Thread by @amyaimei

The 🎩baron of kidney stone prevention has been citrate supplementation.

📖Let’s quickly review hypocitraturia and its relationship to stones.

Where is most of your citrate reabsorbed?

Which condition is ❌NOT associated with hypocitraturia?

Before we get into the #tweetorialanswers, let’s establish that hypocitraturia is a risk factor.

Previous data show around 📊46-60% of stone formers have hypocitraturia.

In Ca stone formers, hypocitraturia is the 📊sole abnormality in 10%.

pubmed.ncbi.nlm.nih.gov/32715836/

Citrate prevents 🌟agglomeration, growth, and adhesion of crystals, and thus reducing stone risk.

Specifically, it...
- ⤵️free UrCa
- ⤴️urine pH
- ⤴️uric acid solubility
- ⤴️osteopontin (❌inhibits Ca stones)
- ⤴️inhib effect of Tamm-Horsfall

pubmed.ncbi.nlm.nih.gov/24628885/

Citrate is freely filtered, but 65-90% of the filtered citrate is reabsorbed in the 🌟PT through NaDC-1 cotransporter. #tweetorialanswers

pubmed.ncbi.nlm.nih.gov/19918339/

A key point is that it prefers citrate2- instead of citrate 3-.🔑

🧐This helps explain why acidosis leads to hypocitraturia.

📌 tubular acidosis: ⤴️ 2-/3- ratio so more reabs
📌 systemic acidosis:⤴️ # and activity of NaDC-1
📌 intracell acidosis: ⤴️ #mito metabolism of citrate

Hypokalemia is another risk factor for hypocitraturia thought to be due to resulting intracellular acidosis.

And of course acidosis is also associated with hypercalciuria.

https://twitter.com/amyaimei/status/1336724962497814529

Understanding that 🔑acidosis affect urinary citrate excretion, you can understand how different medications and GI/renal etiologies may result in hypocitraturia.

(Excessive 🌟Vitamin C is associated with hyperoxaluria) #tweetorialanswers

How can we manage hypocitraturia?

📌Dietary changes
- low Na diet🧂
- increase fruit and veggies 🥦🍊
- reduce animal protein intake (high acid load)🍗🥩

Diet changes can ⤴️UrCitr by up to 20-25%📊

📌Citrate therapy
K citrate > Mg citrate > Na citrate

ncbi.nlm.nih.gov/books/NBK56439…

But wait…if I give citrate, won’t I just increase the risk of CaP stones????

Doesn’t look like it. Bu

In an analysis of 259 patients on Kcitrate, the urine pH increased from 5.9 to 6.4.

An increase of urine pH > 7-7.5 could🤔theoretically increase your risk, but ⚖️benefits outweigh this theoretical risk.

pubmed.ncbi.nlm.nih.gov/19152932/
pubmed.ncbi.nlm.nih.gov/22595827/

In summary
📌hypocitraturia increases risk of stones
📌acidosis and hypoK worsen hypocitraturia
📌Rx: low Na, more fruits & veggies, less animal protein, citrate therapy 🧂🥦🍋🍗

Forgot to cite this case report that details how potentially hyperaldosteronism may increase risk of kidney stones through hypercalciuria and hypocitraturia.

pubmed.ncbi.nlm.nih.gov/15211456/