LETTER TO THE EDITOR
Year : 2012 | Volume
: 23 | Issue : 2 | Page : 361--362
Concerns regarding laboratory analysis of urine protein: A brief comment
Wiwanitkit House, Bangkhae, Bangkok, 10160, Thailand
Wiwanitkit House, Bangkhae, Bangkok, 10160
|How to cite this article:|
Wiwanitkit V. Concerns regarding laboratory analysis of urine protein: A brief comment.Saudi J Kidney Dis Transpl 2012;23:361-362
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Wiwanitkit V. Concerns regarding laboratory analysis of urine protein: A brief comment. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2021 Apr 16 ];23:361-362
Available from: https://www.sjkdt.org/text.asp?2012/23/2/361/93179
To the Editor ,
Urine protein is an important indicator of renal disease. Laboratory analysis of urine protein has become a widely used and important investigation in medicine at present. However, overt proteinuria that is detected on classical urinalysis usually means an irreversible pathological process. Hence, a screening test to detect renal disease at an early stage, namely a test that can detect small levels of protein in the urine is needed. There are several new-generation urine protein tests at present including tests to detect microalbuminuria as well as albumin/creatinine ratio (ACR). In this letter, the author will specially discuss some laboratory concerns regarding analysis of urine protein.
Issues on urine sample collection
An adequate urine sample is required for laboratory analysis of urine protein. As a rule in laboratory medicine, the preanalytical quality concern is very important since most errors occur in this stage. A clean voided urine sample is recommended for urine protein analysis. As a standard reference test, a 24-hour urine sample should be used. However, this is usually not comfortable and poor compliance from patient in specimen collection can be expected. There are many reports concerning the use of shorter period urine samples for analysis. Wiwanitkit recently reported that "the alternative four-hour sample, gives the maximum effectiveness in the shortest period of turnaround time. Hence, this alternative is recommended for screening pro-teinuria."  However, a single test by a urine strip is also used as a rough screening for urine protein in clinical practice. It is accepted that "spot urine samples can be used for screening patients for albuminuria and proteinuria."  Focusing on the practice of time-related urine sample collection, there is a common question on the need for refrigeration of the urine specimen (kept at 4°C). The possible question seems to be: (a) "If not refrigerated, can it be a problem?" and (b) "If refrigerated, can it be a problem?" Generally, the urine sample has to be fresh for analysis since, if the specimen is kept for more than 15 minutes, there will be fermentation and a false increase of bacteria and nitrite can be expected.  This will result in increase in urine protein which is a byproduct of this process. Some authors had also raised the concern that refrigeration might cause cell destruction. However, there is a recent paper mentioning that this is not a major problem.  Horton indicated that "refrigeration of urine samples for up to 24-hours in the hospital setting rarely causes changes in identified organism type and causes no clinically significant changes in urinalysis or urine culture results." 
How to measure in screening for urine protein level?
The technique to be adapted to measure low levels of protein in the urine is an important factor. Gallagher et al concluded that "the advanced techniques are superior to traditional screening procedures in detecting abnormal urine composition. It is suggested that traditional uri-nalysis should be supported or replaced by quantitative determination of albumin."  For the quantitative determination of protein in urine, there is another important concern. Recently, Brinkman et al concluded that "the higher prevalence of microalbuminuria, accompanied by a similar absolute risk for peripheral vascular disease compared to patients with micro-albuminuria detected by nephelometry, suggests HPLC to identify more people at risk, which is of great importance, especially when screening in large populations is concerned."  However, in real practice, HPLC is used as a reference test and the immunological test is still widely used in routine practice. The use of immuno-chromatographical test (urine strip) accompanied by urine strip reader machine is common. It should be noted that, although there are some urine strips (such as Micral test) that can be used for determination of urine protein with the naked eye, these strips are not considered good quantitative tests since they can read only urine protein level without relative comparison to urine creatinine. Indeed, the standard practice should be the use of urine strip for monitoring the urine ACR.
What to measure in screening for urine protein level?
As noted earlier, it is not presently acceptable to detect gross albuminuria or proteinuria by classical urinalysis strip (urine protein level >300 mg/day) since this is of no use as a screening test.  Microalbumin, urine protein level between 30 and 300 mg/day, is presently recommended.  However, presently there is a paradigm shift to the use of ACR.  The reasons for this shift are as follows: (a) ACR can provide an estimate of daily urinary albumin excretion; (b) accurate microalbuminuria cannot be detected on a conventional urinary protein dip stick on a single urine sample and, (c) ACR can detect lower than 30 mg/day protein in the urine that is not detected by the microalbumin strip test. ACR measurement is recommended using an early morning urine sample where possible, and an abnormal initial test requires confirmation by repeat testing.
However, an important concern in selection of a method for urine protein test in routine clinical practice is the cost. The most appropriate test should be selected based on the cost effectiveness.
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