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Journal of Pediatric Endocrinology &... Apr 2022Nephrogenic diabetes insipidus (NDI) is characterized by the inability to concentrate urine that results in polyuria and polydipsia, despite having normal or elevated... (Review)
Review
Nephrogenic diabetes insipidus (NDI) is characterized by the inability to concentrate urine that results in polyuria and polydipsia, despite having normal or elevated plasma concentrations of arginine vasopressin (AVP). In this study, we review the clinical aspects and diagnosis of NDI, the various etiologies, current treatment options and potential future developments. NDI has different clinical manifestations and approaches according to the etiology. Hereditary forms of NDI are mainly caused by mutations in the genes that encode key proteins in the AVP signaling pathway, while acquired causes are normally associated with specific drug exposure, especially lithium, and hydroelectrolytic disorders. Clinical manifestations of the disease vary according to the degree of dehydration and hyperosmolality, being worse when renal water losses cannot be properly compensated by fluid intake. Regarding the diagnosis of NDI, it is important to consider the symptoms of the patient and the diagnostic tests, including the water deprivation test and the baseline plasma copeptin measurement, a stable surrogate biomarker of AVP release. Without proper treatment, patients may developcomplications leading to high morbidity and mortality, such as severe dehydration and hypernatremia. In that sense, the treatment of NDI consists in decreasing the urine output, while allowing appropriate fluid balance, normonatremia, and ensuring an acceptable quality of life. Therefore, therapeutic options include nonpharmacological interventions, including sufficient water intake and a low-sodium diet, and pharmacological treatment. The main medications used for NDI are thiazide diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and amiloride, used isolated or in combination.
Topics: Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Diabetes Mellitus; Humans; Mutation; Polyuria; Quality of Life
PubMed: 35146976
DOI: 10.1515/jpem-2021-0566 -
Nephrology, Dialysis, Transplantation :... Jan 2022
Topics: Amiloride; Calcium; Humans
PubMed: 34264323
DOI: 10.1093/ndt/gfab221 -
Pflugers Archiv : European Journal of... Jan 2021The variety of taste sensations, including sweet, umami, bitter, sour, and salty, arises from diverse taste cells, each of which expresses specific taste sensor... (Review)
Review
The variety of taste sensations, including sweet, umami, bitter, sour, and salty, arises from diverse taste cells, each of which expresses specific taste sensor molecules and associated components for downstream signal transduction cascades. Recent years have witnessed major advances in our understanding of the molecular mechanisms underlying transduction of basic tastes in taste buds, including the identification of the bona fide sour sensor H channel OTOP1, and elucidation of transduction of the amiloride-sensitive component of salty taste (the taste of sodium) and the TAS1R-independent component of sweet taste (the taste of sugar). Studies have also discovered an unconventional chemical synapse termed "channel synapse" which employs an action potential-activated CALHM1/3 ion channel instead of exocytosis of synaptic vesicles as the conduit for neurotransmitter release that links taste cells to afferent neurons. New images of the channel synapse and determinations of the structures of CALHM channels have provided structural and functional insights into this unique synapse. In this review, we discuss the current view of taste transduction and neurotransmission with emphasis on recent advances in the field.
Topics: Animals; Humans; Synapses; Synaptic Transmission; Taste; Taste Buds
PubMed: 32936320
DOI: 10.1007/s00424-020-02464-4 -
The Medical Letter on Drugs and... May 2020
Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension
PubMed: 32555118
DOI: No ID Found -
Journal of the... 2020Amiloride is a potassium retaining diuretic and natriuretic which acts by reversibly blocking luminal epithelial sodium channels (ENaCs) in the late distal tubule and... (Review)
Review
Amiloride is a potassium retaining diuretic and natriuretic which acts by reversibly blocking luminal epithelial sodium channels (ENaCs) in the late distal tubule and collecting duct. Amiloride is indicated in oedematous states, and for potassium conservation adjunctive to thiazide or loop diuretics for hypertension, congestive heart failure and hepatic cirrhosis with ascites. Historical studies on its use in hypertension were poorly controlled and there is insufficient data on dose-response. It is clearly highly effective in combination with thiazide diuretics where it counteracts the adverse metabolic effects of the thiazides and its use in the Medical Research Council Trial of Older Hypertensive Patients, demonstrated convincing outcome benefits on stroke and coronary events. Recently it has been shown to be as effective as spironolactone in resistant hypertension but there is a real need to establish its potential role in the much larger number of patients with mild to moderate hypertension in whom there is a paucity of information with amiloride particularly across an extended dose range.
Topics: Amiloride; Animals; Clinical Trials as Topic; Diuretics; Humans; Hypertension
PubMed: 33234024
DOI: 10.1177/1470320320975893 -
Vnitrni Lekarstvi 2022Liddle syndrome is an inherited form of arterial hypertension with autosomal dominant pattern of inheritance. It is caused by activating mutation of genes coding of the...
Liddle syndrome is an inherited form of arterial hypertension with autosomal dominant pattern of inheritance. It is caused by activating mutation of genes coding of the epithelial sodium channel in distal nephron. Mutation leads to excessive reabsorbtion of sodium ions and volume expansion resulting in arterial hypertension. Antoher typical laboratory findings are hypokalaemia, low levels of serum aldosteron and metabolic alkalosis. Phenotypic variability makes it difficult to identify patients with Liddle syndrome, often resulting in misdiagnosis and severe complications at early age. Genetic studies should be done to confirm the diagnosis. Therapy of Liddle syndrome is based on administration of epithelial sodium channel blocker amilorid.
Topics: Humans; Liddle Syndrome; Epithelial Sodium Channels; Hypertension; Hypokalemia; Mutation
PubMed: 36575060
DOI: 10.36290/vnl.2022.115 -
The Journal of Clinical Investigation Jan 2024Mineralocorticoid excess commonly leads to hypertension (HTN) and kidney disease. In our study, we used single-cell expression and chromatin accessibility tools to...
Mineralocorticoid excess commonly leads to hypertension (HTN) and kidney disease. In our study, we used single-cell expression and chromatin accessibility tools to characterize the mineralocorticoid target genes and cell types. We demonstrated that mineralocorticoid effects were established through open chromatin and target gene expression, primarily in principal and connecting tubule cells and, to a lesser extent, in segments of the distal convoluted tubule cells. We examined the kidney-protective effects of steroidal and nonsteroidal mineralocorticoid antagonists (MRAs), as well as of amiloride, an epithelial sodium channel inhibitor, in a rat model of deoxycorticosterone acetate, unilateral nephrectomy, and high-salt consumption-induced HTN and cardiorenal damage. All antihypertensive therapies protected against cardiorenal damage. However, finerenone was particularly effective in reducing albuminuria and improving gene expression changes in podocytes and proximal tubule cells, even with an equivalent reduction in blood pressure. We noted a strong correlation between the accumulation of injured/profibrotic tubule cells expressing secreted posphoprotein 1 (Spp1), Il34, and platelet-derived growth factor subunit b (Pdgfb) and the degree of fibrosis in rat kidneys. This gene signature also showed a potential for classifying human kidney samples. Our multiomics approach provides fresh insights into the possible mechanisms underlying HTN-associated kidney disease, the target cell types, the protective effects of steroidal and nonsteroidal MRAs, and amiloride.
Topics: Rats; Humans; Animals; Mineralocorticoid Receptor Antagonists; Chromatin; Amiloride; Mineralocorticoids; Kidney; Hypertension; Kidney Diseases; Gene Expression Profiling
PubMed: 37906287
DOI: 10.1172/JCI157165