Gregory F. Grauer, DVM, MS,
Diplomate, ACVIM (Internal Medicine)
Professor and Section Chief Small Animal Medicine
Department of Clinical Sciences, VTH
Colorado State University
300 West Drake Road
Fort Collins, CO 80523
ggrauer@vth.colostate.edu
2001
How is proteinuria detected?
Proteinuria is routinely detected by the dipstick colorimetric test. This test is inexpensive and easy to use; amino groups of proteins bind to the indicator incorporated in the filter paper on the dipstick and cause a color change. The color change is graded by comparison to a standard, but the comparison is subjective. The dipstick test is most sensitive to albumin inasmuch as albumin has more free amino groups compared with globulins or Bence-Jones proteins. False-positive results may be obtained with alkaline urine, urine that has been contaminated with quaternary ammonium compounds, or if the dipstick is left in contact with the urine long enough to leach out the citrate buffer that is incorporated in the filter paper pad. False-negative results may occur with Bence-Jones proteinuria or dilute or acidic urine. The sensitivity of the dipstick test is approximately 30 to 1000 mg/dl. The dipstick method is not affected by urine turbidity; however, the supernatant from centrifuged urine samples should be used for analysis.
What is the cause of my patient's proteinuria?
When presented with a cat or dog with proteinuria, it is important to identify its source. Proteinuria may be caused by physiologic or pathologic conditions. Physiologic or benign proteinuria is often transient and abates when the underlying cause is corrected. Strenuous exercise, seizures, fever, exposure to extreme heat or cold, and stress are examples of conditions that may cause physiologic proteinuria.
Pathologic proteinuria may be caused by urinary and nonurinary abnormalities. Nonurinary disorders associated with proteinuria often involve the production of small-molecular-weight proteins
that are filtered by the glomerulus and subsequently
overwhelm the resorptive capacity of the proximal tubule. Examples of this include production of immunoglobulin light chains (Bence-Jones proteins) by neoplastic plasma cells, and release of hemoglobin from damaged red blood cells,
which exceeds the binding capacity of haptoglobin.
Pathologic urinary proteinuria may arise from renal or nonrenal sources. Nonrenal proteinuria is most frequently associated with lower urinary tract inflammation or hemorrhage. Changes in the urine sediment usually reflect the underlying cause (e.g., urolithiasis, neoplasia, trauma, or bacterial cystitis). On the other hand, renal proteinuria is most often caused by glomerular lesions. Glomerulonephritis and amyloidosis alter the selective permeability of the glomerular capillaries and frequently result in proteinuria greater than 50 mg/kg/24h or urine
protein/creatinine ratios greater than 3.0. Persistent
proteinuria with a normal urine sediment or accompanied by hyaline cast formation is strongly suggestive of glomerular disease.
How do you interpret a positive protein reaction on the urine dipstick?
Proteinuria detected by the urine dipstick should always be interpreted in light of urine specific gravity and urine sediment. Significant proteinuria may be overlooked if urine is dilute and voluminous. Conversely, a protein reaction of trace or 1+ may be normal in concentrated urine. For example, a 2+ proteinuria with a 1.010 urine specific gravity suggests much greater urine protein loss on a 24-hour basis than does a 2+ proteinuria with a 1.040 urine specific gravity. In addition, urine protein concentration is frequently increased in patients with lower urinary tract inflammation and/or hemorrhage. Therefore proteinuria should also be assessed in relation to urine sediment changes that are compatible with inflammation or hemorrhage (e.g., bacteria and increased numbers of white and red blood cells and epithelial cells in the urine sediment). Prerenal (physiologic and pathologic-nonurinary) and postrenal (pathologic urinary-nonrenal), as well as inflammatory renal proteinuria, can usually be identified on the basis of history, physical examination, and urine sediment changes. Renal proteinuria caused by abnormal tubular resorption is frequently accompanied by glucosuria and abnormal urinary loss of electrolytes, which helps differentiate tubular from glomerular proteinuria. Identification of the source of the proteinuria is important, since quantitation of glomerular proteinuria can be a helpful prognostic tool, although it is not useful in patients with prerenal or postrenal proteinuria.
When should you quantitate proteinuria?
If the dipstick method or the sulfosalicylic acid test for proteinuria suggest significant proteinuria in light of the urine specific gravity and the urine sediment examination is normal (i.e., suspected renal proteinuria), urine protein excretion should be quantitated. Quantitation of renal proteinuria helps to evaluate the severity of renal lesions and to assess response to treatment or progression of disease.
Calculation of the urine protein/creatinine ratio from canine and feline urine samples has been shown to accurately reflect the quantity of protein excreted in the urine over a 24-hour period. A complete urinalysis should always be obtained before or along with the urine protein:creatinine ratio, since hematuria or pyuria may indicate significant nonglomerular proteinuria. If there is evidence of inflammation (e.g., pyuria, bacteriuria), the protein determination should be repeated after successful treatment of the inflammatory disorder. The urine protein/creatinine ratio cannot be used to differentiate glomerular proteinuria from proteinuria associated with lower urinary tract inflammation or hemorrhage.
How do you diagnose glomerulonephritis?
Persistent, severe proteinuria with a normal urine sediment (hyaline casts may be observed) is the hallmark clinicopathologic abnormality associated with glomerulonephritis. The urine protein/creatinine ratio is used to quantitate the magnitude of the urine protein loss. Definitive diagnosis of protein-losing nephropathies is made by evaluation of renal cortical histopathology.
