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Hypoalbuminemia

What to do with a Hypoalbuminemic Patient
Brianna Backlund, DVM, DACVIM

Albumin is the major determinant of the oncotic pressure of the vascular system. Due to its size, albumin can’t passively cross the endothelial membrane, so it stays within the vascular space and helps holds fluid within the vessels. When albumin levels get low, the oncotic force is lost and fluid leaks out of the vascular space.

The clinical signs most often seen with hypoalbuminemia relate to effusions or thromboembolic disease and are related to the severity of the hypoalbuminemia. Albumin levels of 1.5mg/dL or less are often associated with development of edema, effusions and/or thromboembolic disease. Thrombosis occurs because the anticoagulant protein, antithrombin, is the same size as albumin and is lost in those conditions where albumin is also lost. If body cavity effusion is noted, it is first important to sample this fluid to ensure that it is consistent with a pure transudate (TS < 2 g/dl) that we expect to see in association with hypoalbuminemia.

There are four main causes of hypoalbuminemia: hepatic failure, protein-losing nephropathy (PLN), protein-losing enteropathy (PLE) and vasculitis due to inflammation or sepsis. Initial diagnostics should start with a CBC, chemistry and urinalysis.

Hepatic failure

With hepatic failure, liver enzymes may be elevated but can be normal in end-stage disease. Low glucose, low cholesterol and low BUN can be markers of failure. If bilirubin is still within the reference range, the next reasonable step is to perform fasted and fed bile acids and or resting ammonia. Bile acids are not warranted if the bilirubin is elevated. The differential list for patients with hepatic failure include:

  • Inflammatory hepatitis
  • Infectious hepatitis
  • Copper toxicity
  • Hepatic fibrosis
  • Idiopathic hepatic lipidosis
  • Hepatic neoplasia
  • Portosystemic shunt (PSS)
  • Feline infectious peritonitis (FIP)

Although the list is relatively short, it does consistently touch on many different pathologies, so liver sampling is indicated to best diagnose the underlying process. Coagulation times should always be evaluated prior to sampling to minimize the risk of hemorrhage during biopsy. The size and quality of the liver sample greatly influences how diagnostic the sample is. An ultrasound guided fine needle aspirate for cytology is helpful for diagnosing round cell tumors, and an argument can be made for its use in the diagnosis of idiopathic hepatic lipidosis. For all other conditions, liver biopsy is the most relied upon diagnostic for defining the underlying liver process. A biopsy is best indicated to help make recommendations for therapeutics as there is a long list of medications used for the various hepatic disorders ranging from steroids, antibiotics, chemotherapeutics, copper chelators, etc.

Protein-losing nephropathy

If there is evidence of urine protein loss, the next easiest step is to perform a urine protein:creatinine ratio as an easy rule in/out. If the UP:C is not significant or is borderline, then it is unlikely the cause for the hypoalbuminemia. The most common causes of PLN include amyloidosis, glomerulonephritis and glucocorticoid excess, either endogenous or exogenous. Although a renal biopsy is indicated to determine the underlying process, due to the invasive nature of the renal biopsy, this is seldom pursued. Screening for Lyme disease should always be performed if a PLN is diagnosed.

Protein-losing enteropathy

Protein-losing enteropathy is suspected when there is no protein in the urine, the liver enzymes are normal and the globulin levels are low. The most definitive diagnostic for GI albumin loss is a fecal alpha-1 proteinase inhibitor evaluation on fecal samples, which has only been demonstrated to be reliable in adult dogs. The test is a mean value on three fecal samples submitted with special handling to the GI lab at TAMU. The results are slightly delayed in turnaround, so the test seems to be mostly academic and seldom performed. Usually, we evaluate bile acids as well as UA or UP:C and incriminate the GI tract by either clinical impression or diagnosis of exclusion. The most common causes of PLE include: IBD, lymphangiectasia, fungal pathogens (histoplasmosis or pythiosis) or GI parasitism. Because therapies are very different for each of the pathologic processes, intestinal biopsies are recommended – most often in the form of endoscopic biopsies to minimize healing complications. It is also recommended to evaluate cobalamin levels to determine if supplementation is indicated as well as to guide sampling localization – if upper or upper/lower endoscopic sampling is indicated.

Vasculitis

Pets with vasculitis are often quite sick and may have fever, abnormalities in white blood cell count or evidence of toxic change. Treatment involves finding the cause of the inflammation or sepsis and directly managing the precipitating condition.

Regardless of the cause of hypoalbuminemia, resolving the condition requires therapies tailored to the underlying process. Supportive therapies include addressing effusions as well as prevention of thromboembolic disease. Centesis for removal of offending effusions can be diagnostic as well as therapeutic. Due to the risk of thromboembolic disease, once diagnostic samples have been obtained, it is recommended to start clot preventative therapies – aspirin at 0.5mg/kg/day or clopidogrel at 1-3mg/kg/day are most commonly recommended until albumin levels have returned to within the normal range suggesting that the concurrent loss of antithrombin is reduced and the peak risk for thromboembolic disease is passed.

Nutrition is also a key part in resolving hypoalbuminemia. Albumin synthesis decreases in the face of negative caloric balance, so positive caloric intake helps with increased production of this protein.

The internal medicine service is always available to help with hypoalbuminenia or other difficult cases. We are happy to answer questions over the phone and can help with referrals Monday – Saturday in both Seattle and Renton.