How does renal impairment affect drug clearance and half-life?

• A. No effect on PK.
• B. Cl declines, t1/2 increases, and AUC increases; dosing must be adjusted.
• C. Only AUC increases, others unchanged.
• D. Cl increases, t1/2 decreases.

Answer: (B)

Renal clearance largely governs elimination for drugs that are cleared by the kidneys. When kidney function declines, the body's ability to remove drug via glomerular filtration and active secretion decreases, so overall clearance falls. Since half-life is proportional to the volume of distribution divided by clearance (t1/2 = 0.693 × Vd / Cl), a drop in clearance lengthens the half-life (assuming Vd stays roughly the same). At the same time, exposure increases because AUC ≈ Dose/Cl; lower clearance means higher AUC. The net result is greater drug exposure and slower elimination, which raises the risk of accumulation if dosing isn’t adjusted. Therefore, dosing often needs to be reduced or the dosing interval extended in renal impairment.

If a drug’s clearance were to increase, or if half-life were to shorten, that would not align with impaired kidney function, and if the effect were limited to AUC with no change in t1/2 or Cl, that would also not fit the relationship between clearance, half-life, and exposure.