Renal Tubular Physiology — Drug Excretion

Excretion by kidneys can be influenced by drug characteristics

1) Which affect filtration at glomerulus
2) Which affect secretion into tubules
3) Which affect reabsorption in the tubules

1) Which affect filtration at glomerulus

Filtration at the glomerulus – Dependent on Filtration fraction [GFR / RBF] and net starling force.
Normal filtration is 180 L/day (20% of renal plasma flow)

• Protein binding:
  • Only free drug present in filtered plasma will be excreted.
  • Concentration of filtered drug will be the same as in unfiltered plasma
  • Highly protein bound drugs are poorly filtered
    There is only a weak concentration gradient favouring dissociation from plasma proteins.
• Molecule size:
  • Size:
    • Molecules larger than 30 Angstrom is not filtered
  • Weight:
    • Substances less than 7,000 Da are freely filtered
    • Substances greater than 70,000 Da are essentially impermeable
• Hydrophilic/lipophobic
  Lipophilic drugs may be filtered at the glomerulus but will be freely reabsorbed during their passage down the tubule, such that only trivial amounts are eliminated in urine.
• Charge:
  • Positive ions are filtered (Glomerulus is slightly negative charged)

2) Which affect secretion into tubules

Active process, allows secretion against concentration gradients

• Acid/Base:
  • Saturable process – Saturation may occur of a basic transporter whilst still allowing excretion of acidic drugs, and vice versa.
• Size:
  • Molecules which are too large to be filtered in the glomerulus may still be cleared renally by these mechanisms
• Protein binding:
  • Protein-bound drugs are not cleared this way; only the unbound fraction is available for active secretion.

3) Which affect reabsorption in the tubules

Passive diffusion down a concentration gradient.

• Hydrophilic molecules can only be reabsorbed by a specialised transport mechanism
• Drug ionization:              
  • Only non-ionised drug can be reabsorbed passively
  • Acidic drugs will become ionised in an alkaline urine (and vice versa), reducing their solubility
    This is the physiological justification for urinary alkalinisation.

JC 2019

Answer by JC