Creatinine, Chelationists, & Grading On A Curve

In an earlier post I touched on the problems that can arise when urinary metabolites are normalized to creatinine. It's not uncommon for laboratories, mainstream and not-so-mainstream, to report levels of metabolites and toxins as a ratio to creatinine which should be fairly constant for most people.

But what happens when a patient has consistently decreased creatinine clearance? Might that cause a false elevation in the target analyte? What happens when an entire population shows an average decrease in urine creatinine levels? Might that give an impression that certain urinary compounds and elements are significantly elevated in one group of patients?

There have been anecdotal reports of decreased creatinine in many autistic children for years but, until recently, more emphasis has been placed on the apparent elevations in metals, peptides, organic acids, etc. I say apparent because the possibility that these elevations are really artifacts of lowered creatinine has been largely ignored and in some cases willfully exploited.

Over on the Autism-Mercury Yahoo group one can see parents offering tips on what to do when urine mercury levels don't fall in line with expectations:

"No, not necessarily, you need a normal creatinine to make muscle etc.Creatinine fluxes thruought the day and high creatinine goes with darker urine, lower creatinine is with nearly water colored urine. But in the game we are playing,(for lack of better word) and at times needing to see it on paper, and if you are inclined to "need" to prove to anyone, as usually it only takes one result of a high level to get people to believe you (been there done that) the way to do it, to nail a test with black lines is: Watch behavior and urine color. Darker urine will usually give you the off behaviors, hyper, cranky, moody, when they bounce out of that funk, urine will go clear, that is the urine you want to send, the one following a funky behavior going to clear water colored urine.WORKS EVERY TIME. But it has to precede a dark urine spell.Bottom line you are seeing improvements, moving up the chain of issues that is all that matters. But we all like to "see" what we are doing on paper at times."

And this helpful response:

"It is all just the timing you nailed that test. I bet his mercury excretion was higher with the lower creatinine level. The higher the creatinine goes, the lower the metal excretion will be. Next time you get a urine test, take it when the color is nearly clear, the metel excretion will be greater with the lower creatinine, especially after seeing a spell of darker urine. Works all the time, that is if you are into seeing it on paper, some are, some don't care."

(emphasis added)

I would think any parent would be happy to see less mercury but if the intention is to remove the mercury, and the measure of success is urine levels, I guess it makes sense to do whatever is necessary to get those grades up.

Now that there is one small study to confirm this creatinine anomaly, and hopefully independent confirmation in the near future, how might this impact earlier studies where the authors report elevated compounds and elements? How might this impact the cottage industry that caters to anxious parents and alternative health practitioners?

Spot urinary creatinine excretion in pervasive developmental
disorders

[...]

Our results suggest that the use of spot urine creatinine as a ratio measure when analyzing urine samples from PDD patients may not be the most suitable gauge for total urine concentration. Given the evidence of variability in spot urine samples taken at different times of the day, future studies need to be directed at more closely matching the collection time of samples, or if possible, eliminating such bias by the use of 24 h samples. Efforts should also be directed to utilizing other internal (or external) ratio standards when attempting to quantify urinary compounds in PDD.

Measuring urine porphyrin levels is becoming increasingly popular following the recent paper: Porphyrinuria in Childhood Autistic Disorder: Implications for Environmental Toxicity so naturally there will be questions about the accuracy and usefulness of these tests, especially when they come back negative.

Autism-Mercury Yahoo Group: Urine porphyrins result-- false negative?

Okay, so we ran the porphyrin test thru Lab Corp. It all came back negative and it even came back as low in the coproporphyrins.(result was 5, rr 15-75) Should I assume it was mishandled, or do I need to rethink my son's mercury status? (we will start chelation next week) He has no mercury on hair/blood/urine, but high levels of just about everything else on hair--aluminum, arsenic, antimony, etc, plus his hair minerals are a holy mess. He meets and exceeds all 3 counting rules by far. He is 5.I read Andy's posts on how the sample should be handled. They did give us a light-proof container, but I have no idea if preservative was added. This same lab has screwed up several other very basic tests for us before, so I wouldn't be surprised. Also, they did not measure his creatinine that I can see. I was looking forward to getting a big fat positive so I could say SEE-- THERE'S THE MERCURY!!! For all the people who think I'm nuts (and for myself , I must admit) Anyone else get a negative porphyrin but still get mercury out? Or know anything about LabCorps accuracy with this test??

I bet the problem here is that they used the fly-by-night LabCorp outfit instead of the preferred Doctor's Data lab where the customers could be more likely to receive test results to their liking.

Labcorp:

NUMBER OF EMPLOYEES: Approximately 24,000
ANNUAL REVENUE: $3.3 Billion (2005)

LabCorp is one of the world's largest clinical laboratories. LabCorp is also listed on the S&P 500. We offer a broad range of routine and esoteric/genomic assays, and test more than 360,000 specimens daily for over 220,000 clients nationwide.

Speaking of Porphyrins, parents who subscribe to the Autism-Mercury group have been measuring porphyrins as far back as 2000 but some members didn't know how to get the desired creatinine results by timing urine collection.

Porphyrin results - question for Andy?

"The lab commented that urine collections and results in August and November 2000 were not reliable because the creatinine levels were too low - ie below the (adult?) reference range. Just recently, for the March 2001 results, I purposely collected urine first thing in the morning to try and get the creatinine level up to "normal".They were prepared this time to confirm that the liver is under some disturbance."

Fortunately Andy Cutler is there to correct this error in judgment:

Remember that it is very easy for sample handling errors to lead to lower numbers than are really there.

You know, I'm wondering about all of these tests that are supposed to indicate mercury toxicity. What if elevated metals, organic acids, porphyrins, etc. aren't actually elevated at all in these kids? What if they only appear elevated when expressed as a ratio to urine creatinine levels? What if these kids are no more toxic than the next kid and the whole hypothetical mercury-autism thing is one big house of cards?

No, I refuse to believe that all of these doctors, parents, and testing labs have intentionally deceived the public. I know many of these people and they have only the best intentions.

Of course it's possible that the deception was unintentional and simply a desire to see progress on paper.


Further reading:

Urinary Creatinine Concentrations in the U.S. Population: Implications for Urinary Biologic Monitoring Measurements

[...]

For an individual, the creatinine-adjusted concentration of an analyte should be compared with a "reference" range derived from persons in a similar demographic group (e.g., children with children, adults with adults) . For multiple regression analysis of population groups, we recommend that the analyte concentration (unadjusted for creatinine) should be included in the analysis with urinary creatinine added as a separate independent variable. This approach allows the urinary analyte concentration to be appropriately adjusted for urinary creatinine and the statistical significance of other variables in the model to be independent of effects of creatinine concentration