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American Journal of Obstetrics and... Feb 2022High blood pressure in the postpartum period is most commonly seen in women with antenatal hypertensive disorders, but it can develop de novo in the postpartum time... (Review)
Review
High blood pressure in the postpartum period is most commonly seen in women with antenatal hypertensive disorders, but it can develop de novo in the postpartum time frame. Whether postpartum preeclampsia or eclampsia represents a separate entity from preeclampsia or eclampsia with antepartum onset is unclear. Although definitions vary, the diagnosis of postpartum preeclampsia should be considered in women with new-onset hypertension 48 hours to 6 weeks after delivery. New-onset postpartum preeclampsia is an understudied disease entity with few evidence-based guidelines to guide diagnosis and management. We propose that new-onset hypertension with the presence of any severe features (including severely elevated blood pressure in women with no history of hypertension) be referred to as postpartum preeclampsia after exclusion of other etiologies to facilitate recognition and timely management. Older maternal age, black race, maternal obesity, and cesarean delivery are all associated with a higher risk of postpartum preeclampsia. Most women with delayed-onset postpartum preeclampsia present within the first 7 to 10 days after delivery, most frequently with neurologic symptoms, typically headache. The cornerstones of treatment include the use of antihypertensive agents, magnesium, and diuresis. Postpartum preeclampsia may be associated with a higher risk of maternal morbidity than preeclampsia with antepartum onset, yet it remains an understudied disease process. Future research should focus on the pathophysiology and specific risk factors. A better understanding is imperative for patient care and counseling and anticipatory guidance before hospital discharge and is important for the reduction of maternal morbidity and mortality in the postpartum period.
Topics: Anticonvulsants; Antihypertensive Agents; Blood Pressure Monitoring, Ambulatory; Diuresis; Eclampsia; Female; Humans; Magnesium Sulfate; Pre-Eclampsia; Pregnancy; Puerperal Disorders; Risk Factors
PubMed: 35177218
DOI: 10.1016/j.ajog.2020.10.027 -
Medecine Sciences : M/S May 2016Caffeine is an alkaloid which belongs to the family of methylxanthines and is present in beverages, food and drugs. Caffeine competitively antagonizes the adenosine... (Review)
Review
Caffeine is an alkaloid which belongs to the family of methylxanthines and is present in beverages, food and drugs. Caffeine competitively antagonizes the adenosine receptors (AR), which are G protein-coupled receptors largely distributed throughout the body, including brain, heart, vessels and kidneys. Caffeine consumption has a well-known diuretic effect. The homeostasis of salt and water involves different segments of the nephron, in which adenosine plays complex roles depending on the differential expression of AR. Hence, caffeine increases glomerular filtration rate by opposing the vasoconstriction of renal afferent arteriole mediated by adenosine via type 1 AR during the tubuloglomerular feedback. Caffeine also inhibits Na(+) reabsorption at the level of renal proximal tubules. In addition, caffeine perturbs the hepatorenal reflex via sensory nerves in Mall's intrahepatic spaces. Here, we review the physiology of caffeine-induced natriuresis and diuresis, as well as the putative pathological implications.
Topics: Adenosine; Animals; Caffeine; Diuresis; Diuretics; Humans; Kidney Tubules; Receptors, Purinergic P1; Signal Transduction; Sodium
PubMed: 27225921
DOI: 10.1051/medsci/20163205015 -
Heart Failure Reviews May 2021Heart failure (HF) continues to be a serious public health challenge despite significant advancements in therapeutics and is often complicated by multiple other... (Review)
Review
Heart failure (HF) continues to be a serious public health challenge despite significant advancements in therapeutics and is often complicated by multiple other comorbidities. Of particular concern is type 2 diabetes mellitus (T2DM) which not only amplifies the risk, but also limits the treatment options available to patients. The sodium-glucose linked cotransporter subtype 2 (SGLT2)-inhibitor class, which was initially developed as a treatment for T2DM, has shown great promise in reducing cardiovascular risk, particularly around HF outcomes - regardless of diabetes status.There are ongoing efforts to elucidate the true mechanism of action of this novel drug class. Its primary mechanism of inducing glycosuria and diuresis from receptor blockade in the renal nephron seems unlikely to be responsible for the rapid and striking benefits seen in clinical trials. Early mechanistic work around conventional therapeutic targets seem to be inconclusive. There are some emerging theories around its effect on myocardial energetics and calcium balance as well as on renal physiology. In this review, we discuss some of the cutting-edge hypotheses and concepts currently being explored around this drug class in an attempt better understand the molecular mechanics of this novel agent.
Topics: Diabetes Mellitus, Type 2; Diuresis; Glycosuria; Humans; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33274396
DOI: 10.1007/s10741-020-10038-w -
Journal of the American Society of... Oct 2018In the past, the treatment of autosomal dominant polycystic kidney disease (ADPKD) has been limited to the management of its symptoms and complications. Recently, the US... (Review)
Review
In the past, the treatment of autosomal dominant polycystic kidney disease (ADPKD) has been limited to the management of its symptoms and complications. Recently, the US Food and Drug Administration (FDA) approved tolvaptan as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing ADPKD. Full prescribing information approved by the FDA provides helpful guidelines but does not address practical questions that are being raised by nephrologists, internists, and general practitioners taking care of patients with ADPKD, and by the patients themselves. In this review, we provide practical guidance and discuss steps that require consideration before and after prescribing tolvaptan to patients with ADPKD to ensure that this treatment is implemented safely and effectively. These steps include confirmation of diagnosis; identification of rapidly progressive disease; implementation of basic renal protective measures; counseling of patients on potential benefits and harms; exclusions to use; education of patients on aquaresis and its expected consequences; initiation, titration, and optimization of tolvaptan treatment; prevention of aquaresis-related complications; evaluation and management of liver enzyme elevations; and monitoring of treatment efficacy. Our recommendations are made on the basis of published evidence and our collective experiences during the randomized, clinical trials and open-label extension studies of tolvaptan in ADPKD.
Topics: Algorithms; Antidiuretic Hormone Receptor Antagonists; Clinical Protocols; Dehydration; Disease Progression; Diuresis; Female; Glomerular Filtration Rate; Humans; Liver; Magnetic Resonance Imaging; Male; Patient Selection; Polycystic Kidney, Autosomal Dominant; Time Factors; Tolvaptan; Treatment Outcome
PubMed: 30228150
DOI: 10.1681/ASN.2018060590 -
American Family Physician Mar 2015Hyponatremia and hypernatremia are common findings in the inpatient and outpatient settings. Sodium disorders are associated with an increased risk of morbidity and...
Hyponatremia and hypernatremia are common findings in the inpatient and outpatient settings. Sodium disorders are associated with an increased risk of morbidity and mortality. Plasma osmolality plays a critical role in the pathophysiology and treatment of sodium disorders. Hyponatremia and hypernatremia are classified based on volume status (hypovolemia, euvolemia, and hypervolemia). Sodium disorders are diagnosed by findings from the history, physical examination, laboratory studies, and evaluation of volume status. Treatment is based on symptoms and underlying causes. In general, hyponatremia is treated with fluid restriction (in the setting of euvolemia), isotonic saline (in hypovolemia), and diuresis (in hypervolemia). A combination of these therapies may be needed based on the presentation. Hypertonic saline is used to treat severe symptomatic hyponatremia. Medications such as vaptans may have a role in the treatment of euvolemic and hypervolemic hyponatremia. The treatment of hypernatremia involves correcting the underlying cause and correcting the free water deficit.
Topics: Diagnosis, Differential; Diuresis; Fluid Therapy; Humans; Hypernatremia; Hyponatremia; Isotonic Solutions; Saline Solution, Hypertonic; Sodium
PubMed: 25822386
DOI: No ID Found -
Urology Nov 2019Nocturnal polyuria (NP), characterized by overproduction of urine at night (greater than 20%-33% of total 24-hour urine volume depending on age), is a major contributing... (Review)
Review
Nocturnal polyuria (NP), characterized by overproduction of urine at night (greater than 20%-33% of total 24-hour urine volume depending on age), is a major contributing factor in most nocturia cases. Nocturia can be caused by intake, urological, nephrological, hormonal, sleep, and cardiovascular factors. It is therefore important to accurately diagnose both the type of nocturia and the potentially associated medical conditions to determine appropriate treatment. Diagnostic tools, in addition to a thorough history and physical examination, include voiding/bladder diary analyses and questionnaires to diagnose nocturia type (NP, diminished nocturnal/global bladder capacity, global polyuria) and causative factors. Lifestyle modifications are the first intervention implemented for the management of nocturia and NP but, as symptoms progress, such measures may be insufficient, and pharmacotherapy may be initiated. While drugs for benign prostatic hyperplasia and overactive bladder have demonstrated statistically significant reductions in nocturnal voids, patients often fail to achieve a clinically meaningful response. Antidiuretic treatment is warranted for patients with nocturia due to NP because, in many patients, it treats the underlying cause (ie, insufficient secretion of antidiuretic hormone arginine vasopressin) that leads to overproduction of urine at night and has been shown to provide statistically significant reductions in nocturnal voids. Desmopressin, a synthetic analog of arginine vasopressin, is the only antidiuretic treatment indicated specifically for nocturia due to NP. Overall, the pathophysiology of NP is complex and differs from that of other types of nocturia. A multidisciplinary approach is necessary to effectively diagnose and manage this bothersome condition.
Topics: Diuresis; Humans; Nocturia; Polyuria; Treatment Outcome
PubMed: 31586470
DOI: 10.1016/j.urology.2019.09.022 -
Circulation Research May 2019Acute kidney injury (AKI) has a high prevalence and mortality in critically ill patients. It is also a powerful risk factor for heart failure incidence driven by...
RATIONALE
Acute kidney injury (AKI) has a high prevalence and mortality in critically ill patients. It is also a powerful risk factor for heart failure incidence driven by hemodynamic changes and neurohormonal activation. However, no drugs have been approved by the Food and Drug Administration. Endogenous pGC-A (particulate guanylyl cyclase A receptor) activators were reported to preserve renal function and improve mortality in AKI patients, although hypotension accompanied by pGC-A activators have limited their therapeutic potential.
OBJECTIVE
We investigated the therapeutic potential of a nonhypotensive pGC-A activator/designer natriuretic peptide, CRRL269, in a short-term, large animal model of ischemia-induced AKI and also investigated the potential of uCNP (urinary C-type natriuretic peptide) as a biomarker for AKI.
METHODS AND RESULTS
We first showed that CRRL269 stimulated cGMP generation, suppressed plasma angiotensin II, and reduced cardiac filling pressures without lowering blood pressure in the AKI canine model. We also demonstrated that CRRL269 preserved glomerular filtration rate, increased renal blood flow, and promoted diuresis and natriuresis. Further, CRRL269 reduced kidney injury and apoptosis as evidenced by ex vivo histology and tissue apoptosis analysis. We also showed, compared with native pGC-A activators, that CRRL269 is a more potent inhibitor of apoptosis in renal cells and induced less decreases in intracellular Ca concentration in vascular smooth muscle cells. The renal antiapoptotic effects were at least mediated by cGMP/PKG pathway. Further, CRRL269 inhibited proapoptotic genes expression using a polymerase chain reaction gene array. Additionally, we demonstrated that AKI increased uCNP levels.
CONCLUSIONS
Our study supports developing CRRL269 as a novel renocardiac protective agent for AKI treatment.
Topics: Acute Kidney Injury; Angiotensin II; Animals; Apoptosis; Biomarkers; Blood Pressure; Cyclic GMP; Diuresis; Dogs; Glomerular Filtration Rate; Male; Natriuresis; Natriuretic Peptide, C-Type; Natriuretic Peptides; Receptors, Atrial Natriuretic Factor; Renal Agents; Renal Circulation
PubMed: 30929579
DOI: 10.1161/CIRCRESAHA.118.314164 -
European Heart Journal Oct 2023In the ADVOR trial, acetazolamide improved decongestion in acute decompensated heart failure (ADHF). Whether the beneficial effects of acetazolamide are consistent... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
In the ADVOR trial, acetazolamide improved decongestion in acute decompensated heart failure (ADHF). Whether the beneficial effects of acetazolamide are consistent across the entire range of renal function remains unclear.
METHODS
This is a pre-specified analysis of the ADVOR trial that randomized 519 patients with ADHF to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The main endpoints of decongestion, diuresis, natriuresis, and clinical outcomes are assessed according to baseline renal function. Changes in renal function are evaluated between treatment arms.
RESULTS
On admission, median estimated glomerular filtration rate (eGFR) was 40 (30-52) mL/min/1.73 m². Acetazolamide consistently increased the likelihood of decongestion across the entire spectrum of eGFR (P-interaction = .977). Overall, natriuresis and diuresis were higher with acetazolamide, with a higher treatment effect for patients with low eGFR (both P-interaction < .007). Acetazolamide was associated with a higher incidence of worsening renal function (WRF; rise in creatinine ≥ 0.3 mg/dL) during the treatment period (40.5% vs. 18.9%; P < .001), but there was no difference in creatinine after 3 months (P = .565). This was not associated with a higher incidence of heart failure hospitalizations and mortality (P-interaction = .467). However, decongestion at discharge was associated with a lower incidence of adverse clinical outcomes irrespective of the onset of WRF (P-interaction = .805).
CONCLUSIONS
Acetazolamide is associated with a higher rate of successful decongestion across the entire range of renal function with more pronounced effects regarding natriuresis and diuresis in patients with a lower eGFR. While WRF occurred more frequently with acetazolamide, this was not associated with adverse clinical outcomes.
CLINICALTRIALS.GOV IDENTIFIER
NCT03505788.
Topics: Humans; Acetazolamide; Creatinine; Heart Failure; Diuresis; Kidney; Acute Disease
PubMed: 37623428
DOI: 10.1093/eurheartj/ehad557 -
Circulation Jul 2022Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear.
METHODS
In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide).
RESULTS
Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; =0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6-27.7]; =0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; =0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; =0.975; and urinary α1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; =0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (-1861 versus -727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83-0.95]; <0.001). There were no differences in the incidence of safety events between groups.
CONCLUSIONS
Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT04049045.
Topics: Humans; Benzhydryl Compounds; Creatinine; Diuresis; Diuretics; Glucosides; Heart Failure; Kidney; Prospective Studies; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35766022
DOI: 10.1161/CIRCULATIONAHA.122.059038 -
Hypertension (Dallas, Tex. : 1979) Jan 2017Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6- and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan was associated with a significant increase in natriuresis (adjusted treatment difference: 24.5 mmol/6 hours, 50.3 mmol/24 hours, both P<0.001) and diuresis (adjusted treatment difference: 291.2 mL/6 hours, P<0.001; 356.4 mL/24 hours, P=0.002) on day 1, but not on day 28, and greater reductions in office and ambulatory blood pressure on day 28. Despite morning dosing of both drugs, ambulatory blood pressure reductions were more pronounced at nighttime than at daytime or the 24-hour average. Compared with valsartan, sacubitril/valsartan significantly reduced N-terminal pro B-type natriuretic peptide levels on day 28 (adjusted treatment difference: -20%; P=0.001). Sacubitril/valsartan and valsartan were safe and well tolerated with no significant changes in body weight or serum sodium and potassium levels with either treatments. In conclusion, sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulatory blood pressure control, and significantly reduced N-terminal pro B-type natriuretic peptide levels in Asian patients with SSH.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01681576.
Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Blood Pressure; Cross-Over Studies; Diuresis; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Peptide Fragments; Sodium Chloride, Dietary; Tetrazoles; Time Factors; Valsartan
PubMed: 27849566
DOI: 10.1161/HYPERTENSIONAHA.116.08484