Glomerular disease is a broad term used to describe a number of renal diseases that can lead to renal failure and death. Damage to the glomerulus increases capillary permeability to proteins such as albumin, resulting in the presence of proteins in urine (referred to as proteinuria).
In humans, proteinuria can result from a number of diseases, including diabetes, hypertension and IgA nephropathy. The conventional test for proteinuria in humans is to use a standard protein dipstick assay as described, for example, in Bakris, Curr. Opin. in Neph. and Hypertension, 5:219–223 (1996). Dipsticks that are chemically impregnated with sulfosalicylic acid to measure proteins in a sample are commercially available, for example from Boehringer-Mannheim, Germany (Chemstrips™) and Ames Colo., USA (Albustix™). One drawback to these dipstick assays is that they require a significant amount of protein in the urine to be detected. Amounts of protein in humans of less than 300 milligrams per day are not detectable by the dipstick assay, yet proteinuria may still be present. Another drawback to these protein-based assays is that they are incapable of discriminating between different types of protein (e.g., albumin, globulin, etc.) that may be present in urine. Proteinuria may result from the leakage of serum proteins into glomerular filtrate due to glomerulernephritis; however, proteinuria may also be present due to problems unrelated to renal disease such as bladder infections or a high-protein diet.
Lower amounts of albumin in the urine, referred to as “microalbuminuria,” indicate a level of albumin that is greater than in normal patients, but lower than in patients with overt proteinuria, i.e., clinically proteinuric. In humans, microalbuminuria refers to amounts of albumin between 30 milligrams per day and 300 milligrams per day according to Watts, Clin. Chem., 32(8): 1544–1548 (1986). Methods to detect human microalbuminuria are known and include those methods that use an anti-human albumin antibody to detect amounts of human albumin that are not detectable by known dipstick methods. Such methods of detecting human microalbuminuria are described, for example, in U.S. Pat. No. 5,246,835, issued on Sep. 21, 1993, to Suzuki et al.
Although microalbuminuria can be detected in humans, the utility of detecting microalbuminuria in humans may be very limited, at least according to some reports. For example, using the microalbuminuria tests to predict renal disease has only been recommended for humans with diabetes according to Bakris, supra. Because disorders other than diabetes, such as hypertension, heart disease and IgA nephropathy do not lead to consistent microalbuminuria in humans, according to Bakris, supra, detecting microalbuminuria has poor predictive value for later renal disease associated with these non-diabetic disorders states. Accordingly, using microalbuminuria tests to screen for potential or early renal disease in non-diabetic human patients is generally not recommended by Bakris, supra.
Renal disease is also a significant health problem in companion animals, particularly dogs and cats. In dogs, the primary cause of renal disease is damage to the glomerulus in the kidney. Although glomerular damage in dogs can occur in any number of ways, it is most commonly caused when circulating immune complexes (i.e., antibody/antigen complexes) are deposited in the glomerular capillaries as a result of systemic illness as described in Batamuzi, et al., Vet Record, 143; 16–20 (1988). Several diseases have been implicated in the pathogenesis of immune complex formation, including for example, dirofilariasis and other parasitic infections, diabetes, hypothyroidism and others.
Early renal disease in veterinary medicine has been characterized by glomerular changes detectable by histopathology, including the use of light microscopy or occasionally immunofluorescence as reported in Vaden, Proc. 17th ACVIM, 420 (1999). However, as reported in that paper, these techniques can lead to misdiagnosis of the cause of the renal disease. Determining the cause of the renal disease is useful in formulating an appropriate treatment regimen. For example, if the cause of the renal disease is immune-mediated, then immunosuppressive therapy may be appropriate. However, currently available assays to detect human microalbuminuria are not sufficiently sensitive to detect canine microalbuminuria.
Thus, a need exists for assays to detect canine early renal disease in companion animals. The present invention satisfies this need and provides related advantages as well.
USPTO Backgrounds
USPTO Backgrounds