Renal drug elimination occurs through three mechanisms: glomerular filtration, tubular secretion, and tubular reabsorption. Glomerular filtration is a passive process filtering only unbound (free) drug; heavily protein-bound drugs (warfarin 99%, phenytoin 90%) are minimally filtered. The GFR (~120 mL/min) determines the rate of filtration for freely filtered drugs. Tubular secretion is an active, carrier-mediated process in the proximal tubule that can eliminate both free and protein-bound drugs. Two major transport systems exist: organic anion transporters (OATs) secreting acidic drugs (penicillins, methotrexate, furosemide, NSAIDs) and organic cation transporters (OCTs) secreting basic drugs (metformin, cimetidine, trimethoprim). Drug interactions occur when drugs compete for the same transporter — probenecid blocks OAT-mediated penicillin secretion, prolonging penicillin's half-life (historically used therapeutically). Trimethoprim blocks creatinine secretion via OCTs, raising serum creatinine without actually reducing GFR (pseudo-AKI). Tubular reabsorption occurs mainly in the distal tubule and collecting duct for lipophilic, unionized drugs. Urine pH manipulation affects reabsorption of weak acids and bases: alkalinizing urine (with sodium bicarbonate) traps weak acids in ionized form (aspirin overdose — 'ion trapping'), while acidifying urine traps weak bases (amphetamines).