Protein Losing Diseases

The following Zoom webinar is produced by the SCWT Club of America and also SCWTCA Endowment Inc. (Zoom is not needed to view). This webinar is on the topics of PLN & Kidney Disease update Click here (opens on a new page)


Your dog’s body produces a number of extremely important proteins, called enzymes. One group of these are the digestive enzymes that participate in the breakdown and digestion of food.

In humans, digestion begins in the mouth where saliva contains digestive enzymes. Dogs, however, don’t chew their food they gulp it down in chunks. Dog saliva serves in digestion only to moisten and lubricate the mouth and food as it is pushed back into the oesophagus for its journey to the stomach.

The gastro intestinal tract has to perform many functions in order to absorb food then excrete the waste products. The mucosal layer lines the inner surface of the tube and is responsible for secretion and absorption of nutrients to the body. The surface area of the mucosa contains villi. Damage to the villi can cause villous atrophy which leads to malabsorption and diarrhoea.

The major digestive and absorption processes occur in the small intestine. Several digestive enzymes are mixed into the food along with bile. These secretions are used to break down carbohydrates, proteins and fats into smaller molecules, which are then absorbed by special cells while the mixture is churned and pushed along by intestinal muscle contractions.

Dogs intestines are relatively short (about five times their body length) so complex foods have a short time to be broken down and absorbed.

By the time this mixture reaches the large intestine, the final leg of its journey, there should be little of nutritional value left. The large intestine completes the absorption of water and electrolytes and the remaining undigested food is then filtered and stored for elimination in the colon.

When a dog suffers from malabsorption, as in the case of PLE, digestive enzymes fail to absorb protein into the body and it passes through the large intestine into the faeces. A forerunner to PLE can be inflammatory bowel disease (IBD).

PLE is characterised as a loss of protein from the intestines due to intestinal disease. There can be many causes of PLE, but it's important to note that there maybe a hereditary component in Wheatens, predisposing them to IBD and/or intestinal Lymphangiectasia.

  • PLE is a condition in which protein is lost excessively into the intestine and can represent a number of abnormalities, which result in the loss of plasma proteins from the gastrointestinal tract.

  • The loss of the healthy mucosal layer allows the leakage of vital protein-rich fluids. This is a hallmark of Protein Losing Enteropathy (PLE).

  • The liver and other cleansing systems are unable to compensate for the loss.

  • Mechanisms for gastrointestinal protein loss include lymphatic obstruction, mucosal disease with erosions, or ulcerations.

  • PLE is probably related to immunological defence of the intestinal tract.

  • The average age of onset is 4.5 years (range 0.5 to 11 years ).

  • A PLE dog may exhibit diarrhoea, vomiting, edema/ascites, picky appetite and weght loss. Since these are symptoms of many types of illness, serious and minor, proper diagnosis is important. Left untreated, PLE can become serious and fatal.

  • Treatment is with medication and diet and can result in extended life.

  • Tests necessary to detect the presence of PLE are blood, urine and, if necessary, endoscope biopsy and Faecal investigation.

  • Please refer to the Comparison Chart of Hereditary Diseases for signs and symptoms of this disease.

  • Learn more about PLE here

  • Learn more about IBD here

Please note that links given to articles that are general in nature on external websites are not a substitute for your own Veterinarian's advice.

The Testing Protocols page has information about tests available for PLE.

The mode of inheritance for PLE is not known.

At the present time there is no test available to show if dogs are carrying the deleterious (bad) mutations which cause this disease.

Care of Dogs with PLE - - article from DVM360

Canine chronic enteropathy - Current state-of-the-art and emerging concepts. From Frontiers of Veterinary Science. link here

For one owner's account of dealing with PLE, go to the link 'Megan - My Angel Eyes'



Kidney Anatomy:

The kidneys filter waste and extra fluid from the blood. The filtering process takes place in the nephron where microscopic blood vessel filters called glomeruli, are attached to fluid-collecting tubules. A number of different disease processes can damage the glomeruli, thereby causing kidney failure.


Glomerulonephritis and glomerulosclerosis are broad terms that include many forms of damage to the glomeruli.

PLN is also known as glomerular disease. It causes protein loss through the glomerulus, a structure of the kidneys.

While PLN can have several causes, it's important to note that Wheatens can have familial PLN due to podocytopathy causing glomerulosclerosis. Note that PLN is not "old age" kidney disease and is different to Renal Dyspasia. PLN can be associated with systemic hypertension, thromboembolic events, edema/ascites and eventually chronic renal failure.

Some forms of kidney failure can be slowed down but scarred glomeruli can never be repaired. This is what makes early detection so vital. Treatment given in the early stages of kidney failure depends on the disease causing the damage.

Kidney failure may be ‘silent’ for many years. Approximately 70% of the kidney can be damaged before any physical signs show themselves.


The glomeruli are the filters of the kidneys (imagine a water filter in a jug), they filter the blood and make urine. Normally, large molecules such as proteins, and cells such as red blood cells or white blood cells, do not pass through the filters and are retained within the blood because they are so important for health.

Small molecules pass completely through the filters. Some of these are completely reabsorbed back into the blood since they are so important in maintaining the right chemical balance of the body e.g. glucose, salt etc. Other molecules, which are not required for body functions are passed freely into the urine, for example Urea, Uric Acid and Creatinine.

There are two main effects of damage to the glomeruli. Substances, which are normally retained in the circulation escape into the urine through the filtration mechanism, one of these is Albumin. As a consequence, protein and red cells appear in the urine and can be detected by a dipstick urine test.

Protein in the urine is called proteinuria. Normally there is very little protein in the urine. If the damage gets worse, the filter shuts down and that function of the kidney is lost. If sufficient damage occurs to enough glomeruli kidney failure may occur.


Glomerulonephritis is the inflammation of the membrane tissue in the kidney that serves as a filter, separating wastes and extra fluid from the blood. Glomerulosclerosis describes the scarring or hardening of the tiny blood vessels within the kidney.  

Protein Losing Nephropathy (PLN):

  • The average age of onset is 6 years (range 2 to 11 years).

  • Dogs will not usually exhibit symptoms until the disease is very advanced.

  • Left untreated, PLN is usually fatal.

  • Treatment is with medication and diet. Early intervention can result in a longer lifespan.

  • PLN is a condition in which plasma protein is lost to excess in the kidney.

  • In the SCWT the most common disease causing PLN syndrome is glomerulonephritis.

  • The term “glomerulonephritis” defines a group of inflammatory diseases of the kidneys affecting the most important functional components of renal tissue, the glomeruli and adjacent structures.

  • There are several immune mechanisms involved in this inflammatory disease.

  • SCWT's affected with PLN have damaged glomeruli because the ‘holes’ in the basement membrane are too large and allow more than waste to pass through.

  • One of the larger molecules that pass through the faulty membane is protein. That is why excess protein (Albumin) is found in the urine of SCWTs who have one of the diseases that causes PLN.

  • A Urinalysis test is one of the key factors to show protein loss associated with PLN far earlier than in a blood test.

  • Tests necessary to detect the presence of PLN are blood, urine and if necessary, a wedge biopsy. Go to the Testing Protocols page for further information.

  • Please refer to the Comparison Chart of Hereditary Diseases for signs and symptoms of this disease.

  • The mode of inheritance for PLN is not known, but in 2012, Dr Paula Henthorn and Dr Meryl Littman at the University of Pennsylvania School of Veterinary Medicine (Penn Vet - details click here) identified mutations in two genes associated with PLN.

  • Learn more about PLN here

Proteinuria or Protein Losing Nephropathy (PLN)?

Dr Littman’s Criteria for the SCWTCA Open Registry:

To meet the criteria for PLN as Dr Littman defined in the *SCWTCA Open Registry the dog must have:

  1. Protein loss in the urine
  2. Low Albumin (Alb) in the blood
  3. Low Total Protein (TP) in the blood

The dog has Proteinuria first and as the disease progresses it affects the Albumin and Total Protein.

Many Wheatens have Proteinuria that is controlled by medications and diets and the Albumin and Total Protein does not dip below the normal levels in the blood.

Vets might still consider the dog has PLN but actually the criteria Dr Littman set is defined by those three values and Dr Littman still uses this criteria.

So, you can have a dog with Proteinuria and it not develop into PLN.

For the SCWTCA Endowment Inc. Health and Pedigree database we use Dr Littman’s criteria. If Albumin and Total Protein stay normal they will be listed only as Proteinuria.

If you want to understand the history of this disease in the SCWT you should read what responsible breeders and the Breed Club do when confronted with a health problem in the breed - SCWTCA breeders set the bar high!

Use this link to read about the history of the Open Registry

Anna Marzolino

Chair, SCWTCA Endowment Inc., 2022

In Dr Littman’s 2016 document - ‘Recommendations Concerning Protein Losing Nephropathy in the SCWT’, she states:

“ … When a dog has proteinuria:

It could be due to pre-renal, renal, or post-renal causes. Even if the dog is a carrier of one or two copies of the PLN-Associated Variant Alleles, it should not be assumed to have PLN (renal cause) and will need a work-up, for instance to rule out urinary tract infection (UTI) tickbourne/heartworm disease, neoplasia, hypertension and consideration of other causes for PLN such as amyloidosis, lupus, shigatoxin (raw meat diet) etc. ….”

Please go to this link for the full document (pdf - opens in new page)

* Since the retirement of Dr Littman in 2016, the SCWTCA Open Registry is no longer active.

However, should a Wheaten be diagnosed or die of an hereditary disease then the SCWTCA Endowment Inc., Health & Pedigree database has now replaced the Open Registry to record all health information.

Dr Littman, VMD DACVIM, Professor Emeritus of Medicine (Clinician-Educator), University Of Pennsylvania School Of Veterinary Medicine, is still available for paid consultations.

Some useful links for your Veterinarian:

Efficacy of Telmisartan for the treatment of persisitent renal proteinuria in dogs, Click here for the Wiley research document - December 2020 (opens in new page)

IRIS consensus clinical practice guidelines for management of Glomerular disease in dogs. Click here for the Wiley On-Line Library (pdf - opens on new page).

Chronic Kidney Disease (CKD) - IRiS website

PLN-Associated Variant Genes Test

It is important when testing for the PLN-Variant gene that this includes both NPHS1 and KIRREL2 genes in the test. Further details on this link.

For the PLN-Variant Genes Test it is preferred that Penn Laboratory (PennGen) is used, as this enables continuity of research. In Europe and Scandinavia Laboklin Laboratories also offer the test but the result does not directly aid this research.

PennGen Laboratories, at the University of Pennsylvania School of Veterinary Medicine are, from April 2020, offering individual and combination genetic testing for PLN (and Microphthalmia and Degenerative Myelopathy) in Soft Coated Wheaten Terriers. Select this link for further details of costs. (pdf - opens on new page)

Free cheek swabs for this test are available (at present in North America only) via the SCWTCA Endowment Inc web page

Please note that links given to articles that are general in nature on external websites are not a substitute for your own Veterinarian's advice.

Test Results definitions (updated August 2017)

This table clarifies the reporting formats between PennGen and Laboklin tests results.

Genetic Term Definition What does this mean? Other Common Terms Results from Penn Results from Laboklin

Homozygous Negative

A dog without any of the variant alleles

A dog that has no copies of the variant alleles is at the least risk of developing PLN



No copies







A dog with one copy of the variant alleles

A dog with one copy of the variant allele is at medium risk of developing PLN




1 Copy




Homozygous Positive

A dog with two copies of the variant alleles

A dog with two copies of the variant alleles is at the highest risk of developing PLN, but this does not mean it will develop PLN


Both copies

Homozygous for the PLN causative mutation


PLN/PLN (Affected)

Affected refers to both copies of the allele,

it does not mean the dog is currently, or will be affected with PLN

Further reading - Differentiating Renal Dysplasia (Juvenile Renal Disease) from Protein Losing Nephropathy (PLN) in our Wheatens. Meryl Littman 2006 click here for pdf file