How does kidney failure effect drug metabolism?
Although the kidney is largely thought to be responsible for drug elimination, the kidney plays an important role in drug metabolism, thus contributing to need for dose adjustments.
Current drug dosing guidelines are based on CKD, but both CKD and acute kidney injury (AKI) have been associated with decreased metabolism, specifically via cytochrome P450 (CYP) enzymes.
The proposed mechanism is through increased circulating levels of urea, PTH, and cytokines, all of which are thought to downregulate both hepatic and intestinal CYP activity. In addition, individuals in kidney failure have been noted to have decreased drug transport (organic anion transporters and P-glycoprotein) capacity, further decreasing metabolism.
Although the exact mechanism is not fully understood, improvement in drug metabolism has been noted in patients on dialysis.
