I have a P250-22 that I got a couple years ago. I liked the modular feature where I could upgrade to different calibers but the 250 was discontinued and the various exchange kits are hard to find. I saw a kit that is a .45. Does anyone know if the frame on the .22 can accommodate that caliber?

While doing a little research. I found this
“Product Description

What's in the Box

P250-22 Compact 22LR DAO Rimfire Pistol
(2) Magazines
Cable Lock
Owner's Manual
Built on the same platform as the centerfire P250 variants, the P250-22 is a rimfire pistol with the unique capability to be converted to fire centerfire rounds. The P250-22 offers an affordable option for target shooters, instructors, and those new to shooting sports. Chambered in the venerable .22LR cartridge, the P250-22 is a reliable, fun-to-shoot handgun for all levels of shooters.”

So it appears yes the exchange kit should work.

It appears your model you have is a compact size.
So it appears that a exchange kit for compact, or carry model should work.

The FCU (fire control unit) from any P250 will work with any P250 Exchange Kit.

I will add that the grip modules for the 45 are different.