The protein pad on the multireagent dipstick (Multistix®, illustrated above) is based on the "protein error of pH indicator dyes". Basically, the test is dependent on the ability of amino groups in proteins to bind to and alter the color of acid-base indicators, even though the pH is unchanged. The reaction is extremely sensitive to albumin (as it contains the most amino groups), but is much less sensitive to globulins. It is insensitive to Bence-Jones proteins. Generally this differential sensitivity is not a significant problem (nearly all cases of significant proteinuria involve albuminuria).
The table below illustrates how results from the dipstick (Multistix) correlates to those from the Criterion, the machine used to "read" the dipstick at Cornell University.
The urine protein results should always be interpreted in context with the urine specific gravity and pH. Normal urine contains little protein; negative to trace reactions are usual in concentrated urine. A trace to 1+ reaction in a very dilute urine is suggestive of significant proteinuria. A dipstick protein reaction > 2+ in concentrated or dilute urine indicates significant proteinuria. There are numerous causes of proteinuria, the most common of which are urinary tract inflammation, hematuria, and glomerular disease. False positive and negative results also occur. Note that the dipstick protein only provides a subjective measurement of the degree of proteinuria. A more accurate assessment of proteinuria is obtained with measurement of the urine protein to creatinine ratio.
Glomerular permeability is affected by molecular weight, size, shape and electrical charge of molecules. It is also influenced by renal hemodynamics. In general, the renal threshold is 68,000 daltons, therefore the glomerular filtrate contains electrolytes (in a similar concentration to plasma) and low molecular weight proteins. These filtered proteins are normally taken up and catabolized by renal tubular epithelial cells, therefore altered renal tubular function can result in these proteins being retained in the urine (tubular proteinuria). Alterations in the glomerular barrier from altered renal blood flow (e.g. passive venous congestion in congestive heart failure) may result in mild proteinuria (functional proteinuria), whereas glomerular disease will result in a significant and severe proteinuria, consisting mostly of albumin (pathologic glomerular proteinuria). Increased filtration of low molecular weight proteins that are in high concentration in blood (hemoglobin, myoglobin, Bence-Jones proteins) will result in a significant proteinuria as the high concentration of these proteins in the filtrate overwhelm the renal tubular resorptive capacity (overload proteinuria). Urinary or reproductive tract inflammation and hemorrhage will also result in proteinuria because of the contribution of plasma proteins. More details are given below.
Pre-renal proteinuria (also called overload or pre-glomerular proteinuria)
This occurs when there are large concentrations of small proteins which have molecular weights (MW) below the normal glomerular threshold, e.g. colostral proteins, Bence-jones proteins (free light chain of immunoglobulins), hemoglobin monomers or dimers and myoglobin.. These freely filtered proteins, when in excess, are not able to be completely resorbed by the renal tubules, resulting in proteinuria. A colostral proteinuria occurs in neonatal animals less than 40 hours old. Free light chains occur in excess in animals with plasma cell neoplasia, including extramedullary plasmacytoma and multiple myeloma. Hemoglobinuria will occur in states of intravascular hemolysis. There should be concurrent hemoglobinemia and red urine supernatant (if there is large amounts of hemoglobin) with a concurrent anemia if there is a proteinuria due to hemoglobinuria. Myoglobin will leak into the urine in conditions of severe muscle injury (rhabdomyolysis). Increased values of muscle enzymes (CK, AST) will be seen in chemistry panels from affected animals, although the urine may not be discolored unless the myoglobinuria is severe. Note that both hemoglobin and myoglobin will cause a positive result for heme proteins on the dipstick. But, the protein reaction on the dipstick is less sensitive to hemoglobin and myoglobin than it is to albumin.
This occurs when there are alterations in glomerular permeability (glomerular proteinuria) or inability of the tubules to resorb small MW proteins which are normally filtered into the tubules through the glomerulus. Renal proteinuria also occurs when disease processes within the kidney cause leakage of serum protein into the urine, e.g. hemorrhage, inflammation.
False positive results
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