The stock 245 tires are "E" load rating. When the time comes to get new tires, I would like to go just one size up (to 265). Will this affect my ability to tow a 12,000 lb fifth wheel?

Nope, 265's would fine. Many tow that much with 265's and larger.

Agree with abear, negligible at 12k lbs. IIRC several have posted an adverse impact upon their mpg's. JJ :)

The hitch only puts so much weight on the truck and that is well within the operating weight of your existing tires... so you might as well run out what came with the truck and save yourself some money NOT buying new tires you dont need. :)

VR

I did this upgrage (keeping the factory 2500HD alloys) because my hitch weight, plus heavy aux fuel tank/cargo box, was getting over the rating of the 245's. So far its gone well, no problems. Haven't noticed any mileage change. They're about 3% more in diameter which gives a slight speedo error & gear ratio change. You need to weigh you rear axle to see if you really need this.