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Endocrine Reviews Sep 2023Hyponatremia is the most common electrolyte disorder, affecting more than 15% of patients in the hospital. Syndrome of inappropriate antidiuresis (SIAD) is the most... (Review)
Review
Hyponatremia is the most common electrolyte disorder, affecting more than 15% of patients in the hospital. Syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hypotonic hyponatremia, mediated by nonosmotic release of arginine vasopressin (AVP, previously known as antidiuretic hormone), which acts on the renal V2 receptors to promote water retention. There are a variety of underlying causes of SIAD, including malignancy, pulmonary pathology, and central nervous system pathology. In clinical practice, the etiology of hyponatremia is frequently multifactorial and the management approach may need to evolve during treatment of a single episode. It is therefore important to regularly reassess clinical status and biochemistry, while remaining alert to potential underlying etiological factors that may become more apparent during the course of treatment. In the absence of severe symptoms requiring urgent intervention, fluid restriction (FR) is widely endorsed as the first-line treatment for SIAD in current guidelines, but there is considerable controversy regarding second-line therapy in instances where FR is unsuccessful, which occurs in around half of cases. We review the epidemiology, pathophysiology, and differential diagnosis of SIAD, and summarize recent evidence for therapeutic options beyond FR, with a focus on tolvaptan, urea, and sodium-glucose cotransporter 2 inhibitors.
Topics: Humans; Hyponatremia; Inappropriate ADH Syndrome; Water-Electrolyte Balance; Neoplasms
PubMed: 36974717
DOI: 10.1210/endrev/bnad010 -
Annual Review of Physiology Feb 2024The cytoplasm is densely packed with molecules that contribute to its nonideal behavior. Cytosolic crowding influences chemical reaction rates, intracellular water... (Review)
Review
The cytoplasm is densely packed with molecules that contribute to its nonideal behavior. Cytosolic crowding influences chemical reaction rates, intracellular water mobility, and macromolecular complex formation. Overcrowding is potentially catastrophic; to counteract this problem, cells have evolved acute and chronic homeostatic mechanisms that optimize cellular crowdedness. Here, we provide a physiology-focused overview of molecular crowding, highlighting contemporary advances in our understanding of its sensing and control. Long hypothesized as a form of crowding-induced microcompartmentation, phase separation allows cells to detect and respond to intracellular crowding through the action of biomolecular condensates, as indicated by recent studies. Growing evidence indicates that crowding is closely tied to cell size and fluid volume, homeostatic responses to physical compression and desiccation, tissue architecture, circadian rhythm, aging, transepithelial transport, and total body electrolyte and water balance. Thus, molecular crowding is a fundamental physiologic parameter that impacts diverse functions extending from molecule to organism.
Topics: Humans; Water-Electrolyte Balance; Water
PubMed: 37931170
DOI: 10.1146/annurev-physiol-042222-025920 -
Clinical Journal of the American... Nov 2023Prostaglandin E2 (PGE2) plays a physiological role in osmoregulation, a process that is affected early in autosomal dominant polycystic kidney disease (ADPKD). PGE2 has...
BACKGROUND
Prostaglandin E2 (PGE2) plays a physiological role in osmoregulation, a process that is affected early in autosomal dominant polycystic kidney disease (ADPKD). PGE2 has also been implicated in the pathogenesis of ADPKD in preclinical models, but human data are limited. Here, we hypothesized that urinary PGE2 excretion is associated with impaired osmoregulation, disease severity, and disease progression in human ADPKD.
METHODS
Urinary excretions of PGE2 and its metabolite (PGEM) were measured in a prospective cohort of patients with ADPKD. The associations between urinary PGE2 and PGEM excretions, markers of osmoregulation, eGFR and height-adjusted total kidney volume were assessed using linear regression models. Cox regression and linear mixed models were used for the longitudinal analysis of the associations between urinary PGE2 and PGEM excretions and disease progression defined as 40% eGFR loss or kidney failure, and change in eGFR over time. In two intervention studies, we quantified the effect of starting tolvaptan and adding hydrochlorothiazide to tolvaptan on urinary PGE2 and PGEM excretions.
RESULTS
In 562 patients with ADPKD (61% female, eGFR 63±28 ml/min per 1.73 m 2 ), higher urinary PGE2 or PGEM excretions were independently associated with higher plasma copeptin, lower urine osmolality, lower eGFR, and greater total kidney volume. Participants with higher baseline urinary PGE2 and PGEM excretions had a higher risk of 40% eGFR loss or kidney failure (hazard ratio, 1.28; 95% confidence interval [CI], 1.13 to 1.46 and hazard ratio, 1.50; 95% CI, 1.26 to 1.80 per two-fold higher urinary PGE2 or PGEM excretions) and a faster change in eGFR over time (-0.39 [95% CI, -0.59 to -0.20] and -0.53 [95% CI, -0.75 to -0.31] ml/min per 1.73 m 2 per year). In the intervention studies, urinary PGEM excretion was higher after starting tolvaptan, while urinary PGE2 excretion was higher after adding hydrochlorothiazide to tolvaptan.
CONCLUSIONS
Higher urinary PGE2 and PGEM excretions in patients with ADPKD are associated with impaired osmoregulation, disease severity, and progression.
Topics: Humans; Female; Male; Polycystic Kidney, Autosomal Dominant; Tolvaptan; Dinoprostone; Prospective Studies; Osmoregulation; Disease Progression; Kidney; Renal Insufficiency; Hydrochlorothiazide; Glomerular Filtration Rate; Antidiuretic Hormone Receptor Antagonists
PubMed: 37574650
DOI: 10.2215/CJN.0000000000000269 -
Current Opinion in Pediatrics Apr 2024This review highlights recent advances in understanding fluid and electrolyte homeostasis during the newborn period, including heightened recognition of fluid overload... (Review)
Review
PURPOSE OF REVIEW
This review highlights recent advances in understanding fluid and electrolyte homeostasis during the newborn period, including heightened recognition of fluid overload and acute kidney injury contributing to poor clinical outcomes. Particular attention is given towards the care of extremely preterm infants.
RECENT FINDINGS
Emerging data demonstrate (i) disproportionally large transepidermal water loss in the extremely preterm population, (ii) the relationship between postnatal weight loss (negative fluid balance) and improved outcomes, (iii) the frequency and negative effects of dysnatremias early in life, (iv) the role of sodium homeostasis in optimizing postnatal growth, and (v) the deleterious effects of fluid overload and acute kidney injury.
SUMMARY
As clinicians care for an increasing number of preterm infants, understanding progress in approaches to fluid and electrolyte management and avoidance of fluid overload states will improve the care and outcomes of this vulnerable population. Further translational and clinical studies are needed to address remaining knowledge gaps and improve current approaches to fluid and electrolyte management.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Water-Electrolyte Balance; Fluid Therapy; Acute Kidney Injury; Electrolytes
PubMed: 37962361
DOI: 10.1097/MOP.0000000000001308 -
Hypertension (Dallas, Tex. : 1979) Mar 2024Homeostasis of fluid and electrolytes is a tightly controlled physiological process. Failure of this process is a hallmark of hypertension, chronic kidney disease, heart... (Review)
Review
Homeostasis of fluid and electrolytes is a tightly controlled physiological process. Failure of this process is a hallmark of hypertension, chronic kidney disease, heart failure, and other acute and chronic diseases. While the kidney remains the major player in the control of whole-body fluid and electrolyte homeostasis, recent discoveries point toward more peripheral mechanisms leading to sodium storage in tissues, such as skin and muscle, and a link between this sodium and a range of diseases, including the conditions above. In this review, we describe multiple facets of sodium and fluid balance from traditional concepts to novel discoveries. We examine the differences between acute disruption of sodium balance and the longer term adaptation in chronic disease, highlighting areas that cannot be explained by a kidney-centric model alone. The theoretical and methodological challenges of more recently proposed models are discussed. We acknowledge the different roles of extracellular and intracellular spaces and propose an integrated model that maintains fluid and electrolyte homeostasis and can be distilled into a few elemental players: the microvasculature, the interstitium, and tissue cells. Understanding their interplay will guide a more precise treatment of conditions characterized by sodium excess, for which primary aldosteronism is presented as a prototype.
Topics: Humans; Sodium; Water-Electrolyte Balance; Kidney; Hypertension; Electrolytes; Chronic Disease
PubMed: 38084591
DOI: 10.1161/HYPERTENSIONAHA.123.19569 -
Annual Review of Entomology Jan 2024The rapid advances in available transcriptomic and genomic data and our understanding of the physiology and biochemistry of whitefly-plant interactions have allowed us... (Review)
Review
The rapid advances in available transcriptomic and genomic data and our understanding of the physiology and biochemistry of whitefly-plant interactions have allowed us to gain new and significant insights into the biology of whiteflies and their successful adaptation to host plants. In this review, we provide a comprehensive overview of the mechanisms that whiteflies have evolved to overcome the challenges of feeding on phloem sap. We also highlight the evolution and functions of gene families involved in host perception, evaluation, and manipulation; primary metabolism; and metabolite detoxification. We discuss the emerging themes in plant immunity to whiteflies, focusing on whitefly effectors and their sites of action in plant defense-signaling pathways. We conclude with a discussion of advances in the genetic manipulation of whiteflies and the potential that they hold for exploring the interactions between whiteflies and their host plants, as well as the development of novel strategies for the genetic control of whiteflies.
Topics: Animals; Hemiptera; Plants; Signal Transduction
PubMed: 37816261
DOI: 10.1146/annurev-ento-120120-093940 -
Handbook of Clinical Neurology 2024Migraine presents with high prevalence and similar clinical course with different disorders such as neurological, psychiatric, cardio- and cerebrovascular,... (Review)
Review
Migraine presents with high prevalence and similar clinical course with different disorders such as neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metabolic-endocrine, and immunological conditions, which can often cooccur themselves. Multifaceted mechanisms subtend these comorbidities with a bidirectional link. First, a shared genetic load can explain the cooccurrence. Second, comorbid pathologies can promote disproportionate energetic needs, thalamocortical network dysexcitability, and systemic transient or persistent proinflammatory state, which may trigger the activation of a broad self-protective network that includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This response results in maintenance of brain homeostasis by modulating subcortical-cortical excitability, energetic balance, osmoregulation, and emotional response. In this process, the CGRP is released in the trigeminovascular system. However, the calcitonin gene-related peptide (CGRP) plays several actions also outside the brain to maintain the homeostatic needs and is involved in the physiological functions of different systems, whose disorders are associated with migraine. This aspect further increases the complexity of migraine treatment, where standard therapies often have systemic adverse effects. On the other hand, some preventives can improve comorbid conditions. In summary, we propose that migraine management should involve a multidisciplinary approach to identify and mitigate potential risk factors and comorbidity and tailor therapies individually.
Topics: Humans; Calcitonin Gene-Related Peptide; Multimorbidity; Migraine Disorders; Brain; Neurosecretory Systems
PubMed: 38307670
DOI: 10.1016/B978-0-12-823357-3.00014-8 -
European Journal of Preventive... Oct 2023Fluid retention is a major determinant of symptoms in patients with heart failure (HF), and it is closely associated with prognosis. Hence, congestion represents a...
Fluid retention is a major determinant of symptoms in patients with heart failure (HF), and it is closely associated with prognosis. Hence, congestion represents a critical therapeutic target in this clinical setting. The first therapeutic strategy in HF patients with fluid overload is optimization of diuretic intervention to maximize water and sodium excretion. When diuretic therapy fails to relieve congestion, renal replacement therapy represents the only alternative option for fluid removal, as well as a way to restore diuretic responsiveness. On this background, the pathophysiology of fluid balance in HF is complex, with heart, kidney, and lung being deeply involved in volume regulation and management. Therefore, the interplay between these organs should be appreciated and considered when fluid overload in HF patients is targeted.
Topics: Humans; Heart Failure; Heart; Kidney; Water-Electrolyte Balance; Diuretics
PubMed: 37819223
DOI: 10.1093/eurjpc/zwad166