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