What Is Excess Protein in Dog Urine (Proteinuria)?
Proteinuria means there is excess protein in your dog’s urine. Although dogs usually have a small amount of protein in their urine, too much protein can be a sign of an underlying condition.
The most important condition associated with proteinuria in dogs is kidney disease, but it can also be caused by infections, inflammation or bleeding along the urinary tract, tumors, high blood pressure, and other conditions. In many cases of proteinuria that are not connected to kidney disease, the condition will resolve as soon as the underlying condition is treated.
Proteinuria caused by kidney disease is a sign that your dog’s kidneys aren’t functioning properly. Kidneys are normally responsible for filtering waste from the bloodstream and balancing levels of certain nutrients.
In dogs with kidney disease, however, a filtering structure in the kidney called the glomerulus is not working as it should. This allows proteins that would normally be kept in the blood to spill over into the urine, where they can be detected by your dog’s vet.
Proteinuria itself is not a disease—instead, it’s a sign there is an underlying condition that needs attention.
The symptoms of canine proteinuria depend on the underlying condition that’s causing it. In many cases, dogs with proteinuria won’t show any symptoms at all, and the condition will be discovered during a routine urinalysis at the vet’s office.
Proteinuria in dogs can be a sign of serious kidney disease, so if you see signs like lethargy or notice that your dog is drinking a lot more, you should seek out emergency veterinarian care as soon as possible.
Proteinuria in dogs may also be associated with any of the following:
The causes of proteinuria include many issues that can occur anywhere along your dog’s urinary tract, including kidney disease.
Urine Protein:Creatinine Ratio
Following detection of proteinuria on urinalysis, quantification using a UPCR may be indicated. The UPCR standardizes protein loss compared to creatinine. This adjusts the amount of protein loss for variations in USG and glomerular filtration rate. A UPCR from a spot urine sample accurately reflects the quantity of protein excreted in the urine over a 24-hour period. A result less than 0.2 is considered normal; a result of 0.2 to 0.5 in dogs and 0.2 to 0.4 in cats is consistent with borderline proteinuria.6 Measuring a UPCR on a single urine sample, averaging UPCRs from 3 consecutive daily urine samples, and pooling 3 consecutive daily urine samples to measure a single UPCR all give similar results.10,11 Therefore, there is no evidence that any individual method for monitoring the UPCR is superior.
To determine if this measurement is indicated, the clinician must (1) document that the proteinuria is persistent and (2) rule out prerenal and postrenal causes. Persistent proteinuria is proteinuria documented on a minimum of 3 urinalyses 2 or more weeks apart. However, if the patient is presenting for a workup of hypoalbuminemia, a UPCR is indicated even if it is the first documentation of proteinuria on a urinalysis. As inflammatory conditions such as pancreatitis can result in transient proteinuria, it is recommended that a UPCR be performed once they have resolved.
Proteinuria can result from urinary tract infections, urinary stones, and other causes of postrenal inflammation; therefore, a UPCR should not be performed in dogs with an active urine sediment or urolithiasis. A negative urine culture should be obtained prior to submitting a urine sample for a UPCR. Although hematuria can result in proteinuria, it should not significantly affect the UPCR unless gross hematuria is present. A UPCR is thought to be an accurate measure of proteinuria in cases with microscopic hematuria but grossly yellow to orange urine.
As previously mentioned, proteinuria is a negative prognostic indicator in dogs and cats with CKD.8 Consequently, every dog and cat diagnosed with CKD should be substaged with a UPCR when there is no evidence of urinary tract inflammation or hemorrhage and dysproteinemias have been ruled out by measurement of plasma proteins. The International Renal Interest Society (IRIS) substaging schematic is included in table 1. It is recommended that patients that are persistently borderline proteinuric be reevaluated within 2 months.
Traditional reagent pad “Dipstick” colorimetric method
This test is most sensitive for albumin but can detect other proteins. This is often the first screening test used to detect albumin. This is a sensitive test, but the results can be falsely elevated with highly concentrated urine or pigmented urine (although the false positive is often no greater than a reading of trace or 1+) since the sticks were designed for human urine which is rarely as concentrated as dog or cat urine. Acidic urine can cause false negative results while alkaline urine can cause false positive results (19). If any protein is detected on a dip-stick, more quantitative assessment of proteinuria is warranted. Performing the sulfosalicylic acid (SSA) test can help delineate between a true and a false positive dipstick test on a concentrated urine sample. A negative dipstick reading in a dog is a reliable indicator of absence of proteinuria, but false negative results are possible with cats (19).
Some laboratories perform this test automatically whenever a dipstick reading is trace or greater. This is a semi-quantitative test for protein and is simple but subject to operator error. The test is performed by using equal parts urine supernatant to 5% SSA in a glass tube and grading protein precipitation based on turbidity. False positive results may occur if the urine contains radiographic contrast agents, cephalosporins, penicillin, thymol, or sulfisoxazole (19). There are fewer false negatives as the SSA test can detect protein at > 0.05 g/L and can detect Bence Jones proteins and globulins (19). A positive SSA test should be followed up with a UP/C determination.
Protein found linking stress and depression
Protein in the urine, particularly when it is of renal origin, can be an indicator of renal damage, and has been found to be associated with progression of renal disease. There are several reasons that protein can enter the urine, through a damaged glomerulus, through lack of reuptake by tubular epithelial cells, and through exudation into the tubular lumen.
Protein in the urine, particularly when it is of renal origin, can be an indicator of renal damage, and has been found to be associated with progression of renal disease. There are several reasons that protein can enter the urine, through a damaged glomerulus, through lack of reuptake by tubular epithelial cells, and through exudation into the tubular lumen. In addition, protein can enter the urine during the collection and storage phase from hemorrhage or exudation in the ureters, bladder, urethra, prostate, or genital tract.
Cause: Strenuous exercise, heat stress, seizures, fever, hemolysis, neoplasia, etc. Indicative of underlying condition and may require additional evaluation
Renal: Indicates pathologic lesions of the kidneys. Can be further classified as glomerular, tubular, or interstitial.
Tubular: lesions that affect the ability of the proximal tubule to reabsorb small proteins that are able to pass through a normal glomerular barrier
Interstitial: secondary to inflammatory lesions of the interstitum that allow protein to exude into the renal tubules
Collection method artifact (blood, discharge from the genital tract), hemorrhage or exudative process from the lower urinary tract (ureters, bladder, urethra, prostate, etc.). Important: studies show that urine must have gross change in color before hematuria can lead to detectable proteinuria and that pyuria must also be significant before it affects the protein on a dipstrip. The Heska ERD test will likely pick up changes earlier than dipstrips in these conditions.
For the purpose of this discussion, we will focus on renal causes of proteinuria, but it is important for the clinician to understand and rule out the non-renal sources in order to avoid misdiagnoses.
MD: macula densa, EA: efferent arteriole, AA: afferent arteriole, B: Bowmans capsule, M: mesangial cell, EN: endothelial cell, BS: Bowmans space, BM: basement membrane, EP: epithelial cell, F: foot processes, PT: proximal tubular cells, G: granular cells, N: sympathetic nerve terminals
Filtration primarily by size (< 60,000 daltons) and charge (positively charged particles move more easily across than negatively charged particles). These layers provide normal permselectivity which prevents large protein molecules from passing through the glomerulus into the urine. When protein is lost into the urine, the proximal tubule cells usually remove it. However, these mechanisms can be easily overwhelmed and this leads to large amounts of protein accumulation in the tubular epithelial cells and in the tubular lumen. This leads In turn to progressive tubular damage and renal disease. This is one of the major theories as to why the degree of on-going proteinuria appears to relate to the rate of renal disease progression.
Damage to the glomerulus and the subsequent breakdown in protein barrier can occur through amyloidosis or immune-complex deposition and damage to the glomerulus (due to chronic systemic inflammation or neoplasia). Proteinuria can also occur in patients with hypertension which increases the intraglomerular pressure and damages the epithelium and basement membrane, allowing protein to pass through.
In patients with chronic renal disease, proteinuria can exist from multiple sources including glomerular damage, hypertension, proximal tubular injury, and exudative lesions secondary to interstitial nephritis and pyelonephritis.Proteinuria has been shown to be an indicator of progressive renal disease. For this reason it is included as a sub-categorization (along with hypertension) in the International Renal Interest Group (IRIS) staging system.
Urine Sediment Evaluation. The presence of casts, red blood cells, white blood cells, bacteria, or epithelial cells may give the clinician a clue to the source of the proteinuria. Proteinuria in the face of an inactive sediment increases suspicion for underlying renal and particularly glomerular disease.
**Some animals may have day to day variations in mild proteinuria due to exercise, heat stress, or physical stress, so it is important to confirm the persistence of proteinuria with a few weeks between tests.
Normal urine with a high specific gravity (> 1.050) can often show trace or 1+ protein on dipstrips. Highly alkaline urine can lead to false positives, highly acidic urine can lead to false negatives. Can be negative in patients with significant proteinuria if the urine is very dilute. Patients with a positive protein level on dipstrip should have a urine sediment evaluated. If inactive, a UPC is indicated.
Normal < 1 mg/dl (cat and dog), test is designed to detect levels of 1-30 mg/dl of albumin. The presence of microalbuminuria may be an indicator of early renal disease but has also been associated with other conditions such as neoplasia, systemic inflammatory disease, and heartworm disease which can lead to glomerular injury through immune complex deposition. May be a good screening test for patients with possible hereditary protein-losing nephropathies (Soft-Coated Wheaton Terriers), risk of renal disease (patients with diabetes mellitus, thyroid disease, or hypertension), and geriatric cats and dogs. If abnormal, follow-up with a UPC to further quantify magnitude of proteinuria.
Normal < 0.4 (cat and dog), allows for correlation of protein content with the concentration of the urine. Pink or red urine can lead to false elevation, as can pyuria (> 3 WBC/hpf). The degree of proteinuria is only very loosely correlated with the type of renal disease and cannot be used to differentiate glomerular disease from amyloidosis. UPC is generally performed if a patient has an abnormal amount of protein in the urine on dipstrip or has an elevated microalbuminuria test.