One possible plotline could be that Naruto is somehow tricked into leaving with Kisami and Itachi. Maybe they convince him that there is a greater threat that only they can help him face. Along the way, Naruto might start to learn more about their motives and the secrets of their pasts. He could also be in a position where he has to use his own skills and values to influence them.
In this fanfiction, it could be that Naruto is forced to leave with Kisami and Itachi due to a political situation in the ninja world. The three of them then become fugitives. As they run, they form an unlikely bond. Naruto might discover that Kisami and Itachi have some redeeming qualities despite their previous actions. They could end up working together to expose a conspiracy within the ninja villages.
One possible plotline could be that Naruto discovers some long - lost secret about his mother Kushina and decides to leave the village with her to explore this mystery further. Maybe they are on a quest to find some hidden power or knowledge that is related to Kushina's Uzumaki heritage.
One possible plotline could be that Naruto leaves with Tsunade on a mission to find a rare herb that is said to have the power to heal any wound. Along the way, they face various enemies who also want the herb for their own malicious purposes. Naruto's skills and Tsunade's wisdom would be put to the test as they battle their way through.
One possible plotline could be that Naruto is forced into a situation where he has to kill Itachi to protect the Hidden Leaf. Maybe Itachi is being controlled by some dark force and Naruto, with great reluctance, has to end his life to save the village and his friends.
One possible plotline could be that Naruto has his own mission or purpose that is in conflict with Rias's plans or the world she is a part of. So, he decides to leave to pursue his own goals. For example, he might need to go back to the Hidden Leaf to protect it from a new threat that only he can handle. Another could be that Naruto discovers some dark secret about Rias or her group and can't stay with them any longer. He values his own moral code too much to be associated with something he deems wrong.
One possible plotline could be that they become closer friends early on. Since they are the same age, they might train together more often. They could also share secrets that in the original story they wouldn't due to the age gap. For example, they might both have dreams about the future of the village that they can discuss on an equal level.
One possible plotline could be that they got married to form an alliance between two powerful factions secretly. Another could be that they fell in love while on a secret mission together that no one else knew about. Maybe Itachi was on a mission to protect Naruto from afar and they developed feelings over time.
One possible plotline could be that Itachi sees Naruto's potential even at a young age. He might start teaching Naruto basic ninja skills like stealth. For example, Itachi could show Naruto how to move quietly in the forest without making a sound. This early training could give Naruto an edge when he later enters the academy, as he would already have a foundation in some ninja arts.
Perhaps Itachi is being hunted by rogue elements of his own clan who don't agree with his past actions, and Naruto gets caught up in it while trying to protect Itachi. Naruto, being the protagonist, would see the good in Itachi and believe that he doesn't deserve to be killed. So they run away together, and during their journey, Itachi starts to train Naruto in some of the more advanced and secret Uchiha techniques, which in turn helps Naruto become even stronger.
One possible plotline could be that Itachi and Shisui, being the skilled Uchiha they are, take Sakura under their wing to train her in some unique jutsu. Maybe they see her potential and want to help her reach a new level of power. For example, Shisui could teach her his body - flicker technique while Itachi imparts some of his knowledge about genjutsu. This would create an interesting dynamic as Sakura tries to adapt to their different teaching styles.
One possible plotline could be that Sakura discovers a new type of lemonade that has some sort of magical property. Itachi, being a powerful and mysterious figure, is interested in this lemonade for some reason related to his own goals or the well - being of his clan. Sakura, initially hesitant, decides to team up with Itachi to explore the secrets of the lemonade further. Maybe they find out that the lemonade can heal certain dark chakra - related ailments that are plaguing Itachi's clan.