This discussion may contain spoilers!
Really have no idea, he seems too major to just disappear like that for good. But it seems weird with what was said; why would Luke just leave because Kenny told him to get lost. With the walkers everywhere and such.
Part of me feels Kenny attacked or even killed Luke as he wanted to keep Clementine. Maybe extreme but its a possibility.
Also slightly off topic but he could still be Rebecca's baby daddy as when she insists on searching for him and Alvin back at the lodge she says "Dammit Luke" Not Dammit Alvin.
I'm sure Luke will be back next episode but his disappearance is still a puzzle.