February 12, 2010
Question from Jackson, Wisconsin, USA:
My 14-year-old son, who has type 1, had a syncopal episode at school. His blood sugar was checked immediately and was 200 mg/dl [11.1 mmol/L] (the Humalog did not peak yet from breakfast). He had an illness a few weeks prior to this event that caused high fever, night sweats, cough, insulin resistance, and a complication of inflamed lungs at the end of the illness. He was treated with azithromycin, twice, during the illness and Prednisone, 50 mg, for five days, following the fever and insulin resistance. We kept in close contact with the pediatrician and diabetes team. He seemed fine the morning he went to school. My son also was on enalapril, 5 mg, one at bedtime. He started taking it a few years ago for microalbuminuria (they checked random and multi-hour collection levels). His last test was August 2009 with: Microalbumin/creat. ratio at 72 and Microalbumin at 13.7. History: A couple of years ago, my son had an illness that caused his blood pressure to drop drastically for about a month. He was seen by a cardiologist who felt the bottoming out of the blood pressures was residual from the illness. He stopped the enalapril during the illness and resumed after his blood pressure stabilized. We were advised and continued skipping the enalapril when he was ill (since he does tend to drop in blood pressures, and doesn't have a very high blood pressure to begin with). With this last illness, I thought he was fine so I resumed his enalapril. This was the night before his syncopal episode. We have been working with multiple medical teams now, since we went to the Emergency Room (ER) and had further evaluation. The cardiologist who evaluated his EKG informed my son's pediatrician that his LVH (left ventricular hypertrophy) was benign due to his athletic lifestyle (he also had sinus bradycardia). The cardiologist then wondered if the microalbumin that was seen in the urine was a result of my son's sports' activities rather than kidney issues from diabetes and is questioning if the enalapril is necessary. I tried to find information about the difference of microalbuminuria from diabetes and from being active, but my attempts have been unsuccessful. The nephrologist feels the enalapril is necessary and did not cause the syncope (even though that was the ER's diagnosis). The nephrologist is recommending a thorough cardiac evaluation, which we have scheduled. I guess it is a bit confusing now. Both doctors are very intelligent and respected and make great points. The diabetes team and pediatrician are also in the mix, but are not as involved in the decision making as the previous mentioned specialists. I just would like to be more informed so we can make educated decisions, ask intelligent questions at the upcoming appointments, and prevent another syncopal episode. Our son is slender (98 pounds), played football in the fall and is now on a basketball team. Any insights or information would be greatly appreciated.
Thank you for posting your interesting and thoughtful question.
First of all, it does sound that you son’s health team members are thinking much about matters. Please be certain that they converse with one another, also. You might wish to ask for a “Care Conference” with all of them together. That takes a lot of coordination and someone has to take the helm at leading that. It might be you. Better yet, your pediatrician or his/her staff.
It is frustrating when you get medical opinions that do not completely agree.
I had an athletic patient with well-controlled type 1 diabetes (no HbA1c greater than 7.5% and most in the 6% range) on an insulin pump for years who had massive amounts of protein in the urine, tested multiple times in multiple ways (see below) in order to try to exclude his athleticism as a major factor. I sent him to the pediatric nephrologist for a kidney biopsy because I didn’t believe that all the protein was “simply” from the diabetes, given his overall excellent glycemic control. But, the nephrologist did not perform a biopsy and relayed it all to diabetes and simply “pushed” medication treatment (along the lines of the enalapril used for your son). The urine albumin did not improve and I continued to ask the nephrologist and the family to “strongly consider” a biopsy. The nephrologist did not and the family, wishing (understandably) to avoid a procedure, opted to heed that decision. I could not force the biopsy but the young man’s microalbumin only worsened. I since relocated and do not know what eventually transpired. (I did present the Case Scenario at a regional pediatric endocrinology meeting and got consensus from the attendees that a biopsy was in order.)
So, as you probably know, “microalbuminuria” refers to a very small range of the protein called albumin in the urine. Normally, there should be essentially “no” albumin in the urine. As proteins go, albumin is a relatively large molecule and the kidney “waste-filtering process of the blood” should not allow albumin to “leak” into the urine. But sometimes, a small amount does. This is called “microalbuminuria” and has specific quantitative definitions:
a random, “spot,” urine test should have a ratio of less than 30 MICROgrams of albumin per gram of creatinine (another waste product) OR
in a carefully timed and collected quantitative urine specimen, the amount of albumin should be less than 30 MILLIgrams of albumin per 24 hours OR
in a carefully timed and collected quantitative urine specimen, the amount of albumin should be less than 20 MICROgrams per MINUTE.
The values that you gave in your letter (“Microalbumin/creat. ratio at 72 and Microalbumin at 13.7”) are discrepant. The ratio is abnormal but the second value is normal IF YOU ARE DESCRIBING A CAREFULLY TIMED COLLECTION, but no measurement units were given. But the careful quantitative technique is thought to be more sensitive than a “spot/random” collection with the ratio to creatinine.
As alluded, there are several things that can lead to microalbuminuria including concurrent fever, very recent illness, and moderate to vigorous activity. There are benign and transient conditions that relate to being upright or laying down (“orthostatic proteinuria”). There are various serious kidney diseases; there are conditions, such as diabetes mellitus, whereby microalbuminuria is a prelude to a potentially more serious issue (as you know); there are rare anatomic issues having to deal with the anatomy of the blood vasculature feeding and draining around the kidneys. There are others.
The MOST SPECIFIC and SENSITIVE way to assess for true kidney disease AND diabetes-related kidney disease is a kidney biopsy with a needle. The patient is awake (may be slightly sedated), his skin is numbed up with novacaine-type medication, and the expert physician in this technique (usually a nephrologist but could be a radiologist) uses a special needle to “stab” a kidney (through the skin) in order to obtain some biopsy specimens. These are looked at under the microscope after special preparation. A special very powerful microscope, called an electron microscope should also be use to examine for specific details. But clearly, such a procedure has risks and is expensive and certainly not everyone (or every diabetic patient) needs to have this. So,”screening tests” have been devised, such as the spot urine and timed urine collection procedures described above.
A common strategy would be to first screen with a random/spot urine albumin/creatinine ratio. If the value is normal, then the screen is passed (“a negative test”). If the value is more than 30 mcg/gm, then the test is failed (“a positive test;” weird terminology, isn’t it?!?) and a more specific quantitative test is done next. This used to be a complete 24 hour urine collection, but these are cumbersome. So, many clinicians adjusted this to be “near 24 hours” or “12 hours” or some other specific time frame. As long as the patient CAREFULLY collected the urine and PRECISELY noted the duration of a collection, then the values could be calculated and extrapolated (per 24 hours or per minute). In order to by-pass the potential for interfering issues related to being ill or upright or active for long before the collection, some clinicians prefer a collection obtained first thing in the morning (timed from the night before) after the patient had a quiet, non-active day (the day before) and was lying in bed overnight (asleep) for at least eight or more hours.
Furthermore, it is recommended that abnormal tests be repeated at least twice for confirmation (and some clinicians would confirm three separate times). ON THE OTHER HAND, many of our endocrinology colleagues who care for adults (and some pediatric providers also) will simply begin medications, such as enalapril, “automatically” in an effort to “protect” the kidneys from diabetes-related kidney disease, even is the test values are normal.
Based on the information you provided, I am not certain that your son fits a complete definition of microalbuminuria; of course, I don’t have the values from the urine tests of several years ago. I don’t think I saw where you provided his degree of glycemic control by noting his various HbA1c results, but it may be worthwhile to have your specialist consider a trial of several days to weeks OFF of the enalapril and then repeating the tests with consideration for careful urine collections as described above when your son is not ill and has been purposefully not active. Another alternative, especially since your son has been on treatment for the microalbumin for a few years – again more specific but more invasive – would be to have a renal biopsy done. Ultimately that will be the most definitive test.
By the way, I can understand that your athletic son might have left-ventricular hypertrophy (LVH) but I totally agree with a careful pediatric cardiology assessment. I am not so comfortable that an athletic 14-year-old should have “low” blood pressure normally. Also, obviously, at 98 pounds at age 14 to 15 years, especially depending on his height, your son is on the low-weight side. Are you sure his diabetes is in good control?
One last thing about timed urine collections. Let me review the PROPER technique. First, choose the time you will begin. Let’s say 10 p.m. At that time, the patient goes to the toilet and EMPTIES the bladder and FLUSHES it away! THAT urine is NOT part of the collection, given that it was produced and stored in the bladder several hours before after the last urination. But, after the bladder is emptied, then ALL subsequent urinations until AND INCLUDING the designated time is complete (say NOON) are collected in the specified container. The times of the beginning and end of the collection are noted (10 p.m. to noon) and you have a properly timed 14 hour collection. (It is common for patients to say that they will start collecting at a specific time but not empty the bladder [or empty the bladder into the collection container] and thus skew the sample and the mathematics for calculation.)
Let us know what you find.