Drugs in Renal Failure

Introduction — why the kidney matters for drug handling

• The kidney is the chief excretory organ — renal excretion of unchanged drug is a major elimination route for 25–30% of all drugs; excretory organs clear polar (water-soluble) compounds far better than lipophilic ones, so loss of renal function chiefly threatens water-soluble drugs and their polar (often still-active) metabolites.
• Three renal processes handle drugs — glomerular filtration (only unbound drug filtered, set by GFR & protein binding), active tubular secretion (carrier-mediated — OAT1/OAT3 for acids, OCT for bases; most drugs enter the tubule by secretion, not filtration) and pH-dependent passive reabsorption (ion trapping — alkaline urine speeds weak-acid excretion).
• Secretion governs renal clearance — penicillin (t½ ≈ 30 min) is eliminated largely by OAT-mediated tubular secretion — probenecid competes at the transporter to prolong its level, the classic proof that secretion, not just filtration, drives renal clearance.
• Clinical consequence — any fall in renal function lowers CL_renal; for drugs where renal clearance is a large fraction of total clearance this lowers systemic CL → higher steady-state concentration and prolonged half-life unless the dose is adjusted.