Sunday, March 14, 2021

Topic Discussion: Chloride in Cardio-Renal Syndrome



At recent ASN Kidney Week 2020, Dr. Amir Kazory really gave a great lecture highlighting the importance of an important ion that often is ignored in CHF and Cardio-renal syndrome.

We should perhaps move away from the Na centric view of CHF.

Some interesting points made in his talk and overall what we know.

1. Hyponatremia is a predictor of CHF outcomes. But when we correct the Na, mortality doesn't improve. - classic V2R antagonist EVEREST trial showed no benefit

2. When we give 3% saline as shown by the Yale group recently in JACC, there is significant weight loss in diuretic resistant patients. 

3. The Na restriction in diet has limited evidence that it works


Some interesting data on Cl in CHF.

One of the first studies done looking at Cl in CHF found that for every 4.1meq/L of drop in Cl, there is 25-30% increase in 5 year-mortality. 


Contemporary advanced CHF cohort suggest that serum chloride levels at admission are independently and inversely associated with mortality in this one study. The prognostic value of serum sodium in CHF was diminished compared with chloride.



Why does this matter? 
Two physiological reasons:

1. Low Chloride can stimulate renin release in macula densa

2. Low intracellular chloride can increase TAL NKCC activity and DCT NCC activity




Interestingly, low chloride patients are also diuretic resistant. 

It would be fascinating to see if increasing Cl, without Na really has a good effect on diuresis. Azetazolamide trials are ongoing as a potential way to do this. Could SLGT2i be potentially working via this mechanism? It is very possible that Cl is a more important player than Na in CHF and Cardio-renal syndrome. Fascinating!!

Check out this excellent review. ( also for figure source)





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