Dx Dialogues: transcellular and paracellular transport inhibitors for CKD and hyperphosphatemia

Nephrologist Sean Hashmi, MD, discusses transport inhibitors - the "newer kids on the block" - in the treatment of CKD and hyperphosphatemia.

Transcript

00:00

The newer kids on the block, which we call transport inhibitors, these work specifically by inhibiting the gut wall from taking

00:08

phosphate inside them. Now, there's two specific pathways.

00:14

The first one is what we call the paracellular pathway or next to cells. And the other one is the transcellular pathway,

00:21

which is going to be through the cells. So when we talk about the first one, which is drugs names such as tenapanor,

00:27

these are NH3 inhibitors. And essentially, what they're doing is they're blocking the pathway in between cells.

00:35

And remember, this pathway is going to end up accounting for about 65% to 80% of the absorption.

00:42

Then we get into the transcellular pathway. Now, this is specifically referring to NaPi2b.

00:48

Now, when we talk about NaPi2b blocking the transcellular pathway, we're looking at essentially getting closer

00:56

to about 20% of absorption that's going to end up going in. One of the things that becomes very important to understand

01:02

is with chronic phosphate binder use, you actually upregulate the NaPi2b.

01:09

The gut is essentially building up more doors to allow for more absorption occurring. And this is why you'll end up seeing some of your patients

01:17

plateauing, despite the fact that you continue to increase phosphate binder dosages.

01:23

And so these transporter inhibitors, they're going to be able to address this compensation directly. [AUDIO LOGO]