Proteinuria and protein losing nephropathy (Proceedings)

Nov 01, 2009


Proteinuria can be pre-glomerular, glomerular, or post-glomerular in origin. Pathologic proteinuria is a persistent problem from glomerular damage, whereas functional proteinuria is generally transient. Infection or inflammation (including neoplasia) of the lower urinary tract can induce significant proteinuria, and urinary protein should always be evaluated in light of the urinary sediment and culture results and the clinical signs present. Non-glomerular renal diseases, such as pyelonephritis, severe chronic renal failure, or acute tubular necrosis may also cause proteinuria. Excessive protein delivery to the kidney ("pre-glomerular proteinuria") may lead to proteinuria, in conditions such as hemoglobinuria or multiple myeloma. Transient damage to the glomerulus from fever or heatstroke may cause transient proteinuria, but exercise does not appear to cause proteinuria in dogs as it does in people. The interval to determine whether proteinuria is persistent is not firmly established, but rechecking a month later seems clinically reasonable.

There are 4 tests in widespread use for detecting proteinuria. The urine dipstick is a semi-quantitative test that is a good screening test, but has many false positive results. Highly concentrated urine, alkaline urine, and feline urine are more likely to have false positive results. Any positive dipstick result should be confirmed with sulfosalicylic acid (SSA) turbidometric testing, which is a highly specific test.

Microalbuminuria tests for both dogs and cats are available. Microalbuminuria is defined as small amounts of albumin in the urine (1-30 mg/dl), a level that would not be detected by standard testing such as the urine dipstick or SSA test. The lower limit of the urine dipstick is urinary albumin 30 mg/dL. Detection of persistent or progressive microalbuminuria should prompt a careful search for infectious, inflammatory, metabolic, or neoplastic conditions that are causing secondary renal damage.

Microalbuminuria testing is not necessary for animals with overt proteinuria. Microalbuminuria can be used as an early screening test in apparently healthy animals with a predisposition to renal disease, such as age, breed-associated predisposition to glomerular disease, or diseases associated with glomerular damage. A low positive test that is stable should be monitored; a high positive test or progressive increase in the level of microalbuminuria should prompt action (i.e., intensified diagnostic testing).

Quantification of the amount of protein using a protein:creatinine ratio (UPC) is warranted with a positive screening test, unless an obvious cause of proteinuria is present (i.e., hematuria, active urine sediment, positive culture). In healthy dogs, the UPC is less than 0.5. Values over 1 are considered abnormal. Values between 0.5 and 1 are questionable, and should be monitored for persistence or worsening. In cats with chronic kidney disease, a UPC over 0.4 is associated with shorter survival, and values over 0.2 should be considered potentially abnormal. Because of the day-to-day variability in UPC, measuring UPC in urine samples collected on separate days is ideal. Equal volumes of these urine samples can be pooled to decrease the expense of repeated testing. In dogs, one UPC measurement is adequate to reliably estimate UPC when < 4. When monitoring changes in UPC over time, a change of 80% is needed to demonstrate a significant difference when the UPC is around 0.5, but only a 30% change is needed when the UPC is higher (around 12).

A consensus statement (Lees G, et al. JVIM 2005;19(3):377-385) recommends monitoring, investigating, or intervening depending on the level of proteinuria and the presence or absence of azotemia. In nonazotemic dogs and cats, microalbuminuria or a UPC > 0.5 prompts monitoring, a UPC > 1 prompts investigation, and a UPC > 2 prompts intervention. In azotemic dogs, intervention is recommended at a UPC > 0.5, whereas intervention is recommended at a UPC > 0.4 in azotemic cats.