Hepatocellular response to acute kidney injury in the critically ill: serum induces CYP2D6 transcription

Introduction Cytochrome P450 2D6 (CYP2D6) is a clinically important CYP, metabolising approximately 25% common drugs. We investigated the clinical effect of acute kidney injury (AKI) on hepatic CYP2D6 metabolism in critically ill adults, using the probe drug tramadol (abstract 470). We found no effect of AKI but a strong CYP2D6 genotype/phenotype influence on tramadol metabolism. Rodent studies indicate no change or impaired CYP2D6 metabolism in chronic kidney disease and AKI (Refs [1-3]). No published human or animal data has examined CYP2D6 transcription, translation or activity in AKI. Previously we demonstrated no change in CYP2D6 transcription when pooled serum from patients with end-stage kidney disease (ESKD) was applied to human HepG2 cells, known to express the functional CYP2D6*1 allele.