CVC Central 2007 Highlights: Investigating proteinuric kidney disease

Do you sometimes detect protein in a sick patient's urine or even on routine testing in a seemingly healthy patient and you're not sure what to make of it? If red blood cells or inflammatory cells are not present, the proteinuria could be important. But first, retest the patient's urine a week or two later to see if the results are repeatable. If not, the previous proteinuria may have been caused by a one-time event, such as stress, fever, or vigorous exercise.

Also consider that one cause of false positive urine protein results on a dipstick test is alkaline urine. And a false positive result may occur with a turbidometric test performed by a diagnostic laboratory if a patient has recently received penicillins, cephalosporins, sulfonamides, or radiographic contrast agents.

If the second sample shows proteinuria, perform a urine protein/creatinine ratio to determine the extent of protein loss in the urine.

ASSESSING URINE PROTEIN/CREATININE RATIOS

Urine protein/creatinine ratios < 0.2 in dogs and cats indicate normal urine protein loss, while those between 0.2 and 0.5 in dogs and 0.2 and 0.4 in cats indicate borderline proteinuria and necessitate assessing the patient's kidney function. If the results are normal, recheck the urine in a few months.

Urine protein/creatinine ratios that are > 0.5 in dogs and > 0.4 in cats necessitate a more thorough work-up. Ratios > 3 may indicate glomerular disease. With lower abnormal ratios, also consider nonglomerular pathology, such as hypertension, hyper adrenocorticism, or renal tubule defects.

Nonazotemic patients with ratios > 2, azotemic dogs with ratios > 0.5, and azotemic cats with ratios > 0.4 warrant treatment. In patients with substantial proteinuria, hypoalbuminemia may occur.

FURTHER EVALUATION

If a more thorough work-up is indicated, perform a serum chemistry profile to evaluate albumin, blood urea nitrogen, creatinine, and cholesterol concentrations and liver enzyme activities and a complete blood count to detect any abnormalities consistent with an infectious or inflammatory process. Additional blood testing may be needed to rule out heartworm disease, tick-borne illnesses, and hyperadrenocorticism.

Urine bacterial culture and sensitivity testing are also warranted, especially in patients with dilute urine concentrations. Test cats for feline leukemia virus and feline immunodeficiency virus infections if their status is unknown. Since hypertension can be closely associated with proteinuria and many of the diseases that cause it, be sure to obtain serial blood pressure measurements. Thoracic and abdominal radiographic or ultrasonographic examinations may also yield important information. Obtaining kidney biopsy samples may be helpful in some patients. And certain breeds may be predisposed to familial kidney diseases, so it's important to research this possibility as well.

THERAPEUTIC MEASURES

Over time, marked proteinuria can lead to severe hypoalbuminemia and edema, hypercoagulopathy, and progressive kidney disease. High levels of proteinuria can be directly nephrotoxic—so it's important to treat these patients. Switching to a renal diet may reduce albumin loss in the urine but should not reduce the serum albumin concentration. So be sure to monitor serum albumin concentrations and the patient's weight and muscle and coat condition.

Angiotensin-converting enzyme inhibitors play a major role in treating proteinuria. A 50% reduction in urine protein/creatinine ratios indicates improvement. Patients must be monitored carefully to ensure that kidney function does not worsen while they are receiving these medications.

Patients with hypertension may require additional treatment. The anticoagulant and antiplatelet effects of low-dose aspirin can also be beneficial in preventing thrombotic events. And, of course, if during your work-up an underlying infectious or noninfectious condition is found to be causing immune-mediated mechanisms leading to kidney damage, direct your therapies toward eliminating that condition, if possible. Although of unproven value in managing proteinuria in dogs and cats, omega-3 fatty acid supplementation may be considered to reduce intraglomerular pressure and inflammation.

A FINDING NOT TO BE IGNORED

If, in the past, you've been inclined to not worry about proteinuria in a seemingly normal patient, it's time to start paying attention. In patients with chronic kidney disease, the risk of an adverse outcome worsens 1.5 times for every increase by 1 in a patient's urine protein/creatinine ratio.1,2 Your clients will appreciate your proactive approach to their pets' care.

Editors' note: Dr. Polzin has received research sponsorship and speaking honoraria from Hill's Pet Nutrition, Royal Canin, and Nestlé Purina; receives support for the International Renal Interest Society from Novartis; and has consulted for and received honoraria from Bayer, Pfizer, and Vétoquinol.

David J. Polzin, DVM, PhD, DACVIM (small animal internal medicine), Department of Veterinary Clinical Sciences,College of Veterinary Medicine, The University of Minnesota, St. Paul, MN 55108.

REFERENCES

1. Jacob F, Polzin DJ, Osborne CA, et al. Evaluation of the association between initial proteinuria and morbidity rate or death in dogs with naturally occurring chronic renal failure. J Am Vet Med Assoc 2005;226:393-400.

2. Syme HM, Markwell PJ, Pfeiffer D, et al. Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria. J Vet Intern Med 2006;20:528-535.