For example, secondary analysis of a prospective, multicenter, Sapphire study enrolling 333 critically ill adult patients receiving vancomycin alone, piperacillin–tazobactam alone, or vancomycin plus piperacillin–tazobactam combination demonstrated that in patients with stages 2–3 AKI, urinary TIMP2-IGFBP7 was significantly elevated at the day of vancomycin initiation, peaking at the following day; while, serum creatinine was significantly elevated and peaked one day after starting the therapy [222]. Here, TIMP2 is linked to acute kidney injury.