routine clinical practice.
METHODS
Between August 2017 and July 2020, patients with type 2 diabetes who had initiated dapagliflozin therapy and received ≥1 dose were prospectively recruited from 88 hospitals in China. Patients were subsequently followed up for 24 weeks; if patients discontinued dapagliflozin they were followed up for an additional 7 days after treatment discontinuation. The primary outcome was the proportion of patients with adverse events and serious adverse events, particularly key adverse events of special interest (AESI) including urinary tract infection, genital tract infection (typical symptoms with or without microbiological diagnosis) and hypoglycaemia (typical symptoms with or without blood glucose ≤3.9 mmol/L, or blood glucose ≤3.9 mmol/L without symptoms). Exploratory outcomes included the absolute change in metabolic parameters and the proportion of patients with other AESI including volume depletion, abnormal blood electrolytes, polyuria, renal impairment, diabetic ketoacidosis, hepatic impairment and haematuria.
RESULTS
A total of 3000 patients were enrolled, of whom 2990 (99.7%) were included in the safety analysis set. Mean (SD) age was 52.6 (12.0) years, and 65.8% of patients were male. Mean (SD) duration of type 2 diabetes at enrolment was 8.4 (7.1) years. Mean (SD) treatment duration of dapagliflozin was 209.1 (157.6) days. Adverse events were reported in 35.4% (n = 1059) of patients during the 24-week follow-up period. Overall, 9.0% (n = 268) were related to treatment and 6.2% (n = 186) were serious. Urinary tract infection, genital tract infection and hypoglycaemia were reported in 2.3% (n = 70), 1.3% (n = 39) and 1.1% (n = 32) of patients, respectively. The proportion of patients with other AESI was also low: polyuria (0.7%; n = 21), volume depletion (0.3%; n = 9), renal impairment (0.3%; n = 8), hepatic impairment (0.2%; n = 7), haematuria (0.2%; n = 6) and diabetic ketoacidosis (0.1%; n = 2).
CONCLUSIONS
This study demonstrated that once-daily dapagliflozin was well tolerated in Chinese patients with type 2 diabetes and the overall safety profile of dapagliflozin in clinical practice in China was consistent with that reported in clinical trials.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03156985. Registered on 16 May, 2017.
Topics: Humans; Male; Middle Aged; Female; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Blood Glucose; Hematuria; Polyuria; Prospective Studies; Reproductive Tract Infections; Sodium-Glucose Transporter 2 Inhibitors; China; Hypoglycemia
PubMed: 37316847
DOI: 10.1186/s12916-023-02906-7