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When was the last time you were paged about a serum Cl- level? Probably never.
Despite being the most abundant anion in the body, Cl- is under appreciated
Here’s why it matters (esp in heart failure!)
#tweetorial #medtwitter #nephtwitter #cardiotwitter #NSMC
Despite being the most abundant anion in the body, Cl- is under appreciated
Here’s why it matters (esp in heart failure!)#tweetorial #medtwitter #nephtwitter #cardiotwitter #NSMC
There is evidence supporting the use of hypertonic saline in patients with decompensated heart failure
See excellent blog post by @aldorodrig
https://www.renalfellow.org/2019/04/03/the-paradox-of-hypertonic-saline-use-in-heart-failure/
Mechanistically it never made sense to me, until I realized I may be focusing on the wrong ion
See excellent blog post by @aldorodrig
https://www.renalfellow.org/2019/04/03/the-paradox-of-hypertonic-saline-use-in-heart-failure/Mechanistically it never made sense to me, until I realized I may be focusing on the wrong ion
Chloride MAY be the 
here. Something that will hopefully be more clear after the completion of ongoing trials
https://clinicaltrials.gov/ct2/show/NCT03446651?term=lysine+chloride&draw=2&rank=2
In heart failure patients
Cl- is associated with
1. Poor Prognosis
2. Neurohumoral activation
3. Diuretic Resistance
here. Something that will hopefully be more clear after the completion of ongoing trials https://clinicaltrials.gov/ct2/show/NCT03446651?term=lysine+chloride&draw=2&rank=2In heart failure patients
Cl- is associated with1. Poor Prognosis
2. Neurohumoral activation
3. Diuretic Resistance
Let's establish that Cl- has prognostic consequences in HF
Cl- associated with
mortality
Assoc. is INDEPENDENT of serum Na levels
Unclear whetherCl- is a therapeutic target or a marker of disease severity, ie sodium levels by 
V2 provides no mortality benefit
Cl- has prognostic consequences in HFCl- associated withmortalityAssoc. is INDEPENDENT of serum Na levelsUnclear whetherCl- is a therapeutic target or a marker of disease severity, ie sodium levels by V2 provides no mortality benefit
Cl- plays a vital role in kidney physiologyThe Macula densa renin release in response to a in CHLORIDE levels via the NKCC2 transporterInfusion of Cl-, either with Na or lysine, PRA, not seen with other sodium salts = renin release is dependent on Cl-
This is important due to the role of neurohumoral activation in heart failure ptsInitially compensatory to maintain organ perfusionBecomes maladaptive over time (hence benefit of RAAS inhibitors)So hypothetically maintaining normochloremia MAY reduce RAAS activation
Low Cl- also plays a role in diuretic resistance
Common problem in HF pts
Loop diuretic resistance is due to DCT hypertrophy
In rat models, loop diuretic infusionthe number of NCC cotransporters
How does this relate to Cl-?
Cl- is assoc. with diuretic efficiency
Common problem in HF ptsLoop diuretic resistance is due to DCT hypertrophyIn rat models, loop diuretic infusionthe number of NCC cotransportersHow does this relate to Cl-?
Cl- is assoc. with diuretic efficiency
What’s the mechanism?
Themay be the WNK kinases, specifically WNK1 and WNK4, which regulate the sodium chloride cotransporter (NCC)
Simplistic view: WNK1 stimulates and WNK4 inhibits NCC activity
Both WNK1 and WNK4 have been shown to be intracellular chloride sensors
The
may be the WNK kinases, specifically WNK1 and WNK4, which regulate the sodium chloride cotransporter (NCC)Simplistic view: WNK1 stimulates and WNK4 inhibits NCC activityBoth WNK1 and WNK4 have been shown to be intracellular chloride sensors
Missense mutations in WNK4=NCC & DCT hyperplasia (as seen w/diuretic resistance!)Cl- insensitive WNK4
develop HTN andNCC activity WNK1 autoactivation is inhibited by Cl- WithCl- WNK1 autophosphorylates and becomes activeSo Cl-=WNK1 & WNK4= NCC
Conclusion:
In heart failure patients Cl- is independently associated with
Poor Prognosis
Neurohumoral Activation
Diuretic Resistance
Yet another reason you should care about chloride
Thanks to @amyaimei for help editing this tweetorial
In heart failure patients Cl- is independently associated with
Poor PrognosisNeurohumoral ActivationDiuretic ResistanceYet another reason you should care about chloride
Thanks to @amyaimei for help editing this tweetorial
