The protein-creatinine ratio on random mid-day urine samples correlates well with the cumbersome "gold standard" (no pun intended), the 24-hour urine collection, for quantitating urinary protein loss. It is unaffected by urine volume or concentration. Determination of the urine protein-creatinine ratio assumes the following:
- Stable GFR
- Constant protein loss
- Constant glomerular filtration
- Tubular function affects proteins and creatinine similarly. In reality, tubular secretion of creatinine increases as plasma creatinine concentration increases, therefore the ratio may be decreased in azotemia.
Factors affecting urine protein-creatinine ratios
- Guidelines from ACVIM consensus statement (Lees et al 2005, J Vet Intern Med; 19:377):
- Dogs: In healthy dogs, the urine protein to creatinine ratio (UP:UC) is usually < 0.5. Values ≥ 0.4 in azotemic dogs are abnormal. Values between 0.5-1.0 in non-azotemic dogs are considered equivocal and continued monitoring for progression is recommended. Values >1.0 in non-azotemic dogs are abnormal and diagnostic evaluation is warranted. Glomerular proteinuria is usually associated with UP:UC ≥ 2.0. Therapeutic intervention is recommended for azotemic dogs with UP:UC ≥ 0.5. These figures are only valid for urine samples with inactive sediments.
- Cats: In healthy cats, the urine protein to creatinine ratio (UP:UC) is usually < 0.5. Values ≥ 0.4 in azotemic cats are abnormal. Values between 0.5-1.0 in non-azotemic cats are considered equivocal and continued monitoring for progression is recommended. Note that some healthy male cats can have UP:UC values within this range (up to 0.6). Values >1.0 in non-azotemic cats are abnormal and diagnostic evaluation is warranted. Glomerular proteinuria is usually associated with UP:UC ≥ 2.0. Therapeutic intervention is recommended for azotemic cats with UP:UC ≥ 0.4. These figures are only valid for urine samples with inactive sediments.
- Mild increases: Can be seen in prerenal or renal proteinuria or proteinuria that accompanies genitourinary hemorrhage or inflammation.
Tubular proteinuria usually results in protein-creatinine ratios of
< 2.0 (range: 1.0-5.0).
- Moderate to severe increases: Urine protein-creatinine ratios
> 2.0 (usually > 5.0) are seen with glomerular disease, e.g. glomerulonephritis or amyloidosis. The severity of proteinuria does not distinguish between causes of glomerular disease.
- Hemorrhage: The protein-creatinine ratio will increase proportionally
to the degree of blood in the urine (due to the contribution of serum protein that comes along with the blood). Heavy blood contamination with accompanying plasma protein frequently
invalidates the ratio. Mild blood contamination from cystocentesis (i.e. 5-20 RBC/HPF
or even > 100 RBC/HPF) does not usually cause a proteinuria (on the dipstick or with urine protein to creatinine ratios).
- Infection: The protein-creatinine ratio is invalid in the presence of a urinary tract infection. Ratios as high as 40 can be seen with E. coli infections. The ratio does not correlate to the number of red or white cells/HPF in these cases. Some cases of urinary tract infections can have normal protein to creatinine ratios so the degree of proteinuria in these cases cannot be predicted from the degree of cystitis. Proteinuria with infection is attributed to leakage of serum protein due to inflammatory-induced changes in vascular permeability which may depend on the severity and nature of the inflammation.
- Inflammation: Inflammation, without infection, will increase the urine protein-creatinine ratio, but usually the ratio is < 2.0.
Therefore, urine protein-creatinine ratios should not be measured in animals with "active" urine sediments.
- Drugs: Immunosuppressive doses of corticosteroids (2 mg/kg q 12 h for 6 weeks) will increase the urine protein-creatinine ratio mildly (up to 1.3). This is attributed to mesangial cell proliferation.
© Cornell University