Pesky Proteinuria: When to Care About Protein in the Urine

Lisa Hann, DVM, DACVIM

We have all been in that situation when we get the results of a urinalysis, and there is protein in the urine that we were not expecting. The question is always: is it clinically important? There are many cases in which we are safe to “ignore” it, but other times missing it or ignoring it could be harmful for your patient.

Noting proteinuria can be important for two reasons. First, if there is significant renal proteinuria, appropriate evaluation is required to better define the type of renal proteinuria and appropriate therapy targeted at treating it. Second, proteinuria from another extra-renal cause may alert you to something happening elsewhere in the body that should be identified and treated if you were not aware of it already.

Causes of proteinuria

A persistent high level proteinuria is often indicative of chronic kidney disease or protein-losing nephropathy, but proteinuria can also be secondary to a variety of metabolic, neoplastic, inflammatory and infectious diseases. If persistent proteinuria is identified, it can trigger an appropriate diagnostic workup to identify the cause of the proteinuria. We also know that for renal disease, proteinuria left untreated can cause faster progression of disease and a higher level of complications including mortality, so it is important to quantify and monitor proteinuria in our chronic kidney disease patients. The American College of Veterinary Internal Medicine has identified persistent proteinuria in a consensus statement as three or more positive results 2 weeks apart.

One important disease that is sometimes forgotten in the process of evaluating proteinuria is Cushing’s disease. This disease can cause proteinuria by several mechanisms, and has been reported to cause a UPC of up to ~5.0. Mechanisms involved include hypertension with increased renal blood flow as well as glucocorticoids causing some degree of glomerular dysfunction. This proteinuria does not respond as well to generic renal proteinuria therapy unless the Cushing’s disease is also addressed, so it is important that if a dog is identified to have proteinuria and also has clinical signs and clinicopathologic changes consistent with Cushing’s disease, thorough diagnostic testing should be pursued along with appropriate therapy if Cushing’s is confirmed.

If I have a case that I am evaluating, and proteinuria has been reported on the urinalysis, there are several questions that I ask myself:

  • How was the sample obtained?
    • If proteinuria is noted on a voided sample, repeat urinalysis on a cystocentesis sample.
  • What is my specific gravity?
    • A positive protein urine result in a well concentrated urine indicates a smaller degree of protein loss than in a dilute urine, so attention should definitely be given to significant proteinuria in more dilute urine.
  • Do I have a reasonable explanation for the proteinuria that makes the proteinuria less concerning?
    • Obvious post-renal disease
    • Patient had a seizure or a fever
    • Intravascular IMHA or other disease causing excess blood protein levels
  • If there is not an obvious cause of the proteinuria, can I identify one with more thorough diagnostics?
    • Abdominal ultrasound, urine culture, assess blood proteins
  • Is the proteinuria persistent?
    • Unless you can explain why a patient has proteinuria, persistent proteinuria should be further quantified with a UPC and further investigation should be pursued.
  • Is there concurrent azotemia and/or hypoalbuminemia?
    • These patients may require additional and more aggressive therapy and management.
    • Depending on degree of derangement, these changes may dramatically affect prognosis, which should be explained to the patient’s family.

Here are some important reminders and guidelines for proteinuria:

1. Even low level renal proteinuria should be treated as this helps slow down disease progression. This may involve both drugs for proteinuria and treating concurrent hypertension. Start treatment when

  • Use a cystocentesis sample.

2. Even low level renal proteinuria should be treated as this helps slow down disease progression. This may involve both drugs for proteinuria and treating concurrent hypertension. Start treatment when

  • UPC ≥ 2.0 in nonazotemic dogs and cats
  • UPC ≥ 0.5 in azotemic dogs
  • UPC ≥ 0.4 in azotemic cats

3. Typical starting therapy for renal proteinuria may include a prescription renal diet and an ACE inhibitor such as enalapril or benazepril. Amlodipine is also used for more persistent and aggressive hypertension.

Many cases of proteinuria are easily solved and managed, but some are complicated, and others are refractory to routine therapy. It can be very appropriate to consult with an internist or criticalist or consider a full referral for further evaluation of your patient, if help is needed. Feel free to give our internal medicine service a call should you need to consult on a case.

Ettinger and Feldman. Textbook of Veterinary Internal Medicine 7th Ed. Saunders, Elsevier Inc., 2010. Vol 1, 168-171.