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March 10, 2003


Question from a pediatrician in Chicago, Illinois, USA:

I have not been able to find data about the day-to-day, or diurnal (time of day effects) variation, or effects of activity level on microalbumin measurements. As a pediatrician making decisions about ACE inhibitor therapy, it is necessary to have more confidence about beginning such treatment based on microalbumin measurements. Do you know of a reference to data that has been collected systematically to address the above questions? Should three 24-hour urine collections be done in succession or each separated by a week?


There is some day to day and diurnal variation in microalbumin excretion, but it is very small in relation to the difference between normal and abnormal values. Likewise, it is not surprising that you have not been able to find this information first of all because it is not really relevant, and also there are so many ways of assaying microalbumin.

Perhaps the easiest answer to your question is to say what is done at our center. To begin with collections, so far as possible, are 12 hour overnight ones. This avoids the rather small effects of fluid intake and minimises timing errors when the results are expressed as micrograms per minute of albumin. It is also less burdensome to the patient. All assays are done on a DCA 2000 instrument which measures creatinine too, and it is also approved by CLIA (Clinical Laboratory Improvement Act) as a ‘waived’ test which means it can be carried out by almost anybody. Against this background, normal values are those that are less than 7.6 micrograms per minute of albumin, borderline levels are 7.7-20 micrograms per minute, and abnormal levels are 20-200 micrograms per minute.

ACE inhibitors would not be considered until there had been two consecutive abnormal results. Thus the broad band of borderline results obviates the need to consider diurnal variation. For a few noncompliant subjects, an alternative is to measure the microalbumin/creatinine ratio in a random sample.

In the now rather unusual event that you suspect microangiopathy in a poorly controlled young teenager, the albumin excretion rate should be corrected for surface area.

Additional comments from Dr. David Schwartz:

Do whatever screening test you like (random urine microalbumin/creatinine ratio or more quantitative 24 hour or 12 hour microalbumin excretion screen). If normal, it’s normal.

If abnormal, then you must do a quantitative study. While there is really no “diurnal variation” (to my knowledge), there is a litany of issues that can lead to non-pathologic microalbuminuria, as you know including orthostatic proteinuria, illness, fever. etc. The 24 hour urine collection remains the gold standard.

If you start with that as your “screen” and it is abnormal, and then the repeat is abnormal, then I think you start your ACE inhibitors. If I’ve thought that the child has had good glycemic control with good hemoglobin A1c values and I then surprised at the results of the microalbumin excretion, I send them for renal biopsy to exclude “something else” before starting the ACE. If they have not had good control, then I just start the ACE.

If the qualitative screen is abnormal (i.e. microalbumin/creatinine ratio), and the 24 hour or overnight 12 hour is abnormal, I follow the same plan above.

Personally, in order to try to circumvent the entire issue of orthostatic proteinuria, I ask my patients for the overnight urine collection.

Additional comments from Dr. Larry Deeb:

I think we do know that protein excretion is greater when standing than lying down. I do overnight levels per milligram of creatinine when I get an abnormal spot. I am aggressive so readily treat.