Role of kidney chloride channels in health and disease

Veizis, I. Elias; Cotton, Calvin U.

doi:10.1007/s00467-006-0355-4

Cited by 20 publications

(16 citation statements)

References 63 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with this observation, Xie and Shafer [51] demonstrated that the treatment with cAMP stimulates Cl − secretion via cystic fibrosis transmembrane conductance regulator as well as ENaC-mediated Na + absorption in MDCK cells. This could be in agreement with a lack of a kidney phenotype in cystic fibrosis patients [53], [54], in which CFTR activity is compromised, but chloride intracellular concentration could be modulated by the plethora of chloride channels [55] and transporters [56] that are active in kidney cells.…”

Section: Discussionsupporting

confidence: 68%

Hypertension-Linked Mutation of α-Adducin Increases CFTR Surface Expression and Activity in HEK and Cultured Rat Distal Convoluted Tubule Cells

et al. 2012

View full text Add to dashboard Cite

The CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) activity and localization are influenced by the cytoskeleton, in particular by actin and its polymerization state. In this study we investigated whether the expression of the hypertensive mutations of α-adducin (G460W-S586C in humans, F316Y in rats), an actin capping protein, led to a functional modification of CFTR activity and surface expression. The experiments were performed on HEK293 T cells cotransfected with CFTR and the human wild type (WT) or G460W mutated α-adducin. In whole-cell patch-clamp experiments, both the CFTR chloride current and the slope of current activation after forskolin addition were significantly higher in HEK cells overexpressing the G460W adducin. A higher plasma membrane density of active CFTR channels was confirmed by cell-attached patch-clamp experiments, both in HEK cells and in cultured primary DCT cells, isolated from MHS (Milan Hypertensive Strain, a Wistar rat (Rattus norvegicus) hypertensive model carrying the F316Y adducin mutation), compared to MNS (Milan Normotensive Strain) rats. Western blot experiments demonstrated an increase of the plasma membrane CFTR protein expression, with a modification of the channel glycosylation state, in the presence of the mutated adducin. A higher retention of CFTR protein in the plasma membrane was confirmed both by FRAP (Fluorescence Recovery After Photobleaching) and photoactivation experiments. The present data indicate that in HEK cells and in isolated DCT cells the presence of the G460W-S586C hypertensive variant of adducin increases CFTR channel activity, possibly by altering its membrane turnover and inducing a retention of the channel in the plasmamembrane. Since CFTR is known to modulate the activity of many others transport systems, the increased surface expression of the channel could have consequences on the whole network of transport in kidney cells.

show abstract

Section: Discussionsupporting

confidence: 68%

Hypertension-Linked Mutation of α-Adducin Increases CFTR Surface Expression and Activity in HEK and Cultured Rat Distal Convoluted Tubule Cells

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Cl channels are expressed in almost all cells in the body. Dysfunctions in the Cl channel result in a broad spectrum of diseases [2]. …”

Section: Introductionmentioning

confidence: 99%

Chloride alterations in hospitalized patients: Prevalence and outcome significance

2017

View full text Add to dashboard Cite

Serum Cl (sCl) alterations in hospitalized patients have not been comprehensively studied in recent years. The aim of this study is to investigate the prevalence and outcome significance of (1) sCl alterations on hospital admission, and (2) sCl evolution within the first 48 hr of hospital admission. We conducted a retrospective study of all hospital admissions in the years 2011–2013 at Mayo Clinic Rochester, a 2000-bed tertiary medical center. Outcome measures included hospital mortality, length of hospital stay and discharge disposition. 76,719 unique admissions (≥18 years old) were studied. Based on hospital mortality, sCl in the range of 105–108 mmol/L was found to be optimal. sCl <100 (n = 13,611) and >108 (n = 11,395) mmol/L independently predicted a higher risk of hospital mortality, longer hospital stay and being discharged to a care facility. 13,089 patients (17.1%) had serum anion gap >12 mmol/L; their hospital mortality, when compared to 63,630 patients (82.9%) with anion gap ≤12 mmol/L, was worse. Notably, patients with elevated anion gap displayed a progressively worsening mortality with rising sCl. sCl elevation within 48 hr of admission was associated with a higher proportion of 0.9% saline administration and was an independent predictor for hospital mortality. Moreover, the magnitude of sCl rise was inversely correlated to the days of patient survival. In conclusion, serum Cl alterations on admission predict poor clinical outcomes. Post-admission sCl increase, due to Cl-rich fluid infusion, independently predicts hospital mortality. These results raise a critical question of whether iatrogenic cause of hyperchloremia should be avoided, a question to be addressed by future prospective studies.

show abstract

“…Cellular Cl alterations due to dysfunctions in Cl channels result in a broad spectrum of diseases (Puljak and Kilic, 2006;Veizis and Cotton, 2007;Tang et al, 2010). Thus, conceptually, hyperchloremia caused by saline infusion cannot be viewed as normal.…”

Section: Hyperchloremia and Hyperchloremic Acidosis Are Abnormalmentioning

confidence: 99%

0.9% saline is neither normal nor physiological

Sun

Yap

et al. 2016

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

Abstract:The purpose of this review is to objectively evaluate the biochemical and pathophysiological properties of 0.9% saline (henceforth: saline) and to discuss the impact of saline infusion, specifically on systemic acid-base balance and renal hemodynamics. Studies have shown that electrolyte balance, including effects of saline infusion on serum electrolytes, is often poorly understood among practicing physicians and inappropriate saline prescribing can cause increased morbidity and mortality. Large-volume (>2 L) saline infusion in healthy adults induces hyperchloremia which is associated with metabolic acidosis, hyperkalemia, and negative protein balance. Saline overload (80 ml/kg) in rodents can cause intestinal edema and contractile dysfunction associated with activation of sodium-proton exchanger (NHE) and decrease in myosin light chain phosphorylation. Saline infusion can also adversely affect renal hemodynamics. Microperfusion experiments and real-time imaging studies have demonstrated a reduction in renal perfusion and an expansion in kidney volume, compromising O 2 delivery to the renal parenchyma following saline infusion. Clinically, saline infusion for patients post abdominal and cardiovascular surgery is associated with a greater number of adverse effects including more frequent blood product transfusion and bicarbonate therapy, reduced gastric blood flow, delayed recovery of gut function, impaired cardiac contractility in response to inotropes, prolonged hospital stay, and possibly increased mortality. In critically ill patients, saline infusion, compared to balanced fluid infusions, increases the occurrence of acute kidney injury. In summary, saline is a highly acidic fluid. With the exception of saline infusion for patients with hypochloremic metabolic alkalosis and volume depletion due to vomiting or upper gastrointestinal suction, indiscriminate use, especially for acutely ill patients, may cause unnecessary complications and should be avoided. More education regarding saline-related effects and adequate electrolyte management is needed.

show abstract

Role of kidney chloride channels in health and disease

Cited by 20 publications

References 63 publications

Hypertension-Linked Mutation of α-Adducin Increases CFTR Surface Expression and Activity in HEK and Cultured Rat Distal Convoluted Tubule Cells

Hypertension-Linked Mutation of α-Adducin Increases CFTR Surface Expression and Activity in HEK and Cultured Rat Distal Convoluted Tubule Cells

Chloride alterations in hospitalized patients: Prevalence and outcome significance

0.9% saline is neither normal nor physiological

Contact Info

Product

Resources

About