Urine proteins consist in a variable quantities of proteins that originate from plasma, urinary tract, genital tract and method of collection. The term "proteinuria" is used to define an abnormal quantity of proteins in urine that exceed 20mg per kilo of body weight per day. The anatomy and physiology of renal glomeruli, in normal conditions, do not allow proteins that have molecular weight higher than 68,000 Daltons (albumin) to be eliminated in the urine. Peptides (including several hormones) appear in glomerular ultrafiltrate, but are normally reabsorbed by proximal renal tubules. Abnormal proteinuria is usually classified as preglomerular, glomerular and postglomerular.

Preglomerular proteinuria depends from damages that do not involve the urogenital tract and may be functional or due to overload. Functional proteinuria may be associated with strenuous exercise, extreme hot or cold, stress, fever, seizures. Overload proteinuria may be tubular (if associated with excessive production of low molecular weight plasma proteins) or glomerular in case of excessive production or administration.

Glomerular proteinuria develops as a consequence of alteration of glomerular capillary barriers that prevent loss of larger plasma proteins into ultrafiltrate; it is the most commonly recognized form of proteinuria and is commonly associated with numerous infectious diseases in both dogs and cats.

Postglomerular proteinuria comes from defects in proximal tubules absorption; also genital tracts may influence presence of proteins in urine as well as inflammation, neoplasia or trauma affecting lower urinary tracts.

Bence Jones proteinuria is the presence of proteins that precipitate when the urine is gradually warmed (45 to 70°C) and then redissolve as urine is further heated. Bence Jones proteins are observed in urine of patients with multiple myeloma.

Urine proteins may be detected with qualitative, semiquantitative and quantitative methods. In routine urinalyses, usually dipstick colorimetric test is the most commonly used; it is a semiquantitative test. Specific gravity is an important value to be considered, since mild proteinuria in presence of a low SG means a greater loss of proteins than in case of higher value of SG. It is always very important to interpret test results on proteinuria in association with other clinical and laboratory findings. Twenty-four hour urine collection is the traditional and best accepted method of determining urine protein content, however this method is time consuming, needs a metabolism cage if persistent catheterisation is not used, and catheterisation itself places the patient at risk for urinary tract infection. Urine protein-creatinine ratios (U-P/Cr) are actually routinely accepted as accurate methods to evaluate normal or abnormal urine protein content.

A random urine sample is collected and the protein and creatinine concentration are measured in milligrams per decilitre; subsequently the ratio is calculated, dividing the creatinine value into the protein value. Usually if the ratio is greater than 1, it is considered abnormal.

Massive proteinuria associated with hypoalbuminemia (less than 2g/dl) can lead to the appearance of oedema and ascites. The nephrotic syndrome is defined as marked proteinuria, oedema, hypoalbuminemia and hypercholesterolemia. Renal amyloidosis, common in some breeds of dogs (e.g., Shar pei) and cats (e.g., Abyssinian) is cause of abundant proteinuria with a very high U-P/Cr.

Antithrombin III is a globulin with a molecular weight of approximately 65,000 dalton and it is lost in the urine of animals with glomerular damage. Dogs with less than 70% of normal antithrombin III activity are in danger of developing hypercoagulation with pulmonary and systemic thromboses.

The diagnostic approach to proteinuric dogs and cats needs an accurate evaluation of the history and physical examination; the problem must be localized as accurately as possible; signs of systemic diseases are usually associated with renal disorders; chronic inflammation may lead to glomerular disease. The physical examination should consider abdominal palpation to evaluate the kidney and the bladder, rectal examination to evaluate the prostate. Control of the retina by ophthalmoscopic examination may show alteration in the retinal vasculature, retinal hemorrhage or detachment, signs of systemic hypertension. Indirect measurement with Doppler or Oscillometric devices are also very useful for routine monitoring of the blood pressure. Diagnostic imaging, performed with contrast abdominal radiographs, abdominal ultrasonography or renal biopsy may be very important for the correct interpretation of the cause of proteinuria.

Treatment of proteinuria should be primarily directed against the origin of the disease causing the glomerular damage; further steps should be directed to control, if possible, the mechanisms that are at the base of the glomerular damage development. Up to now does not appear yet solved the problem concerning the usefulness of immunosuppressive drugs to reduce deposition of immunocomplexes in the glomerular structure. Cyclosporin was found to be of not benefit in reducing proteinuria with idiopathic GN in dogs; treatment with corticosteroids appear to be detrimental, leading to azotemia and worsening of proteinuria. Corticoids would be indicated however in case of diseases steroid responsive (e.g., systemic lupus erythematosus).

Platelets and thromboxane have an important role in the pathogenesis of GN, therefore dietary supplementation with omega-3 fatty acids can significantly reduce thromboxane synthesis in stimulated platelets and glomerular cells. To decrease the risk of platelet aggregation (thrombi formation), an extreme low dosage of aspirin (0.5mg/kg SID) may selectively inhibit platelet cyclooxygenase without preventing the beneficial effects of prostacyclin formation.

ACEI reduces protein excretion in human and animals with GN, reduces the intraglomerular hypertension, by dilating the efferent arteriole, and slows glomerular mesangial cells growth and proliferation that can alter the permeability of the glomerular capillary wall and lead to glomerulosclerosis.

References

1.  Grauer, G.F., DiBartola S.P., Glomerular disease. Textbook of Veterinary Internal Medicine, S.J.Ettinger, E.C.Eldman, fifth edition, W.B Saunders,1662-1676, 2000.

2.  Lulich J.P., OsborneC.A. Interpretation of urine protein creatinine ratio in dogs with glomerular and non-glomerular disorders. Compend Contin Ed Prac Vet 12:59, 1990

3.  Grauer G.F., Update on the Management of Canine Glomerular Disease. Recent Advances in Canine and Feline Nutrition. Volume II, 2000 Iams Nutrition Symposium Proceedings 375-382, 2000

4.  Brown A.S., Primary Diseases of Glomeruli. Canine and Feline Nephrology and Urology, C.A.Osborne, D.R.Finco, Lea & Febiger, 368-385, 1995.