title: Acute kidney injury in patients with inactive cytochrome P450 polymorphisms.
abstract: Medications are a major source of acute kidney injury, especially in critically ill patients. Medication-induced renal injury can occur through a number of mechanisms. We present two cases of acute kidney injury (AKI) where inactive cytochrome P450 (CYP) polymorphism may have played a role. The first patient developed a biopsy-proven allergic interstitial nephritis following urethrotomy. Genetic testing revealed the patient to be heterozygous for an inactivating polymorphism CYP2C9*3 and homozygous for an inactivating polymorphism CYP2D6*4. Patient had received several doses of promethazine, which is metabolized by CYP2D6*4. Another patient developed AKI on several occasions after exposure to lansoprazole and allopurinol. CYP testing revealed the patient to be homozygous for inactivating polymorphism CYP2C19*2, which is responsible for the metabolism of lansoprazole. These are the first two cases of AKI associated with non-functional polymorphisms of cytochrome P450 superfamily. While the exact mechanism has not been worked out, it introduced the possibility of a new source of kidney injury.
authors.affiliation: Mayo Clinic Rochester, Division of Nephrology and Hypertension, Rochester, Minnesota, USA. Leung.nelson@mayo.edu
authors.forename: Nelson
authors.initials: N
authors.lastname: Leung
authors.forename: Alfonso
authors.initials: A
authors.lastname: Eirin
authors.forename: Maria V
authors.initials: MV
authors.lastname: Irazabal
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Maddox
authors.forename: Heidi D
authors.initials: HD
authors.lastname: Gunderson
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.forename: Vesna D
authors.initials: VD
authors.lastname: Garovic
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000009:adverse effects*; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics; D000897:Anti-Ulcer Agents / Q000009:adverse effects*; D000932:Antiemetics / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics; D011110:Polymorphism, Genetic; D011398:Promethazine / Q000009:adverse effects*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D000932:Antiemetics; D064747:Lansoprazole; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D011398:Promethazine