Emma Sing comes in at full-back in Kildunne's place for Saturday's rematch (00:00 BST) against Canada in Ottawa, while Tatyana Heard and Claudia Moloney-MacDonald - backline starters in the defeat - drop out of the matchday squad entirely.
Helena Rowland and Mia Venner replace Heard and Moloney-MacDonald at inside centre and wing respectively.
In the fourth change to the starting line-up, Sadia Kabeya, who appeared off the bench last week on her comeback from a leg injury, starts with Alex Matthews, two-time Rugby World Cup winner, dropping to the bench.
Exeter's Flo Robinson and Sale's Hollie Aitchison are included on the bench as a new-look set of half-back replacements.
Sing, a rangy runner who can also kick goals, started two matches at full-back during England's Six Nations campaign, with Kildunne switching to a different position on the wing on each occasion.
Sing's Gloucester-Hartpury team-mate Venner made her England debut in 2020 aged just 17.
Venner has won only another four caps since but was putting pressure on England's more established back three at the start of this year, appearing in wins over Scotland and Italy.
The 24-year-old finished as the PWR's joint top try-scorer last season, crossing 12 times.
Moloney-MacDonald cost her side an early try in the defeat by Canada when, after doing superbly to pick Jess Breach's pass off her toes, she spilled the ball over the line in the sixth minute.
"We've earned a strong period but nothing about it is owed to us going forward," said Mitchell.
"Friday [Saturday 00:00 BST] is an opportunity to apply sustained pressure, learn from what we missed and come out the other side better than we went in."