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Cardiorenal Medicine 2024Increased renal sodium avidity is a hallmark feature of the heart failure syndrome. (Review)
Review
BACKGROUND
Increased renal sodium avidity is a hallmark feature of the heart failure syndrome.
SUMMARY
Increased renal sodium avidity refers to the inability of the kidneys to elicit potent natriuresis in response to sodium loading. This eventually causes congestion, which is a major contributor to hospital admissions and mortality in heart failure.
KEY MESSAGES
Important novel concepts such as the renal tamponade hypothesis, accelerated nephron loss, and the role of hypochloremia, the sympathetic nervous system, inflammation, the lymphatic system, and interstitial sodium buffers are involved in the pathophysiology of renal sodium avidity. A good understanding of these concepts is crucially important with respect to treatment recommendations regarding dietary sodium restriction, fluid restriction, rapid up-titration of guideline-directed medical therapies, combination diuretic therapy, natriuresis-guided diuretic therapy, use of hypertonic saline, and ultrafiltration.
Topics: Humans; Heart Failure; Sodium; Kidney; Natriuresis; Diuretics; Cardio-Renal Syndrome
PubMed: 38565080
DOI: 10.1159/000538601 -
Circulation. Heart Failure Jul 2020
Topics: Heart Failure; Humans; Inflammation; Natriuresis; Natriuretic Peptides; Vasodilator Agents
PubMed: 32611204
DOI: 10.1161/CIRCHEARTFAILURE.120.007208 -
American Journal of Hypertension Aug 2020Salt (NaCl) is a prerequisite for life. Excessive intake of salt, however, is said to increase disease risk, including hypertension, arteriosclerosis, heart failure,... (Review)
Review
Salt (NaCl) is a prerequisite for life. Excessive intake of salt, however, is said to increase disease risk, including hypertension, arteriosclerosis, heart failure, renal disease, stroke, and cancer. Therefore, considerable research has been expended on the mechanism of sodium handling based on the current concepts of sodium balance. The studies have necessarily relied on relatively short-term experiments and focused on extremes of salt intake in humans. Ultra-long-term salt balance has received far less attention. We performed long-term salt balance studies at intakes of 6, 9, and 12 g/day and found that although the kidney remains the long-term excretory gate, tissue and plasma sodium concentrations are not necessarily the same and that urinary salt excretion does not necessarily reflect total-body salt content. We found that to excrete salt, the body makes a great effort to conserve water, resulting in a natriuretic-ureotelic principle of salt excretion. Of note, renal sodium handling is characterized by osmolyte excretion with anti-parallel water reabsorption, a state-of-affairs that is achieved through the interaction of multiple organs. In this review, we discuss novel sodium and water balance concepts in reference to our ultra-long-term study. An important key to understanding body sodium metabolism is to focus on water conservation, a biological principle to protect from dehydration, since excess dietary salt excretion into the urine predisposes to renal water loss because of natriuresis. We believe that our research direction is relevant not only to salt balance but also to cardiovascular regulatory mechanisms.
Topics: Animals; Appetite; Body Water; Cardiovascular System; Drinking; Energy Metabolism; Humans; Infradian Rhythm; Kidney; Kidney Concentrating Ability; Liver; Muscle, Skeletal; Natriuresis; Renal Elimination; Sodium; Sodium Chloride, Dietary; Thirst; Water-Electrolyte Balance
PubMed: 32198504
DOI: 10.1093/ajh/hpaa049 -
The Journal of Pharmacology and... Aug 20228-Aminoguanine and 8-aminoguanosine (via metabolism to 8-aminoguanine) are endogenous 8-aminopurines that induce diuresis, natriuresis, and glucosuria by inhibiting...
8-Aminoguanine and 8-aminoguanosine (via metabolism to 8-aminoguanine) are endogenous 8-aminopurines that induce diuresis, natriuresis, and glucosuria by inhibiting purine nucleoside phosphorylase (PNPase); moreover, both 8-aminopurines cause antikaliuresis by other mechanisms. Because 8-aminoinosine and 8-aminohypoxanthine are structurally similar to 8-aminoguanosine and 8-aminoguanine, respectively, we sought to define their renal excretory effects. First, we compared the ability of 8-aminoguanine, 8-aminohypoxanthine, and 8-aminoinosine to inhibit recombinant PNPase. These compounds inhibited PNPase with a potency order of 8-aminoguanine > 8-aminohypoxanthine = 8-aminoinosine. Additional studies showed that 8-aminoinosine is a competitive substrate that is metabolized to a competitive PNPase inhibitor, namely 8-aminohypoxanthine. Administration of each 8-aminopurine (33.5 µmol/kg) reduced the guanine-to-guanosine and hypoxanthine-to-inosine ratios in urine, a finding confirming their ability to inhibit PNPase in vivo. All three 8-aminopurines induced diuresis, natriuresis, and glucosuria; however, the glucosuric effects of 8-aminohypoxanthine and 8-aminoinosine were less pronounced than those of 8-aminoguanine. Neither 8-aminohypoxanthine nor 8-aminoinosine altered potassium excretion, whereas 8-aminoguanine caused antikaliuresis. In vivo administration of 8-aminoinosine increased 8-aminohypoxanthine excretion, indicating that 8-aminohypoxanthine mediates, in part, the effects of 8-aminoinosine. Finally, 8-aminohypoxanthine was metabolized to 8-aminoxanthine by xanthine oxidase. Using ultraperformance liquid chromatography-tandem mass spectrometry, we identified 8-aminoinosine as an endogenous 8-aminopurine. In conclusion, 8-aminopurines have useful pharmacological profiles. To induce diuresis, natriuresis, glucosuria, and antikaliuresis, 8-aminoguanine (or its prodrug 8-aminoguanosine) would be preferred. If only diuresis and natriuresis, without marked glucosuria or antikaliuresis, is desired, 8-aminohypoxanthine or 8-aminoinosine might be useful. Finally, here we report the in vivo existence of another pharmacologically active 8-aminopurine, namely 8-aminoinosine. SIGNIFICANCE STATEMENT: Here, we report that a family of 8-aminopurines affects renal excretory function: effects that may be useful for treating multiple diseases including hypertension, heart failure, and chronic kidney disease. For diuresis and natriuresis accompanied by glucosuria and antikaliuresis, 8-aminoguanine (or its prodrug 8-aminoguanosine) would be useful; if only diuresis and natriuresis is called for, 8-aminohypoxanthine or 8-aminoinosine would be useful. Previously, we identified 8-aminoguanine and 8-aminoguanosine as endogenous 8-aminopurines; here, we extend the family of endogenous 8-aminopurines to include 8-aminoinosine.
Topics: Humans; Diuresis; Diuretics; Glycosuria; Natriuresis; Prodrugs; Purine-Nucleoside Phosphorylase
PubMed: 35609923
DOI: 10.1124/jpet.122.001221 -
Journal of Nephrology Mar 2024Cystinuria is a rare genetic kidney stone disease, with no cure. Current treatments involve lowering urinary cystine levels and increasing cystine solubility. This... (Review)
Review
BACKGROUND
Cystinuria is a rare genetic kidney stone disease, with no cure. Current treatments involve lowering urinary cystine levels and increasing cystine solubility. This systematic review evaluates the available literature regarding non-surgical interventions for cystinuria.
METHODS
Key electronic databases were searched for studies that described the clinical management of cystinuria with high diuresis, alkalinizing agents and thiol-based drugs that were published between 2000 and 2022. Observational studies were included if they contained clinical investigation with at least one previous or current episode of cystine stones, urine cystine levels > 250 mg/L and patients being managed with urinary dilution, alkalinizing agents or other pharmacological agents. All included studies were assessed for study design, patient characteristics and outcomes. A qualitative and critical analysis was performed whereby study quality was assessed using Methodological Index for Non-Randomized Studies (MINORS). Two authors performed the quality assessment and excluded the studies with a low MINORS score.
RESULTS
Fourteen studies met the review inclusion and quality criteria. Of the fourteen studies, two reported treatment using alkalinizing agents, six reported treatment using thiol-based drugs, and six reported combination treatment using alkalinizing agents and thiol-based drugs. These studies indicated that first-line therapies, including high fluid intake and urinary alkalinization, increased urine volume to > 3 L/day and urinary pH > 7.0, and were associated with reduced urinary cystine levels and cystine stone formation. Second-line therapy with cystine-binding thiol drugs, such as tiopronin and D-penicillamine, reduced urinary cystine levels, cystine crystal volume and increased cystine solubility, resulting in decreased cystine stone formation and stone recurrence rate. Further, combined intervention with alkalinizing agents and thiol-based drugs synergistically reduced stone recurrence.
CONCLUSION
Cystinuria treatment may require a combined approach of high diuresis, alkalinization and pharmacological interventions with regular monitoring of urinary pH, cystine levels, cystine crystal volume and solubility. However, poor adherence to treatment is relatively frequent, hence the pressing urgency for improved therapies and treatments.
Topics: Cystinuria; Humans; Cystine; Sulfhydryl Compounds; Treatment Outcome; Diuresis
PubMed: 37957454
DOI: 10.1007/s40620-023-01795-6 -
F1000Research 2020This narrative review investigates the effect of dietary intake on nocturnal voiding severity. The primary aims of this review are to provide a framework for future... (Review)
Review
This narrative review investigates the effect of dietary intake on nocturnal voiding severity. The primary aims of this review are to provide a framework for future research and ultimately contribute to more comprehensive, lifestyle-centered guidelines for the management of nocturia. A literature search was conducted in Web of Science, PubMed, and Google Scholar databases using the keywords "nocturia", "diuresis", "natriuresis", "food", "diet", and "nutrients". High fruit and vegetable consumption was negatively associated with nocturia. High intake of tea and dietary sodium showed a positive association with nocturia. Several foods have also been directly linked to changes in diuresis rate, glycemic control, and endogenous serum melatonin concentration, offering potential mechanisms for this observed effect. Overall quality of the evidence was low. At present, there is limited evidence to suggest that certain foods, electrolytes, and specific compounds may contribute to the pathogenesis of nocturia. A greater understanding of the impact of food and nutrients on body fluid metabolism is needed to further refine the evaluation and treatment of nocturia.
Topics: Diet; Food; Humans; Life Style; Nocturia
PubMed: 32185022
DOI: 10.12688/f1000research.21466.1 -
Internal Medicine (Tokyo, Japan) Dec 2022Ebstein's anomaly is an uncommon congenital disorder affecting the tricuspid valve. We herein report a 38-year-old woman who experienced consciousness and sensory...
Ebstein's anomaly is an uncommon congenital disorder affecting the tricuspid valve. We herein report a 38-year-old woman who experienced consciousness and sensory disturbance during treatment for heart failure caused by Ebstein's anomaly. Urgent magnetic resonance imaging and cerebral angiography demonstrated acute cerebral infarction and internal carotid artery obstruction with the development of collateral arteries. We diagnosed her with multiple cerebral infarctions due to moyamoya disease. Ebstein's anomaly concomitant with moyamoya disease is extremely rare. However, we should consider the possibility of this rare but important concurrence when treating patients with heart failure due to Ebstein's anomaly to avoid excessive diuresis and vasodilation and irreversible brain injury.
Topics: Female; Humans; Adult; Ebstein Anomaly; Moyamoya Disease; Tricuspid Valve; Heart Failure
PubMed: 35569986
DOI: 10.2169/internalmedicine.9516-22 -
Frontiers in Insect Science 2023, a major vector of Chagas disease, may be considered the model upon which the foundations of insect physiology and biochemistry were built. It is an obligate blood... (Review)
Review
, a major vector of Chagas disease, may be considered the model upon which the foundations of insect physiology and biochemistry were built. It is an obligate blood feeder in which the blood meal triggers growth, development and reproduction. The blood meal also triggers a post-prandial diuresis to maintain osmotic homeostasis. In , as with other insects, the Malpighian tubules play a critical role in this diuresis, and much has been learned about diuresis in , and in other model insects. But the post-genomic era has brought new insights, identifying functions quite apart from diuresis for Malpighian tubules. Indeed, microarrays, transcriptomes, and proteomics have revealed the major roles that Malpighian tubules play in immunity, detoxification, pesticide resistance, and in tolerance to overall stress. This is particularly relevant to since gorging on blood creates several challenges in addition to osmotic balance. Xenobiotics may be present in the blood or toxins may be produced by metabolism of blood; and these must be neutralized and excreted. These processes have not been well described at the molecular level for Malpighian tubules of This paper will review the involvement of Malpighian tubules in immunity and detoxification, identifying new aspects for Malpighian tubule physiology of by virtue of a transcriptome analysis. The transcriptome analysis indicates the potential of Malpighian tubules of to mount a robust innate immune response, and to contribute to antioxidant production and heme detoxification.
PubMed: 38469518
DOI: 10.3389/finsc.2023.1167889 -
Physiological Reviews Jul 2020Autocrine and paracrine signaling in the kidney adds an extra level of diversity and complexity to renal physiology. The extensive scientific production on the topic... (Review)
Review
Autocrine and paracrine signaling in the kidney adds an extra level of diversity and complexity to renal physiology. The extensive scientific production on the topic precludes easy understanding of the fundamental purpose of the vast number of molecules and systems that influence the renal function. This systematic review provides the broader pen strokes for a collected image of renal paracrine signaling. First, we recapitulate the essence of each paracrine system one by one. Thereafter the single components are merged into an overarching physiological concept. The presented survey shows that despite the diversity in the web of paracrine factors, the collected effect on renal function may not be complicated after all. In essence, paracrine activation provides an intelligent system that perceives minor perturbations and reacts with a coordinated and integrated tissue response that relieves the work load from the renal epithelia and favors diuresis and natriuresis. We suggest that the overall function of paracrine signaling is reno-protection and argue that renal paracrine signaling and self-regulation are two sides of the same coin. Thus local paracrine signaling is an intrinsic function of the kidney, and the overall renal effect of changes in blood pressure, volume load, and systemic hormones will always be tinted by its paracrine status.
Topics: Animals; Autocrine Communication; Humans; Kidney; Paracrine Communication; Signal Transduction
PubMed: 31999508
DOI: 10.1152/physrev.00014.2019