Renal Drug Excretion
How the kidneys eliminate drugs through glomerular filtration, tubular secretion, and reabsorption.
The Kidney as Excretory Organ
The kidneys are the primary route of excretion for water-soluble drugs and metabolites. Each kidney contains approximately one million nephrons that filter, secrete, and reabsorb drugs through three distinct mechanisms.
Three Mechanisms of Renal Excretion
Glomerular Filtration
Blood enters the glomerulus under pressure, and molecules smaller than ~20 kDa pass freely into Bowman's capsule. The glomerular filtration rate (GFR, normally ~120 mL/min) sets the upper limit for passive renal clearance. Only unbound drug is filtered — protein-bound drug remains in the blood.
Tubular Secretion
Active transport in the proximal tubule moves drugs from peritubular capillaries into the tubular lumen against concentration gradients. Two major transporter families handle this:
- Organic anion transporters (OAT1, OAT3): secrete penicillins, methotrexate, NSAIDs, uric acid
- Organic cation transporters (OCT2, MATE1/2): secrete metformin, cimetidine, procainamide
Tubular secretion can clear even protein-bound drug because binding equilibrium shifts as free drug is removed. This is why penicillin clearance exceeds GFR.
Tubular Reabsorption
As filtrate concentrates along the nephron, drugs may passively diffuse back into the blood. Lipophilic, un-ionized drugs are reabsorbed most efficiently. Urine pH manipulation exploits this:
- Alkalinizing urine (sodium bicarbonate) traps weak acids like aspirin in ionized form, accelerating excretion — used in salicylate overdose
- Acidifying urine theoretically enhances elimination of weak bases, though rarely used clinically
Measuring Renal Function
Creatinine clearance (CrCl) and estimated GFR (eGFR) guide dose adjustments. The Cockcroft-Gault equation remains the standard for drug dosing:
CrCl = [(140 - age) x weight] / (72 x serum creatinine) x 0.85 if female
Clinical Implications
Drugs requiring dose adjustment in renal impairment include:
- Aminoglycosides: narrow therapeutic index, nephrotoxic
- Metformin: risk of lactic acidosis if eGFR < 30
- Digoxin: 60-80% renally excreted unchanged
- Lithium: entirely renally excreted, dehydration causes toxicity
- DOACs: dabigatran 80% renal, rivaroxaban 33% renal
Key Takeaways
- Renal excretion combines filtration (passive), secretion (active), and reabsorption (passive)
- Only unbound drug undergoes glomerular filtration
- Tubular secretion can exceed GFR by clearing protein-bound drug
- Urine pH manipulation can accelerate excretion of weak acids and bases
- CrCl/eGFR guides dose adjustments for renally cleared drugs