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
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. 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.
Protein losing nephropathies (PLN) include glomerulonephritis (GN), glomerulopathy, and amyloidosis. The normal glomerulus
acts as a sieve to allow free filtration of small molecules, like urea, creatinine, sodium, water, etc. but restricts passage
of larger or negatively charged molecules. Molecules the size of albumin or larger do not pass through the glomerulus unless
damage has widened the pores or disrupted the charged surface. In glomerulonephritis, this damage is due to antigen-antibody
complexes that "clog" the pores and activate complement, causing an inflammatory reaction. Platelet activation further exacerbates
the damage to the glomerular capillary. Familial glomerulopathy is an inherited condition with abnormal glomerular collagen
deposition leading to proteinuria and progressive renal failure. In amyloidosis, abnormal amyloid protein is deposited in
the glomerulus. PLN may be fairly common in dogs, with cats having a lower incidence.