The dynamic relationship between serum chloride and cardiorenal syndrome

Kazory, Amir; Costanzo, María Rosa

doi:10.31083/j.rcm.2020.01.6

Cited by 13 publications

(8 citation statements)

References 37 publications

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“…As previously mentioned, the clinical relevance of chloride in the setting of acute and chronic heart failure has been increasingly recognized. A series of clinical studies have shown that hypochloremia is an independent risk factor for adverse outcomes, and the prognostic significance of serum sodium level, once considered the key cardiorenal connector, might not be as strong as that of chloride [33][34][35][36]. It is within this context that chloride has emerged as a therapeutic target, and investigators have tried to explore the clinical consequences of raising serum chloride levels, whether through sodium-free chloride supplementation or through administration of CA inhibitors.…”

Section: Carbonic Anhydrase Inhibitorsmentioning

confidence: 99%

Cardiorenal Interactions in Acute Heart Failure; Renal Proximal Tubules in the Spotlight

Kazory,

Ronco,

Koratala

2024

Cardiorenal Med

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Background: The maladaptive neurohormonal activation, an integral mechanism in the pathophysiology of heart failure (HF) and cardiorenal syndrome, has a profound impact on renal sodium handling. Congestion is the primary reason for hospitalization of patients with HF and the main target of therapy. As sodium is the main determinant of extracellular volume, the goal is to enhance urinary sodium excretion in order to address excess fluid. The interventions to increase natriuresis have conventionally been focused on distal nephron as the primary segment that counterbalances the effects of loop diuretics. Summary: Recent developments in the field of cardiorenal medicine have resulted in a shift of attention to renal proximal tubules (e.g., emerging evidence on proximal tubular dysfunction beyond handling of sodium). Herein, we discuss the three main mechanisms of sodium transport in the proximal tubules with emphasis on their intrinsic links to one another as well as to more distal transporters of sodium. Then, we provide an overview of the findings of the most recent clinical studies that have tried to enhance the conventional decongestive strategies through simultaneous blockade of these mechanisms. Key Message: Interventions aiming at renal proximal tubules have the potential to significantly improve our ability to decongest patients with acute HF.

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Section: Carbonic Anhydrase Inhibitorsmentioning

confidence: 99%

Cardiorenal Interactions in Acute Heart Failure; Renal Proximal Tubules in the Spotlight

Kazory,

Ronco,

Koratala

2024

Cardiorenal Med

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“…The choice of the second diuretic agent may be determined by several factors such as its site of action, the potential side effects, and the evidence from contemporary trials supporting their benefit. 14,15…”

Section: Diuretics and Natriuresismentioning

confidence: 99%

“…[36][37][38] Maladaptive neurohormonal activation and diuretic resistance have been proposed as potential mechanisms to explain this phenomenon. 15,39 These observations have generated interest in an old class of diuretics, the carbonic anhydrase (CA) inhibitors, that can increase serum chloride levels. 40 In the proximal tubules, the hydrogen secreted into the lumen combines with bicarbonate to form carbonic acid, which is rapidly dehydrated to CO 2 and H 2 O by CA.…”

Section: Carbonic Anhydrase Inhibitorsmentioning

confidence: 99%

Combination Diuretic Therapy to Counter Renal Sodium Avidity in Acute Heart Failure

Kazory

2023

CJASN

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In contrast to significant advances in the management of patients with chronic heart failure over the past few years, there has been little change in how patients with acute heart failure are treated. Symptoms and signs of fluid overload are the primary reason for hospitalization of patients who experience acute decompensation of heart failure. Intravenous loop diuretics remain the mainstay of therapy in this patient population, with a significant subset of them showing suboptimal response to these agents leading to incomplete decongestion at the time of discharge. Combination diuretic therapy, that is, using loop diuretics along with an add-on agent, is a widely applied strategy to counter renal sodium avidity through sequential blockade of sodium absorption within renal tubules. The choice of the second diuretic is affected by several factors, including the site of action, the anticipated secondary effects, and the available evidence on their efficacy and safety. While the current guidelines recommend combination diuretic therapy as a viable option to overcome suboptimal response to loop diuretics, it is also acknowledged that this strategy is not supported by strong evidence and remains an area of uncertainty. The recent publication of landmark studies has regenerated the interest in sequential nephron blockade. In this article, we provide an overview of the results of the key studies on combination diuretic therapy in the setting of acute heart failure and discuss their findings primarily with regard to the effect on renal sodium avidity and cardiorenal outcomes.

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“…Their main restriction is to the uid compartment outside the cell [17][18][19]. Chloride in the blood plays a vital role in a variety of physiological functions in the human body, including regulating osmotic pressure, maintaining the electrical balance of bodily uids, facilitating muscle function, and controlling blood pressure [18,20,21]. The kidney and gastrointestinal system are primarily responsible for controlling serum chloride levels.…”

Section: Introductionmentioning

confidence: 99%

Association between serum chloride levels and estimated glomerular filtration rate among US adults: evidence from NHANES 1999 - 2018

Zhao,

Li,

Fei

et al. 2024

Preprint

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Purpose Chloride, the predominant anion in extracellular fluid from humans, is essential to maintaining homeostasis. One important metric for thoroughly assessing kidney function is the estimated glomerular filtration rate (eGFR). However, the relationship between variations in serum chloride concentration and eGFR in general populations has been poorly studied. Therefore, the purpose of this study is to elucidate the correlation between plasma chloride levels and eGFR within the United States’ adult population. Methods This cohort study was conducted using data from the National Health and Nutrition Examination Survey (NHANES), which covered the years 1999 to 2018. We employed multiple linear regression analysis and subgroup analysis to evaluate the correlation between serum chloride concentration and eGFR. To examine the nonlinear association between serum chloride levels and eGFR, restricted cubic spline analyses were employed. Results Data from 49,008 participants in this cohort study were used for the chloride analysis. In the comprehensively adjusted model, a noteworthy inverse relationship was discovered between chloride plasma concentration and eGFR. Restricted cubic spline analyses revealed a significant nonlinear relationship between chloride levels and eGFR (P for overall < 0.001 and P for nonlinear < 0.001). A significant interaction was observed between eGFR and plasma chloride concentration (all P < 0.001 for interaction) among the subgroups characterized by sex, household income to poverty ratio, BMI, hypertension, and diabetes. Conclusion Our findings suggest that higher levels of chloride plasma concentration were linked to decreased eGFR. These findings underscore the significance of monitoring chloride plasma concentration as a potential indicator for identifying individuals at risk of developing chronic kidney disease (CKD).

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The dynamic relationship between serum chloride and cardiorenal syndrome

Cited by 13 publications

References 37 publications

Cardiorenal Interactions in Acute Heart Failure; Renal Proximal Tubules in the Spotlight

Cardiorenal Interactions in Acute Heart Failure; Renal Proximal Tubules in the Spotlight

Combination Diuretic Therapy to Counter Renal Sodium Avidity in Acute Heart Failure

Association between serum chloride levels and estimated glomerular filtration rate among US adults: evidence from NHANES 1999 - 2018

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