Thursday, 31 March 2011

Specific Gravity vs creatinine for urinary correction

Apologies if you tuned in for a post about autism, but this is another 'other musings' entry (although I might mention autism at some point). Please, stay with me (this is not an April Fool) because I hope it might be of some interest; if anything else it might make for a few factoids vis-a-vie Steve Wright round the water-cooler at work the next day.

What's to say about urine? A waste product that we all produce in copious amounts throughout our lifetime. Constitution-wise it contains quite a bit; a good idea of what and how much is shown here. More recently urine, or rather the analysis of urine has been central to a relatively new branch of biological chemistry called metabolomics - studying the chemical 'fingerprints' left behind by biological processes.

The theory is that the pattern of our waste products in urine for example, whilst being unique to each individual, contains enough information for science to start looking at groupings based on compounds or levels of compounds excreted, which may eventually lead to predictions on our risk of disease or alternate biological markers for particular conditions or diseases.

Don't believe me? Well have a look at these abstracts suggestive of urine markers for kidney cancer, coeliac disease and depression to name but a few.

Last year there was quite a bit of excitement when a team based in London published this paper suggestive of potential urine biomarkers for autism. Accepting a few criticisms of the paper, some of the markers indicated for autism samples such as taurine, glutamate and various potential gut dysbiotic markers have been discussed previously as being possibly relevant, in various biological mediums.

Any more convinced? Yes... No...

OK, back to urine. One of the many differences, both intra- and inter-person, with regards to urine is concentration; that is, how concentrated or dilute our urine is. Urine concentration is affected by many different things; how hydrated our body is, whether we have engaged in any exercise, etc. Concentration of urine is important in working out the total amount of a compound or set of compounds also. If we imagine that a concentrated urine sample will contain higher levels of compounds quantitatively than a more dilute sample, you can see how sample concentration might affect studies looking at quantitative urinary biomarkers for a specific condition.

There are various ways of 'correcting' for urine concentration/dilution. Probably the most widely used is to measure urinary creatinine and correct sample concentration against creatinine. Whilst not wishing to provide Biochemistry 101 for creatinine metabolism, it is important at this point to make a distinction between creatinine and a related compound, creatine (although the two are connected).

So then normally when someone is trying to quantify one or more compounds in urine they may say something like: 100mg compound X / g/l creatinine. This means that 100 miligrams of compound X was detected per gram per litre of creatinine. (There are other units of concentration also used but I will not complicate things).

Creatinine is not alone as a marker for urine sample concentration (spot samples or 24-hour samples). There are others. One measure is the specific gravity (SG) of the sample. Anyone who has an interest in home brewing beer might know something about SG. SG is the ratio of the density of a sample relative to the density of water, assuming equal temperature and pressure. Pure water under set conditions has an SG of 1. A urine sample with all its dissolved compounds should have an SG greater than 1. Before you look away, this is as technical as I am getting.

Measuring the SG of urine is a tried and tested method and, in many respects, an easier option than assaying for creatinine (which depending on your method of analysis can include some quite 'explosive' steps). What's the difference between creatinine levels and SG I thought I heard you say...?

Well, there shouldn't be too much. There has been a long running debate about whether creatinine is a better marker of concentration over SG and vice-versa. The light at the end of the tunnel seems to suggest that there is little or no difference between the two measures when applied to the general population.

Fine, end of story. Not quite. There has been, for quite a few years now, some initial evidence to suggest that levels of creatinine in autism for example, are perhaps slightly aberrant compared to not-autism. Not trying to be a blatant self-publicist here, but I put my hand up because my colleagues and I have published on this a few years back. More recently also, similar findings have been reported by other authors; although I stress that this is not without some controversy.

Why might creatinine levels be unusual in autism? I dunno - potentially lots of reasons ranging from fluid intake to activity levels through to how much meat there is in the diet. What I do know is that if creatinine levels are somehow more consistently perturbed (lower), using it as a concentration corrector might, I stress might, indicate that comparator compounds are present in higher levels than they really are. I will stop there.

Next time you pop to the WC for a sprinkle, take a moment to think about what exactly is going into the bowl and how science stands to gain so much from it.

3 comments:

  1. This comment might be a little off topic but not many people talk about a possible relationship between creatine/creatinine and autism. Just as background, I have three daughters who have autism, two of whom are identical twins. All three have various biological problems to go with their autism but the twins seem to have some disruption in their creatine metabolism.

    We have seen large spikes of creatine in their urine while having normal levels of creatinine (and GAA?). The strange thing is that the levels are not consistent - one time it will be very high and the next time it will be normal - and the consistency doesn't seem to be that related to food intake. Their doctors investigated to see if they have one of the known disorders of creatine metabolism, focusing on a transporter deficiency, but the genetic testing they did turned up nothing.

    So, since you have some experience in this area, I though I might ask if you could perhaps answer a question for me. I have read all of the literature that I could find that focused on disorders of creatine metabolism but I still am having a hard time understanding what how the creatine pathway interacts with other biological pathways. Specifically, I am trying to learn about the relation (if any) to phosphorus, lipids (or cholesterol), and other parts of the energy delivery pathways.

    Is there perhaps a reference work that you might be able to suggest that covers those sorts of topics but isn't so arcane that a (cough) educated layperson has a change of understanding it?

    Thanks.

    ReplyDelete
  2. Thanks MJ. I'm afraid that I am not an expert on creatine per se. From my limited knowledge, I understand that there is bi-directional relationship between urinary creatine and creatinine governed by quite a few things, not least the pH of the urine specimen in question. A good review (although probably one of the longest and most complicated documents I have ever tried to read) is this one:
    http://physrev.physiology.org/content/80/3/1107.full
    It is full-text and covers just about everything to do with creatine / creatinine upto about year 2000.
    I understand also that there is a team based at the University of South Australia who were looking at creatine deficiency syndrome specifically with regards to autism who might be worth contacting also:
    http://www.ncbi.nlm.nih.gov/pubmed/20589913
    This team have quite an interest in urine and autism. Their results in this case did not show anything spectacular in terms of an overall association with autism but they did suggest screening to rule out any relationship in individual cases. If I find anything else, I'll post more.

    ReplyDelete
  3. Thanks for the links. The first document looks to be very interesting.

    ReplyDelete