Thread by @AvrahamCooperMD

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There seems to be an association between the use of "normal" saline and acute kidney injury (when compared with other IV fluids).

Why would that be?

#medthread #medtwitter #tweetorial

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We need to first understand 2 things:

💥What is the difference between saline and other "balanced" crystalloid IV fluids?
💥What is the evidence that saline is associated with kidney injury?

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💥How is saline different from other "balanced" crystalloid IV fluids?

💡Saline has⬆️levels of Na/Cl
💡Bc of this difference in composition, when used in large volumes saline⬆️serum Cl levels and causes a hyperchloremic metabolic acidosis

bit.ly/358PJah

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💥What is the evidence that saline is associated with renal injury?

There are several studies suggesting this association. Here's one 👇

bit.ly/2ZG8wbZ

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Because there is significantly more chloride in saline than other IV fluids, let's zoom in and see how that might affect the kidney 👇

Infusing high chloride-containing fluids into dogs decreased renal perfusion and glomerular filtration rate (GFR).

bit.ly/36ei7cy

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💥Why would high serum chloride levels decrease renal blood flow and GFR?

The answer involves the macula densa.

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To review:

💡Macula densa cells sense Na/Cl levels in the distal convoluted tubule (DCT)
💡In response to increased Na/Cl levels in the DCT the macula densa decreases renal blood flow and GFR by inducing renal afferent arteriole vasoconstriction

bit.ly/2Qdwzf7

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Look how close the macula densa and renal afferent arteriole are to each other 👇

ncbi.nlm.nih.gov/pmc/articles/P…

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When exposed to high levels of Cl (and Na) the macula densa cells literally swell.

ncbi.nlm.nih.gov/pubmed/12060602

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Along with swelling the macula densa cells release ATP, signalling nearby afferent arterioles to constrict,⬇️renal blood flow and GFR.

This process is called tubuloglomerular feedback, allowing the kidney to regulate its own perfusion

bit.ly/2ZGbzRs

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ATP release from the macula densa cells is actually stimulated directly by Cl 👇

ncbi.nlm.nih.gov/pmc/articles/P…

So,⬆️Cl sensed by the macula dense leads to⬆️ATP release, which signals afferent renal arterioles to constrict, which⬇️GFR

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Let's summarize:

💡"Normal" saline has⬆️levels of Cl compared w/ other IV crystalloid fluids
💡Increased serum Cl levels⬇️renal blood flow and GFR
💡This occurs because of ATP release from macula densa cells, which causes renal afferent arteriolar vasoconstriction