I’ve got an X-keys, and it works fine. It basically just uses regular keycommands, but with the benefit of sticking your own labels on keys and having it all neatly together. I love the keys, they are very tactile and even though I also have a Euphonix MC Control on which I use the touch screen a lot, the X-keys is better for repeated actions as you get the key response from a normal keyboard.
Downsides? Nuendo isn’t great with alt-shift combinations and you might have to program in a teeny delay on the x-keys unit when keys are executed, otherwise Nuendo might miss the fact that a shift or control key was pressed with a regular key.