Protein: There are many different ways to measure urine protein. One might check a "spot" urine (test done on a random specimen) or a timed urine (up to a 24-hour collection). One might test generally for "protein" or more specifically for types of protein. And one might use one of many different test methods, including urinary protein electrophoresis (UPE) on concentrated urine. One cost-effectiveness study¹ suggests that one either screen test adults infrequently (such as every 5-10 years) or selectively (those age 60 or older; or those with hypertension).

Microalbuminuria is found in 6% of the general population & tend to reflect hypertension, kidney disease, or diabetes.

Our main hospital lab uses the "Chemstrip IRIS" system for automated reading of test reactions. This method detects urine protein by the "protein error of pH indicator", a phenomenon discovered in 1909 by Sorensen. In the presence of protein, the test's dye indicator changes from a yellow color to light green (the system is more sensitive to albumin than to Bence-Jones and other proteins). It should be thought of as an albumin test. Most such methods detect albumin in urine at levels of 15 mg/dl or higher; it is said that a typical "normal" series of urine specimens in a normal person should average less than 15-20 mg/dl of albumin. The definition of microalbuminuria is 30-300 mg alb/ 24 hours of urine collected. Testing for diabetic microalbuminuria may be important. Expressed another way, normoalbuminuria is less than 30 micrograms of albumin per milligram of creatinine. While microalbuminuria is 30-299 & macroalbuminuria is 300 or higher micrograms of albumin per milligram of creatinine

• causes of false positive reactions:

  • with the IRIS system:

    • strongly basic/alkaline (pH 9 or higher) samples

    • testing while on phenazopyridine therapy

    • testing when undergoing "blood substitute therapy" with polyvinylpyrrolidone

    • when disinfectant residues are present in the container used for the urine specimen collection (chlorohexidine or quarternary ammonium-containing disinfectants)

• causes of false negative reactions:
• causes of proteinuria: posture changes, exercise, fever, and a vast variety of diseases, including the metabolic syndrome.
• Urine protein electrophoresis (UPE): to decide glomerular vs. tubular vs. mixed:
  • >50% albumin suggests a glomerular defect, especially if not much mixed globulins
  • 10-20% or less albumin and mixed globulins suggests primarily tubular
  • in between (21-49%) albumin with mixed globulins, or mildly >50% albumin plus presence of mixed globulins suggests glomerulotubular pathology
• diseases which (unless complicated by other diseases) don't cause proteinuria: generally speaking, they are those diseases that have no effect on the kidneys.

Routinely calculated GFR: In Sept. 2005, our lab responded to nephrologists' requests to have the "GFR estimation" automatically calculate on the chemistry profiles. We used the MDRD equation. We immediately began to get calls from doctors that the estimation was "tagging" too many people with abnormal GFRs who do not have renal disease. Dr. Rule noted that the MDRD was based on people with renal disease and that it found a 12% prevelance of reduced GFR in the general population. However , the Health equation based on normal people only finds a 0.2% prevelance of reduced GFRs. In May 2008 we adjusted our serum creatinine to an international standard for reporting creatinine (somewhat similar to what was done with "prothrombin times" by coming up with the INR). So, as of July 2007, we are hesitant to change our formula. Interestingly the eGFR calculation formula was also changed and eGFR’s calculated from the “new” creatinine levels calculate virtually identical to eGFR’s from the old formula w/ the “old” creatinines, thus eGFR results haven’t changed.

We're not sure of the real utility of all this and think that the eGFR problems noted in our 2007 lab newsletter still remain. Some of the nephrologists are happy with the new lower creatinine cut-off, and we think that separating out a female range has merit, though there’s still no allowance for body habitus, muscle mass, etc., thus still a role for measured creatinine clearances.

References:

1. Boulware LE, et. al. "Screening for Proteinuria in US Adults", JAMA 290(23):3101, 17 Dec. 2003.

2. Rule A, Mayo Clinic Proceedings, Nov. 2006.