Endogenous factors involved in the progression of cisplatin nephropathy remain undetermined. Here, we demonstrate the toxico-pathological roles of indoxyl sulfate (IS), a sulfate-conjugated uremic toxin, and sulfotransferase 1A1 (SULT1A1), an enzyme involved in its synthesis, in cisplatin-induced acute kidney injury using -deficient ( KO) mice. With cisplatin administration, severe kidney dysfunction, tissue damage, and apoptosis were attenuated in (KO) mice.