Why is finding protein in my pet’s urine a cause for concern?
Protein is a precious resource for the body, and the kidneys have an important role to prevent it from being lost in the urine. The presence of protein in urine is called proteinuria, and it may indicate that the kidneys are not working properly. In some situations, it may even be a sign of kidney failure.
Proteinuria is a common finding on screening lab work and may signal significant underlying disease in dogs. Therefore, it is crucial to investigate proteinuria and, if determined to be renal in origin, to start appropriate medical management. Effective treatment of renal proteinuria in dogs can improve clinical outcomes and help affected dogs live longer, healthier lives.
Proteinuria is a commonly identified abnormality in dogs and can occur due to a number of disease and physiologic processes. Overt proteinuria (UPC > 0.5) has been found to occur in 11-13% of apparently healthy elderly dogs,1, 2 emphasizing the importance of screening for proteinuria routinely so that any underlying disease states can be diagnosed and treated. Proteinuria associated with chronic kidney disease has been consistently shown to be a negative prognostic indicator. It is associated with a higher incidence of uremic crisis and death in CKD patients.3 Diagnosis and control of proteinuria thus may have significant implications for the health and longevity of dogs.
In dogs with glomerular disease with severe proteinuria, hypoalbuminemia, or significant azotemia despite standard treatment, immunosuppressive therapy could be considered to treat possible immune complex glomerulonephritis.17 In a large study of renal biopsies from patients with suspected glomerular disease, approximately 50% had immune complex glomerulonephritis.18 This indicates that roughly half of patients with glomerular disease may benefit from immunosuppression. Since the prognosis of proteinuric patients with severe hypoalbuminemia or azotemia is poor, in these patients, the potential benefits of immunosuppressive therapy may outweigh the risks.17 The treatment of choice for glomerulonephritis in dogs is mycophenolate, given at a dose of 10 mg/kg every 12 hours. A rapidly tapering course of prednisone (1-2 weeks) could be considered in some severe cases as an induction agent, although prolonged therapy with prednisone is not recommended due to the high rate of side effects and potential to worsen proteinuria.19 In any case in which immunosuppressive therapy is considered for treatment of glomerular disease, the client should be fully informed about all potential risks and benefits of this approach.
Although previous guidelines recommended treatment of proteinuria when the UPC was persistently >2 in stage I CKD patients and >0.5 in stages II-IV CKD patients,9 current IRIS recommendations are to treat any persistent proteinuria with UPC >0.5 regardless of stage.10 A renal diet is recommended for any patient with significant renal proteinuria, as feeding a renal diet has been shown to improve UPC and blood pressure in proteinuric patients receiving concurrent medical therapy.11 Initial drug treatment is most commonly with an ACE inhibitor such as benazepril or enalapril. Benazepril is typically favored as, unlike enalapril, it is not renally excreted; however, enalapril is still a reasonable choice for non-azotemic patients. These drugs reduce proteinuria by inhibiting angiotensin-converting enzyme (ACE), which prevents the production of angiotensin II. This leads to dilation of the efferent arteriole and subsequent reduction in the filtration pressure across the glomerulus. ACE inhibitors are typically started at a dose of 0.5-1 mg/kg/day and gradually increase over time pending response. Because ACE inhibitors may reduce glomerular filtration rate (GFR) and also commonly cause hyperkalemia, monitoring of creatinine and potassium is required when using these medications. Monitoring of blood pressure, creatinine, and potassium should be performed one to two weeks after starting an ACE inhibitor and one to two weeks after each dose increase to ensure that it is well-tolerated. ACE inhibitors may take time to reduce proteinuria, so rechecking UPC is not usually done until about one month into treatment or after each dose change. Doses of 2 mg/kg/day may be required to provide an adequate response, although the development of hyperkalemia or azotemia may limit the ability to increase to this dose.12
Initial diagnostic evaluation of proteinuria should include a urinalysis, urine protein: creatinine ratio (UPC), complete blood count, and chemistry panel, as well as infectious disease testing relevant to the area and the dog’s known travel history.5 Multiple infectious diseases have been associated with proteinuria in dogs, including Lyme disease, Anaplasmosis, Ehrlichiosis, Leishmaniasis, Leptospirosis, and rickettsial infections, among others.6 Urine culture is also routinely performed in dogs with proteinuria to rule out occult urinary tract infection, although recent evidence suggests that the prevalence of occult UTI in dogs with proteinuria is low (<3%). This indicates that urine culture may not be required in proteinuric dogs lacking pyuria, bacteriuria, or lower urinary tract disease signs.7 Blood pressure should be measured in all persistently proteinuric patients, as hypertension is both a common sequela of proteinuric kidney disease and may contribute independently to proteinuria by increasing the filtration pressure across the glomerulus. Additional diagnostics, including abdominal ultrasound and thoracic radiography, may be warranted in some patients to evaluate for neoplasia that may result in secondary immune-mediated glomerulonephritis. Ultimately, renal biopsy is recommended for a definitive diagnosis if all other causes of proteinuria are ruled out and the proteinuria is consistently in the glomerular range (UPC >2).5 However, this is performed infrequently due to the risks associated with the procedure and the specialized processing (and associated cost) required for useful results.
Overview of Proteinuria (Excessive Protein in Urine) in Dogs
Proteinuria, in dogs, is the presence of excessive protein in the urine, released from the glomerulus, the filtering unit of the kidney. Normal urine contains only small amounts of protein.
The anatomical structure of the filtering unit of the kidneys restricts the passage of proteins over a certain size. Albumin, an important blood protein, constitutes only a small portion of the protein normally present in urine. Smaller proteins can pass freely through the glomerulus, but are largely reabsorbed by the cells of the kidney tubules.
There are 3 classifications of proteinuria:
There are a number of disorders associated with glomerular proteinuria including:
Diagnostic tests needed to identify proteinuria include:
There are three basic treatment objectives: