November 13, 2003
Complications
Question from Illinois, USA:
I’m wondering about the different normal values used by the ADA and others for diagnosing microalbuminuria. In particular, I have read that 24-hour urinary albumin excretion under 30 mg/day is considered normal, yet I have also read that a urinary albumin concentration under 15 to 20 mg/L is considered normal in a 24-hour sample. However, let me cite an extreme example: what happens in a situation (taken to extremes by this example, I admit) where someone has, say, a 30 mg/day urinary albumin excretion (ever so slightly microalbuminuric) but with a 3 L urine volume (thereby having a 10 mg/L urinary albumin concentration, and being in the normoalbuminuric range)?
I’m quite familiar as far as converting between different units of measure (for example, converting between different units of concentration, etc.), but what happens when, using different units (as above) can result in fundamentally different results? Is this a situation at which the point one might consider the possibility of water loading/diuresis causing a false positive, or should the results (if verified on further tests) be considered significant and in the microalbuminuric range?
Lest this question seem too theoretical, no, I’m not a medical student, simply a type 1 diabetic for over 17 years. My last three annual 24 hour microalbumin test results have been (oldest to newest) trace (I believe this was done using the semiquantitive method, bracketed into none/0, trace/20, moderate/50,…), 2.5 mg/L (< 4.3 mg/L normal, a puzzling reference range, though I've found at least one other lab that, at that time, did microalbumin/creatinine ratios using that normal range), and 23 mg/day (< 30 mg/day normal, though my urine volume was approximately 2.5 L over that 24-hour period). The last one, frankly, spooked me, and made me wonder about how one should interpret results where the urine volume is higher than usual. I've had very good control in the past several years (< 7% A1c tests), though it was rather poor earlier in life, thankfully no known complications except what appears to be 'white coat' hypertension (always high in any medical setting, always normal when taken at home, though I'm on an ACE inhibitor for a protective effect and have been for several years now), but kidney disease scares me. My endocrinologist is repeating the test in several months, so we'll see what the result is the next time. I personally feel he is an excellent doctor, and I'm very comfortable with him, but I fear (considering I quiz him half-to-death on every microalbumin result I have) that he'll take offense at some point; I don't want him thinking I'm second-guessing him or playing at being a doctor or somesuch. I don't really know what to expect, other than that as for now I'm apparently 'normal' according to ADA guidelines and accepted best medical practice.
Answer:
Let me see if I can answer this in a way that will seem reasonable to understand. It is true that normal values for albumin excretion should be <30 mg/24 hours. Albumin is more specific for diabetes-related kidney disease than total protein. Total protein has been measured semiquantitatively by dipstick measures. However, by the time a person has dipstick positive urine, the microalbumin test would have been positive for a long time. Therefore, the value of the microalbumin test is that it can be abnormal a long time before the usual dipstick test. The dipstick test becomes positive when the albumin excretion is on the order of 250-300 mg/24 hours. Please note that concentration is not usually used as the accepted units for defining microalbuminuria. The reason for this is that your hydration state may have a lot to do with concentration. A very concentrated urine may read differently than a dilute reason. Another way to measure this is with a random urine collection where the units are expressed as mcg albumin per mg creatinine. The normal is less than 30 mcg/mg creatinine. This is a nice compromise for a test because you don't have to battle the problems of performing a 24-hour urine collection. Anyone who has tried to collect a 24-hour urine knows it is full of problems with collecting all the urine. The fact that you have made it 17 years without microalbuminuria suggests that you have already been selected out to be at high risk for developing chronic renal failure. Those patients generally express their risk between 10-15 years duration of diabetes. Now you have some good news to quote. The renal protective effect of ACE inhibitors is greatest in those with hypertension or microalbuminuria or overt proteinuria. It has not been expressly proven to apply to those without any of the above. JTL
