Relationships of hyperchloremia with hypertension and proteinuria in patients with chronic kidney disease

Takahashi, Akira; Maeda, Kazuya; Sasaki, Kensuke; Doi, Shigehiro; Nakashima, Ayumu; Doi, Toshiki; Takao, Masaki

doi:10.1007/s10157-022-02229-6

Cited by 5 publications

(5 citation statements)

References 25 publications

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“…In addition, it has been reported that there was a positive association between hyperchloremia and in-hospital mortality in hospitalized patients [ 110 ]. Moreover, in a recent study in patients with chronic kidney disease, hyperchloremia was an independent predictor of hypertension and proteinuria [ 111 ]. Taking these observational studies together, it might be possible to speculate that hyperchloremia might lead to blood pressure elevation and hence to poor prognosis.…”

Section: Clinical Perspectivesmentioning

confidence: 99%

Chloride Ions, Vascular Function and Hypertension

Gotō

Kitazono

2022

Biomedicines

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Blood pressure is determined by cardiac output and systemic vascular resistance, and mediators that induce vasoconstriction will increase systemic vascular resistance and thus elevate blood pressure. While peripheral vascular resistance reflects a complex interaction of multiple factors, vascular ion channels and transporters play important roles in the regulation of vascular tone by modulating the membrane potential of vascular cells. In vascular smooth muscle cells, chloride ions (Cl−) are a type of anions accumulated by anion exchangers and the anion–proton cotransporter system, and efflux of Cl− through Cl− channels depolarizes the membrane and thereby triggers vasoconstriction. Among these Cl− regulatory pathways, emerging evidence suggests that upregulation of the Ca2+-activated Cl− channel TMEM16A in the vasculature contributes to the increased vascular contractility and elevated blood pressure in hypertension. A robust accumulation of intracellular Cl− in vascular smooth muscle cells through the increased activity of Na+–K+–2Cl− cotransporter 1 (NKCC1) during hypertension has also been reported. Thus, the enhanced activity of both TMEM16A and NKCC1 could act additively and sequentially to increase vascular contractility and hence blood pressure in hypertension. In this review, we discuss recent findings regarding the role of Cl− in the regulation of vascular tone and arterial blood pressure and its association with hypertension, with a particular focus on TMEM16A and NKCC1.

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Section: Clinical Perspectivesmentioning

confidence: 99%

Chloride Ions, Vascular Function and Hypertension

Gotō

Kitazono

2022

Biomedicines

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“…Serum chlorine has a distinct role in humoral homeostasis, affecting the heart, kidney, and neurohormonal system 38 . Hyperchloremia promotes the development of hypertension and proteinuria in chronic kidney disease 39 . In addition, hospital‐acquired hyperchloremia (but not hypochloremia) has been linked to an increased in‐hospital mortality 40 .…”

Section: Discussionmentioning

confidence: 99%

“… 38 Hyperchloremia promotes the development of hypertension and proteinuria in chronic kidney disease. 39 In addition, hospital‐acquired hyperchloremia (but not hypochloremia) has been linked to an increased in‐hospital mortality. 40 According to some studies, the myocardial anion transporters can transport chloride, and the negative chloride current or transporter protein is involved in the adaptive remodeling process of cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a nomogram to predict left ventricular hypertrophy in low‐risk patients with hypertension

Zhang,

He,

et al. 2024

J of Clinical Hypertension

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Electrocardiography (ECG) is an accessible diagnostic tool for screening patients with hypertensive left ventricular hypertrophy (LVH). However, its diagnostic sensitivity is low, with a high probability of false‐negatives. Thus, this study aimed to establish a clinically useful nomogram to supplement the assessment of LVH in patients with hypertension and without ECG‐LVH based on Cornell product criteria (low‐risk hypertensive population). A cross‐sectional dataset was used for model construction and divided into development (n = 2906) and verification (n = 1447) datasets. A multivariable logistic regression risk model and nomogram were developed after screening for risk factors. Of the 4353 low‐risk hypertensive patients, 673 (15.4%) had LVH diagnosed by echocardiography (Echo‐LVH). Eleven risk factors were identified: hypertension awareness, duration of hypertension, age, sex, high waist‐hip ratio, education level, tea consumption, hypochloremia, and other ECG‐LVH diagnostic criteria (including Sokolow–Lyon, Sokolow–Lyon products, and Peguero–Lo Presti). For the development and validation datasets, the areas under the curve were 0.724 (sensitivity = 0.606) and 0.700 (sensitivity = 0.663), respectively. After including blood pressure, the areas under the curve were 0.735 (sensitivity = 0.734) and 0.716 (sensitivity = 0.718), respectively. This novel nomogram had a good predictive ability and may be used to assess the Echo‐LVH risk in patients with hypertension and without ECG‐LVH based on Cornell product criteria.

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“…Hypochloraemia ([Cl − ] e < 96 mM) is observed in patients with chronic cardiac failure and is associated with higher risk of mortality in patients with acute or chronic heart failure [ 32 , 33 , 34 , 35 ]. Hyperchloremia ([Cl − ] e > 110 mM), which accompanies a range of kidney disturbances, is an independent predictor for hypertension [ 36 , 37 ], and positively associated with increased mortality rate of hospitalised patients [ 34 ]. These conditions are expected to impact E Cl and thus the magnitude of TMEM16A currents.…”

Section: Chloride Homeostasis In Vascular Cellsmentioning

confidence: 99%

The TMEM16A channel as a potential therapeutic target in vascular disease

Al-Hosni,

Kaye,

Choi

et al. 2024

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review The transmembrane protein 16A (TMEM16A) Ca2+-activated Cl− channel constitutes a key depolarising mechanism in vascular smooth muscle and contractile pericytes, while in endothelial cells the channel is implicated in angiogenesis and in the response to vasoactive stimuli. Here, we offer a critical analysis of recent physiological investigations and consider the potential for targeting TMEM16A channels in vascular disease. Recent findings Genetic deletion or pharmacological inhibition of TMEM16A channels in vascular smooth muscle decreases artery tone and lowers systemic blood pressure in rodent models. Inhibition of TMEM16A channels in cerebral cortical pericytes protects against ischemia-induced tissue damage and improves microvascular blood flow in rodent stroke models. In endothelial cells, the TMEM16A channel plays varied roles including modulation of cell division and control of vessel tone through spread of hyperpolarisation to the smooth muscle cells. Genetic studies implicate TMEM16A channels in human disease including systemic and pulmonary hypertension, stroke and Moyamoya disease. Summary The TMEM16A channel regulates vascular function by controlling artery tone and capillary diameter as well as vessel formation and histology. Preclinical and clinical investigations are highlighting the potential for therapeutic exploitation of the channel in a range of maladaptive states of the (micro)circulation.

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Relationships of hyperchloremia with hypertension and proteinuria in patients with chronic kidney disease

Cited by 5 publications

References 25 publications

Chloride Ions, Vascular Function and Hypertension

Chloride Ions, Vascular Function and Hypertension

Construction and validation of a nomogram to predict left ventricular hypertrophy in low‐risk patients with hypertension

The TMEM16A channel as a potential therapeutic target in vascular disease

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