An update on the diagnosis of proteinuria in dogs

Protein losing nephropathy is a common form of renal disease in dogs. Glomerular causes of renal protein loss include glomerulonephritis and amyloidosis. Glomerular lesions have also been associated with underlying metabolic, infectious, inflammatory and neoplastic diseases. Post-glomerular causes of renal protein loss such as hemorrhage and inflammation also contribute to urine protein quantification. Traditionally, urine protein loss has been detected either through a qualitative test such as a urine dipstick or via a semi-quantitative test such as a urine protein creatinine ratio. A urine protein creatinine ratio greater than 0.5-1 is considered abnormal. However, both the dipstick method and the urine protein creatinine ratio can be inaccurate and can yield false positive results due to contamination of urine with red blood cells, white blood cells and bacterial protein and therefore must be measured on urine sample with an inactive sediment and a negative culture. A 24-hour urine protein quantification is more accurate but is technically more difficult to obtain, requiring hospitalization and 24-hour urinary catheterization with a closed collection system.

Table 1: Testing for Microalbuminuria in Clinical Practice

However, a new alternative test is now available to detect proteinuria in dogs and is currently being released for cats. The Heska E.R.D. HealthScreen Canine Urine test is a semi-quantitative test for microalbuminuria in dogs (www.heska.com/erdscreen/erd_studies.asp). The advantages of this test are that it is a point-of-care test which detects small amounts of albumin in the urine prior to the detection of protein via a urine protein creatinine ratio. Microalbuminuria is defined as the presence of albumin in the urine between the concentrations of 1.0 and 30.0 mg/dl (below the detection ability of a urine dipstick test or urine protein creatinine ratio). Thus this provides an earlier indicator of renal damage and protein loss. This test utilizes an anti-canine albumin antibody and therefore is specific for canine albumin in the urine. A secondary advantage is that there is little cross reaction between urine albumin and red blood cells. If macroscopic hematuria is present (i.e. the urine is obviously red in color), then cross-reactivity with microalbuminuria can occur, but this does not occur with microscopic hematuria (Proceedings of the 21st ACVIM Forum, SL Vaden, Microalbuminuria: What is it, and how do I interpret it?). The cross-reactivity of pyuria is somewhat more variable. In one study, 67 percent of dogs with pyuria had urine albumin concentrations less than 1 mg/dl. [Proceedings of the 21st ACVIM Forum, SL Vaden, Microalbuminuria: What is it, and how do I interpret it? Vaden SL et al. J Vet Intern Med 2002; 16:378 (abstract)].

In a large scale study of 3,041 dogs owned by employees of veterinary hospitals, the overall prevalence of microalbuminuria in dogs was 24.7 percent (S. Radecki et al. Proceedings of the 21st ACVIM Forum, abstract #110). In the same study, the prevalence of microalbuminuria was significantly higher in the older population of dogs (4 percent at one year and 55 percent at 15 years). This finding also correlates with the fact that proteinuria occurs in dogs with underlying diseases, which are more common in geriatric dogs. A follow-up study was conducted to survey for underlying diseases in the population of dogs with positive tests. Follow-up information was provided for 572 dogs. Fifty-six percent of dogs were subsequently diagnosed with inflammatory, infectious, metabolic or other disease processes (www.heska.com/erdscreen/erd_data572.asp). These results are also consistent with those found by Whittemore et al., in which 56 percent of clinically ill dogs with microalbuminuria were found to have infectious, inflammatory or neoplastic disease (JC Whittemore et al. Proceedings of the 21st ACVIM Forum, abstract #234). This is an important finding because proteinuria is often associated with underlying disease processes and thus the ERD test can be used as a screening test in older patients as a marker for these underlying processes. Whittemore et al. also demonstrated that this ERD test was more sensitive in detecting proteinuria than the urine dipstick or the urine protein creatinine ratio. In a population of clinically ill dogs, 55 dogs with proteinuria were diagnosed positive using the ERD test but were not detected using a urine dipstick or urine protein creatinine ratio.

Current recommendations for clinical practice are to use the ERD test as a screening test in young dogs of breeds with hereditary predisposition to glomerulopathy. Since there is a marked increase in the prevalence of microalbuminuria in dogs greater than 6 years of age, it may be prudent to begin screening dogs beginning at that age (Proceedings of the 21st ACVIM Forum, S. Vaden "Microalbuminuria: What is it and how do I interpret it?). If a positive test is found (and is a repeatable finding), then additional testing can be pursued to assess for underlying diseases. Further quantification can be done, if desired, using an ELISA for canine albumin but must be submitted to a reference laboratory. Progression to overt proteinuria can be monitored closely. Overt proteinuria is currently managed with a low protein diet and administration of an ACE inhibitor such as Enalapril. Addition of an anti-thrombotic such as aspirin may be used in advanced cases. Further information is required in order to determine at which point therapeutic intervention would be most beneficial, although theoretically early detection does allow for earlier intervention where appropriate.