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G. Segev1
1Koret School of Veterinary Medicine, Israel
Dogs and cats may normally have small amounts of protein in their urine; however the term “proteinuria” usually refers to the presence of an abnormal amount of protein in the urine. The term “microalbuminuria” refers to the presence of albumin in the urine in a concentration of 1-30 mg/dL, which is considered abnormal, but is below the detection limit of the urine dipstick. A persistently high magnitude proteinuria is usually an indicator of chronic kidney disease (CKD); however it may be a secondary consequence of infectious, inflammatory, metabolic or neoplastic disorders. Proteinuria is also
a prognostic marker and is associated with a more rapid progression of CKD, a higher frequency of uremic crises as well as an increased mortality rate (1, 2). Thus, early detection of proteinuric animals will allow close monitoring as well as early therapeutic intervention, which may decrease the magnitude of proteinuria
and the disease progression rate of these patients. Screening for proteinuria should be performed in any animal diagnosed with CKD or with any other disease known to be associated with proteinuria.
Methods of detection and interpretation of test results
The urine dipstick colorimetric test is the most commonly used method to screen for proteinuria. The urine dipstick is more sensitive to albumin compared to other proteins, and its lower detection limit is 30 mg/dL. Interpretation
of any result should be done in light of the urine specific gravity. A positive result in highly concentrated urine reflects a smaller degree of protein loss compared to
the same amount of protein in diluted urine; thus, the latter is more alarming. Both false positive and false negative results occur using the urine dipstick. Once persistent proteinuria has been confirmed or when a high magnitude proteinuria is suspected, it should be quantified using urine to creatinine ratio (UPC). Its results are used as a guideline for diagnostic investigation, therapeutic intervention, and monitoring response to therapy. Urine protein to creatinine ratio <0.2 in dogs and cats is considered normal, and a ratio between 0.2-0.4
in cats and 0.2-0.5 in dogs is considered borderline proteinuria.
The origin of proteinuria
Once proteinuria has been documented, its origin should be identified as a first step towards the diagnosis of
the underlying disease. Proteinuria can be classified
as urinary system or extra-urinary system in origin.
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Extra-urinary system proteinuria may result from either pre-renal or post urinary system (i.e. genital system) conditions. Pre-renal proteinuria results from presence of excessive amounts of either normal (e.g., hemoglobin, myoglobin) or abnormal (e.g., Bence Jones) blood proteins, which can be freely filtered through the glomerulus. Thus, pre-renal proteinuria can occur with normal kidney structure and function and treatment
is aimed at identifying and eliminating the underlying disease. Urinary system proteinuria can be classified as renal (functional or pathological) or post renal. Functional renal proteinuria represents a transient change in the permselectivity characteristics of the glomerulus, and thus should not be treated. Pathological renal proteinuria may result from glomerular (decreased permselectivity), tubular (decreased re-absorption) or interstitial (exudation of proteins to the urinary space) abnormalities. Glomerular proteinuria is the most common cause of persistent high magnitude proteinuria. It requires close monitoring, and often warrants diagnostic workup and therapeutic intervention. Post-renal proteinuria relates
to the entry of proteins into the urine from the renal pelvis, ureters, urinary bladder, or urethra, and results from disorders along the urinary excretory system (e.g., infection, urolithiasis, neoplasia).
Diagnostic approach
The diagnostic workup is directed towards the detection of the origin of proteinuria and the underlying disease, and includes complete history and physical examination as well as diagnostic tests such as arterial blood pressure measurement, complete blood count, serum chemistry, urinalysis and urine culture, serologic testing and PCR for infectious diseases, diagnostic imaging, and kidney biopsy. Initially, post renal proteinuria is excluded by evaluating the urine sediment for presence of inflammation and hemorrhage. Then, extra urinary system causes are excluded. Post urinary (genital system) proteinuria is easily excluded by performing urinalysis on urine obtained by cystocentesis, and pre renal proteinuria is ruled out by evaluating the plasma protein concentration and excluding dysproteinemia and presence of specific proteins in the urine (e.g., hemoglobinuria, myoglobinuria and Bence Jones proteins). Glomerular proteinuria can be of any magnitude, but is particularly suspected when persistent high magnitude (UPC≥2) proteinuria is present, and after ruling out extra renal and post renal causes. Glomerular proteinuria can be diagnosed by obtaining a kidney biopsy which can additionally help in sub categorizing the disease, using light microscopy, electron microscopy and immunofluorescence.
Treatment of proteinuria
Therapy of proteinuria should be directed towards elimination of any underlying disease and decreasing the magnitude of proteinuria. Successful therapy

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