scholarly journals Emergence of Chloride as an Overlooked Cardiorenal Connector in Heart Failure

2019 ◽  
Vol 49 (1-2) ◽  
pp. 219-221 ◽  
Author(s):  
Amir Kazory ◽  
Claudio Ronco
Keyword(s):  
Heart Failure ◽  
Cardiorenal Syndrome ◽  
Adverse Outcomes ◽  
Diuretic Resistance ◽  
Regulatory Pathways ◽  
Serum Chloride ◽  
Wide Range ◽  
Advanced Stages ◽  
Renal Tubular

Several studies have recently challenged the sodium-centric view that has been dominating the field of heart failure (HF) and cardiorenal syndrome. The previously observed benefits of severe dietary restriction of salt do not seem to be consistently reproduced by contemporary studies. Moreover, there is evidence that too low intake may paradoxically lead to adverse outcomes in more advanced stages of HF. Facing the escalating controversy, investigators have shifted their focus from sodium to its often overlooked counter ion in salt, the chloride. Emerging data suggest that serum chloride levels could portend robust independent prognostic value in a wide range of HF syndromes possibly stronger than that of sodium. The untoward impact of hypochloremia on the outcomes could be mechanistically linked to renal tubular regulatory pathways, neurohormonal activation, and diuretic resistance. As such, it can be a potential target of therapy in this setting. In this article, the authors provide a brief overview of the role of serum chloride as a cardiorenal connector and explore the context in which the contemporary data should be interpreted. Implementation of predictive and therapeutic strategies incorporating the emerging evidence would be refined through discussion of nuances of such findings as well as their biological and clinical relevance.

scholarly journals The Role of Serum Chloride in Acute and Chronic Heart Failure: A Narrative Review

2021 ◽  
Vol 11 (2) ◽  
pp. 87-98
Author(s):  
Frederick Berro Rivera ◽  
Pia Alfonso ◽  
Jem Marie Golbin ◽  
Kevin Lo ◽  
Edgar Lerma ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chloride Channel ◽  
Chloride Channels ◽  
Prognostic Value ◽  
Diuretic Therapy ◽  
Juxtaglomerular Apparatus ◽  
Sodium Chloride Cotransporter ◽  
Serum Chloride ◽  
And Function

Clinical guidelines include diuretics for the treatment of heart failure (HF), not to decrease mortality but to decrease symptoms and hospitalizations. More attention has been paid to the worse outcomes, including mortality, associated with continual diuretic therapy due to hypochloremia. Studies have revealed a pivotal role for serum chloride in the pathophysiology of HF and is now a target of treatment to decrease mortality. The prognostic value of serum chloride in HF has been the subject of much attention. Mechanistically, the macula densa, a region in the renal juxtaglomerular apparatus, relies on chloride levels to sense salt and volume status. The recent discovery of with-no-lysine (K) (WNK) protein kinase as an intracellular chloride sensor sheds light on the possible reason of diuretic resistance in HF. The action of chloride on WNKs results in the upregulation of the sodium-potassium-chloride cotransporter and sodium-chloride cotransporter receptors, which could lead to increased electrolyte and fluid reabsorption. Genetic studies have revealed that a variant of a voltage-sensitive chloride channel (CLCNKA) gene leads to almost a 50% decrease in current amplitude and function of the renal chloride channel. This variant increases the risk of HF. Several trials exploring the prognostic value of chloride in both acute and chronic HF have shown mostly positive results, some even suggesting a stronger role than sodium. However, so far, interventional trials exploring serum chloride as a therapeutic target have been largely inconclusive. This study is a review of the pathophysiologic effects of hypochloremia in HF, the genetics of chloride channels, and clinical trials that are underway to investigate novel approaches to HF management.

Role of endogenous atrial natriuretic peptide on systemic and renal hemodynamics in heart failure rats

1994 ◽  
Vol 267 (1) ◽  
pp. H182-H186 ◽  
Author(s):  
T. Nishikimi ◽  
K. Miura ◽  
N. Minamino ◽  
K. Takeuchi ◽  
T. Takeda
Keyword(s):  
Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Diastolic Pressure ◽  
Urinary Sodium Excretion ◽  
Left Ventricular ◽  
Renal Hemodynamics ◽  
Renal Tubular ◽  
Atrial Natriuretic

To investigate the role of endogenous atrial natriuretic peptide (ANP) in rats with heart failure (HF), we administered HS-142-1 (HS; 3 mg/kg body wt iv), a novel nonpeptide ANP-receptor antagonist, to rats with surgically induced myocardial infarction and sham-operated rats. HF was characterized by a higher left ventricular end-diastolic pressure and higher plasma ANP concentration vs. controls. HS administration significantly reduced the plasma and urinary levels of guanosine 3',5'-cyclic monophosphate in rats with HF [plasma concentration 10.6 +/- 2.6 vs. 2.7 +/- 0.4 nM (P < 0.05); urinary excretion 48 +/- 8 vs. 12 +/- 2 pmol/min (P < 0.05)]. Systemic and renal hemodynamics were unaffected by HS administration. Urine flow (-35%) and urinary sodium excretion (-50%) were significantly decreased after HS only in those rats with HF that had no changes in systemic and renal hemodynamics. These results suggest that the elevated ANP levels in HF do not contribute directly to the maintenance of systemic hemodynamics but rather compensate for the HF mainly via diuresis and natriuresis, achieved by the inhibition of renal tubular reabsorption rather than by renal vasodilatation.

scholarly journals The Role of Ultrafiltration in Patients with Decompensated Heart Failure

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Sandeep A. Kamath
Keyword(s):  
Heart Failure ◽  
Decompensated Heart Failure ◽  
Cardiorenal Syndrome ◽  
Loop Diuretics ◽  
Inpatient Setting ◽  
Effective Volume ◽  
Primary Driver ◽  
High Doses

Congestion, due in large part to hypervolemia, is the primary driver of heart failure (HF) admissions. Relief of congestion has been traditionally achieved through the use of loop diuretics, but there is increasing concern that these agents, particularly at high doses, may be deleterious in the inpatient setting. In addition, patients with HF and the cardiorenal syndrome (CRS) have diminished response to loop diuretics, making these agents less effective at relieving congestion. Ultrafiltration, a mechanical volume removal strategy, has demonstrated promise in achieving safe and effective volume removal in patients with cardiorenal syndrome and diuretic refractoriness. This paper outlines the rationale for ultrafiltration in CRS and the available evidence regarding its use in patients with HF. At present, the utility of ultrafiltration is restricted to selected populations, but a greater understanding of how this technology impacts HF and CRS may expand its use.

scholarly journals Mechanism and management of diuretic resistance in congestive heart failure

2012 ◽  
Vol 17 (1) ◽  
pp. 44-46
Author(s):  
Dipankar Chandra Nag ◽  
AKM Murshed ◽  
Rajashis Chakrabortty ◽  
Md Raziur Rahman
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Sodium Intake ◽  
Diuretic Therapy ◽  
Compensatory Hypertrophy ◽  
Loop Diuretics ◽  
Thick Ascending Limb ◽  
Diuretic Resistance ◽  
First Line Therapy ◽  
Advanced Stages

Diuretic drugs are used almost universally in patients with congestive heart failure, most frequently the potent loop diuretics. Despite their unproven effect on survival, their indisputable efficacy in relieving congestive symptoms makes them first line therapy for most patients. In the treatment of more advanced stages of heart failure diuretics may fail to control salt and water retention despite the use of appropriate doses. Diuretic resistance may be caused by decreased renal function and reduced and delayed peak concentrations of loop diuretics in the tubular fluid, but it can also be observed in the absence of these pharmacokinetic abnormalities. When the effect of a short acting diuretic has worn off, postdiuretic salt retention will occur during the rest of the day. Chronic treatment with a loop diuretic results in compensatory hypertrophy of epithelial cells downstream from the thick ascending limb and consequently its diuretic effect will be blunted. Strategies to overcome diuretic resistance include restriction of sodium intake, changes in dose, changes in timing, and combination diuretic therapy. DOI: http://dx.doi.org/10.3329/jdnmch.v17i1.12193 J. Dhaka National Med. Coll. Hos. 2011; 17 (01): 44-46

scholarly journals Potential Role of Natriuretic Response to Furosemide Stress Test During Acute Heart Failure

2021 ◽  
Vol 14 (6) ◽  
Author(s):  
Pedro Caravaca Pérez ◽  
Jorge Nuche ◽  
Laura Morán Fernández ◽  
David Lora ◽  
Zorba Blázquez-Bermejo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Heart Failure ◽  
Potential Role ◽  
Stress Test ◽  
Adverse Outcomes ◽  
Sample Median ◽  
Diuretic Treatment ◽  
Diuretic Response ◽  
Worse Prognosis

Background: Poor natriuresis has been associated with a poorer response to diuretic treatment and worse prognosis in acute heart failure. Recommendations on how and when to measure urinary sodium (UNa) are lacking. We aim to evaluate UNa quantification after a furosemide stress test (FST) capacity to predict appropriate decongestion during acute heart failure hospitalization. Methods: Patients underwent an FST on day-1 of admission, and UNa was measured 2 hours after, dividing patients into low or high UNa based on the sample median value. A semiquantitative composite congestive score (CCS; 0–9) and NT pro-BNP (N-terminal pro-B-type natriuretic peptide) quantification were assessed before the FST and at day 5 after the FST. Results: Median UNa after FST in the 65 patients included was 113 (97–122) mmol/L. At day 5, a lower proportion of patients with a low UNa reached a 30% decrease in NT-proBNP levels (21 [66%] for low UNa versus 31 [94%] for high UNa; P =0.005) and an appropriate grade of decongestion (CCS<3) (20 [62%] for low UNa versus 32 [97%] for high UNa; P <0.001). A UNa>83 mmol/L 2 hours after FST had a 96% sensitivity to predict an NT-proBNP reduction ≥30% and 95% to predict a CCS<3 at day 5. Low UNa patients presented a lower cumulative diuresis and weight loss and presented more often with prolonged hospitalization, worsening heart failure, and readmission because of acute heart failure or death at 6 months. Conclusions: Low natriuresis after an FST identified patients at a higher risk of an inadequate diuretic response and an inappropriate decongestion. FST-guided diuretic treatment might help to improve decongestion, shorten hospitalizations, and to reduce adverse outcomes.

scholarly journals Long Noncoding RNA SOX2-OT Exacerbates Hypoxia-Induced Cardiomyocytes Injury by Regulating miR-27a-3p/TGFβR1 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Guang Yang ◽  
Chunsheng Lin
Keyword(s):  
Heart Failure ◽  
Cell Apoptosis ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Heart Diseases ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cellular Processes ◽  
Wide Range

Background. Myocardial infarction (MI) was a severe cardiovascular disease resulted from acute, persistent hypoxia, or ischemia condition. Additionally, MI generally led to heart failure, even sudden death. A multitude of research studies proposed that long noncoding RNAs (lncRNAs) frequently participated in the regulation of heart diseases. The specific function and molecular mechanism of SOX2-OT in MI remained unclear. Aim of the Study. The current research was aimed to explore the role of SOX2-OT in MI. Methods. Bioinformatics analysis (DIANA tools and Targetscan) and a wide range of experiments (CCK-8, flow cytometry, RT-qPCR, luciferase reporter, RIP, caspase-3 activity, trans-well, and western blot assays) were adopted to investigate the function and mechanism of SOX2-OT. Results. We discovered that hypoxia treatment decreased cell viability but increased cell apoptosis. Besides, lncRNA SOX2-OT expression was upregulated in hypoxic HCMs. Hereafter, we confirmed that SOX2-OT could negatively regulate miR-27a-3p levels by directly binding with miR-27a-3p, and miR-27a-3p also could negatively regulate SOX2-OT levels. Furthermore, knockdown of SOX2-OT promoted cell proliferation, migration, and invasion, but limited cell apoptosis. However, these effects were reversed by anti-miR-27a-5p. Besides, we verified that miR-27a-3p binding with the 3′UTR of TGFBR1 and SOX2-OT regulated TGFβR1 level by collaborating with miR-27a-3p in HCMs. Eventually, rescue assays validated that the influence of SOX2-OT silence or miR-27a-3p overexpression on cellular processes in cardiomyocytes injury was counteracted by TGFBR1 overexpression. Conclusions. Long noncoding RNA SOX2-OT exacerbated hypoxia-induced cardiomyocytes injury by regulating miR-27a-3p/TGFβR1 axis, which may provide a novel insight for heart failure treatment.

Cardiorenal Syndrome and the Role of Ultrafiltration in Heart Failure

2013 ◽  
Vol 10 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Jason Prosek ◽  
Anil Agarwal ◽  
Samir V. Parikh
Keyword(s):  
Heart Failure ◽  
Cardiorenal Syndrome

scholarly journals Role of liver stiffness in prediction of adverse outcomes in heart failure

2019 ◽  
Vol 73 (2) ◽  
pp. 185-186
Author(s):  
Dhrubajyoti Bandyopadhyay ◽  
Kumar Ashish ◽  
Kartik Dhaduk ◽  
Upasana Banerjee ◽  
Samhati Mondal ◽  
...  
Keyword(s):  
Heart Failure ◽  
Liver Stiffness ◽  
Adverse Outcomes

scholarly journals The Role of Congestion in Cardiorenal Syndrome Type 2: New Pathophysiological Insights into an Experimental Model of Heart Failure

2015 ◽  
Vol 6 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Annalisa Angelini ◽  
Chiara Castellani ◽  
Grazia Maria Virzì ◽  
Marny Fedrigo ◽  
Gaetano Thiene ◽  
...  
Keyword(s):  
Heart Failure ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Heart Tissue ◽  
Heart Cell ◽  
Tubular Damage ◽  
Syndrome Type ◽  
Neutrophil Gelatinase Associated Lipocalin

Background: In cardiorenal syndrome type 2 (CRS2), the role of systemic congestion in heart failure (HF) is still obscure. We studied a model of CRS2 [monocrotaline (MCT)-treated rats] secondary to pulmonary hypertension and right ventricular (RV) failure in order to evaluate the contribution of prevalent congestion to the development of kidney injury. Methods: Ten animals were treated with MCT for 4 weeks until they developed HF. Eleven animals were taken as controls. Signs of hypertrophy and dilatation of the right ventricle demonstrated the occurrence of HF. Brain natriuretic peptide (BNP), serum creatinine (sCreatinine), both kidney and heart neutrophil gelatinase-associated lipocalin (NGAL), matrix metallopeptidase 9 (MMP9), serum cytokines as well as kidney and heart cell death, as assessed by TUNEL, were studied. Results: Rats with HF showed higher BNP levels [chronic HF (CHF) 4.8 ± 0.5 ng/ml; controls 1.5 ± 0.2 ng/ml; p < 0.0001], marked RV hypertrophy and dilatation (RV mass/RV volume: CHF 1.46 ± 0.31, controls 2.41 ± 0.81; p < 0.01) as well as pleural and peritoneal effusions. A significant increase in proinflammatory cytokines and sCreatinine was observed (CHF 3.06 ± 1.3 pg/ml vs. controls 0.54 ± 0.23 pg/ml; p = 0.04). Serum (CHF 562.7 ± 93.34 ng/ml vs. controls 245.3 ± 58.19 ng/ml; p = 0.02) as well as renal and heart tissue NGAL levels [CHF 70,680 ± 4,337 arbitrary units (AU) vs. controls 32,120 ± 4,961 AU; p = 0.001] rose significantly, and they were found to be complexed with MMP9 in CHF rats. A higher number of kidney TUNEL-positive tubular cells was also detected (CHF 114.01 ± 45.93 vs. controls 16.36 ± 11.60 cells/mm2; p = 0.0004). Conclusion: In this model of CHF with prevalent congestion, kidney injury is characterized by tubular damage and systemic inflammation. The upregulated NGAL complexed with MMP9 perpetuates the vicious circle of kidney/heart damage by enhancing the enzymatic activity of MMP9 with extracellular matrix degradation, worsening heart remodeling.

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