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JACC. Heart Failure Jan 2024
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Diabetes Mellitus, Type 2; Diuresis; Stroke Volume
PubMed: 37943224
DOI: 10.1016/j.jchf.2023.09.013 -
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 -
Current Drug Targets 2020Urea Transporters are a family of membrane channel proteins that facilitate the passive transport of urea across the plasma membrane. UTs are divided into two subgroups,... (Review)
Review
BACKGROUND
Urea Transporters are a family of membrane channel proteins that facilitate the passive transport of urea across the plasma membrane. UTs are divided into two subgroups, UT-A and UT-B. UT-As are primarily located in renal tubule epithelia and UT-Bs are highly expressed in renal descending vasa recta and extrarenal multiple tissues. Various urea transporter knockout mice exhibit low urine concentrating ability, which suggests that UTs are novel diuretic targets. With highthroughput screening of small molecule drug-like compound libraries, various potent UT inhibitors with IC50 at nanomolar level were identified. Furthermore, selective UT inhibitors exhibit diuretic activity without disturbing electrolyte and metabolism balance, which confirms the potential of UTs as diuretic targets and UT inhibitors as novel diuretics that do not cause electrolyte imbalance.
OBJECTIVE
This review article summarizes the identification and validation of urea transporter as a potential diuretic target and the discovery of small molecule UT inhibitors as a novel type of diuretics.
CONCLUSION
UTs are a potential diuretic target. UT inhibitors play significant diuresis and can be developed to diuretics without disturbing electrolyte balance.
Topics: Animals; Cell Line; Diuresis; Diuretics; Humans; Membrane Transport Proteins; Mice; Mice, Knockout; Small Molecule Libraries; Structure-Activity Relationship; Urea; Water-Electrolyte Balance; Urea Transporters
PubMed: 31782365
DOI: 10.2174/1389450120666191129101915 -
Surgical Laparoscopy, Endoscopy &... Oct 2022Feeding a ventral hernia repair (VHR) patient before the return of bowel function (ROBF) can lead to distention and emesis. Many patients spontaneously diurese after...
PURPOSE
Feeding a ventral hernia repair (VHR) patient before the return of bowel function (ROBF) can lead to distention and emesis. Many patients spontaneously diurese after surgery. We hypothesized that this auto-diuresis would signal ROBF.
MATERIALS AND METHODS
A total of 395 patients who underwent open, laparoscopic, or mixed VHR were evaluated for correlation between fluid status and ROBF or discharge. ROBF within 24 hours and discharge within 24 hours or 48 hours were used as outcome measures.
RESULTS
Patients remained an average 3.59 days after surgery in the hospital and the average ROBF was on day 2.99. The first shift of ≥700 mL of urine predicted ROBF ( P =0.03) and discharge ( P =0.04) within 24 hours. The first shift output of ≥500 mL predicted discharge within 48 hours ( P =0.02).
CONCLUSION
Auto-diuresis after surgery is correlated to ROBF and discharge. Accurate fluid measurement can predict bowel function and allow early diet and discharge.
Topics: Diuresis; Hernia, Ventral; Herniorrhaphy; Humans; Laparoscopy; Retrospective Studies
PubMed: 35960701
DOI: 10.1097/SLE.0000000000001083 -
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 -
La Revue de Medecine Interne May 2023Post-Obstructive Diuresis (POD) is a polyuria that occurs following the release of an obstruction from the urinary tract that prevents the flow of urine. POD requires... (Review)
Review
Post-Obstructive Diuresis (POD) is a polyuria that occurs following the release of an obstruction from the urinary tract that prevents the flow of urine. POD requires prompt diagnosis to avoid complications. Although its pathophysiology is better understood, there is little scientific evidence for its treatment. Restoration of renal homeostasis requires correction of blood volume and electrolyte disturbances to prevent complications, which can be serious. In this article, we propose a synthesis of knowledge on the subject, as well as a management strategy.
Topics: Humans; Diuresis; Kidney; Polyuria; Physicians
PubMed: 36764894
DOI: 10.1016/j.revmed.2023.01.011 -
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 -
Neurourology and Urodynamics Jun 2024This article delves into the intricate relationship between kidney function, diuresis, and lower urinary tract symptoms (LUTS) throughout the transitions of the human... (Review)
Review
INTRODUCTION
This article delves into the intricate relationship between kidney function, diuresis, and lower urinary tract symptoms (LUTS) throughout the transitions of the human lifespan. It explores circadian regulation of urine production, maturation of renal function from birth to adulthood, and effects of aging on kidney function and LUTS. The complex connections between these factors are highlighted, offering insights into potential interventions and personalized management strategies.
METHODS
An international panel of seven experts engaged in online discussions, focusing on kidney function, diuresis, and LUTS throughout life. This manuscript summarizes expert insights, literature reviews, and findings presented during a webinar and subsequent discussions.
RESULTS
Renal function undergoes significant maturation from birth to adulthood, with changes in glomerular filtration rate, diuresis, and tubular function. A circadian rhythm in urine production is established during childhood. Adolescents and young adults can experience persistent enuresis due to lifestyle factors, comorbidities, and complex physiological changes. In older adults, age-related alterations in kidney function disrupt the circadian rhythm of diuresis, contributing to nocturnal polyuria and LUTS.
CONCLUSION
The interplay between kidney function, diuresis, and LUTS is crucial in understanding lifelong urinary health. Bridging the gap between pediatric and adult care is essential to address enuresis in adolescents and young adults effectively. For older adults, recognizing the impact of aging on renal function and fluid balance is vital in managing nocturia. This holistic approach provides a foundation for developing innovative interventions and personalized treatments to enhance quality of life for individuals with LUTS across all stages of life.
Topics: Adolescent; Adult; Humans; Aging; Circadian Rhythm; Diuresis; Kidney; Lower Urinary Tract Symptoms; Young Adult; Middle Aged
PubMed: 37846751
DOI: 10.1002/nau.25308