How does renal impairment typically affect clearance of renally eliminated drugs?

• A. Clr increases with reduced CrCl
• B. Clr unchanged with CrCl changes
• C. Clr decreases with reduced CrCl, requiring dose or interval adjustment to maintain Css
• D. Renal impairment has no effect on dosing

Answer: (C)

Renal clearance of drugs that are eliminated by the kidney depends on kidney function. When renal function is reduced, CrCl falls, so the renal clearance (Clr) decreases. With lower clearance, the body removes the drug more slowly, causing the elimination half-life to increase and overall exposure (AUC) at a given dose to rise. To keep the steady-state concentration (Css) at the desired level, you must lower the dose or extend the dosing interval (or do both). In short, renal impairment typically reduces clearance of renally eliminated drugs and requires dose or interval adjustments to maintain Css. Some drugs also have non-renal clearance channels, but the main point remains: diminished kidney function lowers clearance and can lead to accumulation if dosing isn’t adjusted.