2001 T-2000 KW seems to lose it's prime when it drops below 1/4 tank. Real PITA.....anybody know why this happens?

I have to say change fuel filter or filters right off the bat. This new ULSD will clog filters more quickly then the old fuel. You might have already did that, but you didn't say. When the fuel is lower in the tank it has to pull more. With a slightly cloged filter, this would not help.

If it has top draw tanks, it could be a cracked pick up tube. Had this happen to a couple Pete' I have owned/ driven. The tube screws in the top of the tank and the fuel supply hose is screwed into that.

Also, Cat primer pumps( the hand pump) go bad with age and will allow air in the system, causing the same effect, but usually it wouldn't matter what the fuel level in the tank is.

Make sure the primary fuel filter is tightened enough.

We had an International (C12 Cat engine) in the shop with the symptoms you describe.

Checked it over and the primary fuel filter was loose.

Tightened it and that was the end of the problem.

The primary fuel filter is on the suction side of the system, and if it's loose, air will be sucked into the system (instead of fuel).