It seems like Xerath was some guy who regretted doing what he had done but when Renekton decided to lock himself up with Xerath(don't see why Xerath didn't agree to being locked up) he came out infuriated and mad and wants to kill Nasus.
I mean I thought Xerath was some mad mage guy which is why Renekton became infuriated until we heard Xerath regretted and said he's sorry to Azir upon killing him but now I'm clueless.
Lore team help?
Dud only knows one joke. Anivia would have been researching ways to stay dead after about one month.
"Knock, knock!"
"No."
"C'moooon, it's not like you are doing anything else."
"..."
"You know you want toooo"
"Fine. Who's th-"
"NOT NASUS! AHAHAHAHAHAHAHAHAHAHA!"
Dude spent like a thousand years locked in a tiny room. Something probably just snapped in him. And Xerath was regretful at the time, but again, a thousand years in a tiny room probably altered his state of mind a little bit. He certainly doesn't sound it now in his VO and such.
Admittedly I think the whole Renekton going crazy thing is mostly just a holdover from his previous story.
Hey, hey Renekton.
What?
Hey Renekton. Hey. Renekton? Hey. Hey, Renekton.
WHAT?
Reeeeeeeeeeeeeeeeeeeeenekton. Hey. Hey, Renekton. Hey. Hey there, Hey. He-
WHAT!?!?!
Lightning bolt.
He had to spend a thousand years listening to Xerath sing THIS IS THE SONG THAT NEVER ENDS~
Too many knock-knock jokes.
Yeah I fully agree with LordHippoman,being locked up in a small room for such a long time is probably not good for the mental health.
Also while Xerath did regret setting up Azir,we don't know much about his motives. Xerath might have had other motives besides "becoming free" and he might have seen it as pointless to let all this power go to waste(since he couldn't stop the ritual anyway)
Renekton went mad due to isolation, kinda like Veigar except to an extreme, which is actually why I prefer the reworked lore. He's a lot more sympathetic since he was a good guy up until he went mad and makes Nasus' plight of killing his own brother even more tragic.
Renekton wasn't a bad apple, a traitor, he didn't even try to gain more power. He's a victim of delusions brought on by thousands of years alone with his thoughts. And now Nasus has to put him down.
Although, I kinda prefer some of the other explanations here XD
Thousand years trapped like that. I DON'T want to think more about that. if went from being a good guy to a bloodthirsty psycho. Who know what happened.
You ever hear what happens to people locked in dark holes for a couple of days? Multiply that by, like a couple centuries.
When their lores were still lores,I think it read something like: Nasus Lore: Renekton chose to be locked in with xerath to prevent any escape Renekton Lore: Nasus trapped him inside with Xerath out of fear or so.
Reading this thread, I couldn't help but think... Sure, being locked up in a room like that would be bad for your mental health. However, why would he want to kill Nasus so badly (besides Nasus locking him up in that room, of course!)? I think the answer is Xerath, but not from Xerath playing with him/taunting for millennium, but from Xerath persuading him in such a way. In fact, I almost feel like writing a short story about this... lemme get back to you!
Think of it this way, imagine you're trapped in a room with an unkillable entity of pure energy who's only source of amusement is verbally tormenting you 24/7 for ONE THOUSAND YEARS. Ren can't kill Xerath because Xerath is immortal, and Xerath won't kill Ren because he's just too much fun
Basically 
Nasus is Renekton's brother (I know, ironic, a dog and a crocodile are brothers) and NASUS WAS THE ONE WHO LOCKED XERATH AND RENEKTON IN DIS BOX... under 
Azir's orders :3
The isolation may have been the culprit, however given the state of 'ascension', I'm not sure if time passes the same way for their minds as it does our own.
A thousand years could be sanity destroying, or a blink of an eye. Considering how relatively stable Nasus, Azir, and Xerath are, I suspect there's a different cause (if at all) to Renekton spring boarding off the deep end.
