I understand why water-soluble substances can be excreted. However, why are they easier to excrete than lipid-soluble substances? Why can’t lipid-soluble substance be excreted just as easily in the kidneys?


Short answer
If you understand why hydrophylic compounds can be excreted, than it's kind of straightforward why hydrophobic ones can't - because they are not hydrophylic.

The kidneys, through the production and excretion of urine, are the major gateway of clearing the body from toxins. Some toxins absorbed in the gastrointestinal tract can be excreted by the liver through the gall system.

Urine is watery and kidney's excrete water through ion homeostasis. Hydrophobic compounds do not dissolve in water and hence cannot be excreted by the kidneys. The liver has an important role in making hydrophobic toxins water-soluble. Often hydrophilic groups are attached to it in the liver, making them hydrophilic. If that can be achieved, they can be excreted through the kidneys. Hydrophobic compounds that are resistant to chemical modification tend to accumulate in the body in fatty tissues like the nervous system, for example the notorious polychlorinated biphenyls (PCBs).

- Chen. Activation and Detoxification Enzymes: Functions and Implications, Springer Science+Business Media (2012)

  • $\begingroup$ I guess what I’m wondering more about is what happens to those hydrophobic compounds that can’t be excreted. (Even if this doesn’t happen and the body makes sure they’re made more water-soluble, let’s say hypothetically it happens.) What happens to these substances then, if they aren’t dissolved in the urine? $\endgroup$ Nov 7 '15 at 13:26
  • $\begingroup$ I should add that by my previous comment, I meant what happens to them as they pass through the nephrons of the kidney. They still move through the nephrons, right? Then what happens, if they aren’t flushed out? $\endgroup$ Nov 7 '15 at 13:35
  • $\begingroup$ They accumulate, as said above $\endgroup$
    – AliceD
    Nov 7 '15 at 13:47
  • $\begingroup$ @lightweaver -They are, as AliceD stated, changed into more hydrophilic substances in the liver, then excreted, often through the biliary tract or the kidney. $\endgroup$ Nov 7 '15 at 20:59
  • $\begingroup$ @AliceD I understand they accumulate as fatty tissue in other places of the body. But I’m just not seeing how they end up as fatty tissue elsewhere if there isn’t a mechanism by which they are saved from being excreted in the kidney, so to speak. What happens to the fat-soluble compounds as they move through the nephrons? Accumulate within the kidney? (And if this entire scenario doesn’t happen, then hypothetically what would happen if it did?) $\endgroup$ Nov 8 '15 at 1:16

If I've interpreted your question right then I think this is the answer..

You have both lipid-solule and water-soluble in the filtrate.

Lipid-soluble substances can easily cross the phospholipid bilayer of cells lining the tubules and so are extensively reabsorbed by passive diffusion. Thus the kidney cannot actively excrete lipid-soluble substances. This means the kidneys cannot alter the plasma concentration of these substances.

Water-soluble substances are effetively trapped in the tubules. This means the kidneys can selectively secrete or reabsorb water-soluble substances via channels etc. So the kidneys can only control the excretion of (and actively concentrate in the urine) water-soluble substances.

Sorry I don't have a reference for you but you've probably already found an answer anyway since this was originally posted a year ago.


You need to understand how renal ultrafiltration works to answer this question.

In the glomerulus, hydrostatic pressure forces fluid (filtrate) across 3 barriers into the collecting tubule. The first is the membrane of the glomerular capillary, which has fenestrations (pores) which are about 8um wide; only molecules smaller than 8um and\or molecules that can diffuse across a lipid bilayer will pass this membrane.

Next, they must pass the glomerular basement membrane, which has a slight negative charge. Any negatively charged molecules will be repelled and not excreted.

Last, they must pass through the filtration slits formed by the interdigitations of podocytes that are applied to the glomerular basement membrane. This is also a very narrow passage and has a slight negative charge.

Now, none of those seems to immediately preclude hydrophobic molecules from passing through the glomerulus... but how do they get there? They have to be dissolved in blood! But that's impossible if they're hydrophobic- physiologically hydrophobic molecules are usually bound by proteins, which are hydrophilic but often have hydrophobic regions. Albumin is the classic example, and albumin is just slightly too large to pass through the filter. There is no carrier system that allows hydrophobic molecules to be shuttled to the glomerulus and then dumped off to be filtered.

  • 1
    $\begingroup$ Brian thanks for your effort on this answer - please add some references so that other users that are unfamiliar can understand what you're talking about and can read further if necessary $\endgroup$ Feb 17 '17 at 2:35

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