Protein-Losing Nephropathy (PLN) in Dogs and Cats

TL;DR. Protein-losing nephropathy (PLN) is a serious kidney disorder in dogs and cats where the kidneys leak vital proteins into the urine, leading to fluid retention, high blood pressure, and potentially life-threatening blood clots.

Fluid accumulation in the abdomen (ascites) is a common sign of advanced protein-losing nephropathy.

What is it?

Protein-losing nephropathy (PLN) is not a single disease, but rather a group of serious kidney disorders that affect dogs and cats. To understand PLN, it helps to picture how a healthy kidney works. Inside each kidney are hundreds of thousands of microscopic filtering units called glomeruli. These structures act like tiny, highly selective sieves. They allow waste products and excess water to pass through into the urine while keeping essential components—like blood cells and large proteins—inside the bloodstream.

In a pet with PLN, these microscopic filters become damaged and "leaky." As a result, vital proteins, particularly a protein called albumin, slip through the filters and are lost in the urine. This persistent, severe loss of protein is called proteinuria. Because albumin is the primary protein responsible for holding fluid inside the blood vessels, its loss leads to low blood protein levels (hypoalbuminemia). Without enough albumin, water leaks out of the blood vessels and pools in the surrounding tissues, causing swelling in the limbs (edema) or fluid accumulation in the abdomen (ascites).

The glomerulus acts as a microscopic sieve, which becomes damaged and leaky in pets with PLN.

Beyond fluid retention, PLN triggers a cascade of other systemic problems. The kidneys play a critical role in regulating blood pressure. When they are damaged, they retain excess sodium and overactivate a hormone system called the renin-angiotensin system (RAS). This leads to systemic hypertension (high blood pressure). Additionally, the kidneys leak out proteins that normally prevent blood clots from forming. Without these protective proteins, the pet's blood becomes hypercoagulable, meaning it is highly prone to forming dangerous, life-threatening blood clots (thromboembolism).

Causes & risk factors

PLN can develop as a primary, inherited condition or secondary to other underlying diseases. The two most common pathological processes that cause PLN are glomerulonephritis (inflammation of the glomeruli) and amyloidosis (the abnormal deposition of a protein called amyloid in the kidney tissues).

Many cases of glomerulonephritis are immune-mediated, meaning the pet's own immune system creates antibody complexes that get trapped in the glomerular filters, causing chronic inflammation and damage. This can be triggered by chronic infections, inflammatory diseases, or cancers. In other cases, genetic mutations cause the glomerular filters to develop abnormally.

Several dog and cat breeds have a known or suspected genetic predisposition to developing PLN. For example, Soft-Coated Wheaten Terriers, Brittany Spaniels, and Bernese Mountain Dogs are well-documented as having familial forms of glomerular disease. Other breeds, such as the Samoyed, Chinese Shar-Pei, and English Cocker Spaniel, also carry significant genetic risks. In cats, breeds like the Siamese Dog and Oriental Shorthair have been noted, though feline PLN is generally less common than canine PLN, and much of our clinical guidance for cats is extrapolated from canine medicine.

Signs to watch for

The signs of PLN can be subtle in the early stages, often starting with mild changes that are easy to miss. As the disease progresses and kidney function declines, more severe symptoms emerge.

• Proteinuria (Cardinal): Excess protein in the urine. This is the hallmark sign of PLN, though it cannot be seen with the naked eye and must be detected through laboratory tests.
• Hypoalbuminemia (Common): Low levels of albumin in the blood, identified via routine blood work.
• Edema (Occasional): Swelling in the limbs, face, or under the chest due to fluid leaking from blood vessels.
• Ascites (Occasional): A distended, fluid-filled abdomen.
• Polyuria and Polydipsia (Occasional): Increased urination and increased thirst, which occur as the kidneys lose their ability to concentrate urine.
• Weight Loss and Vomiting (Occasional): General signs of chronic kidney disease and the buildup of toxins in the blood (uremia).
• Blindness (Rare): Sudden loss of vision, which occurs if severe high blood pressure causes the retinas to detach.
• Dyspnea (Rare): Sudden, severe difficulty breathing, which is a medical emergency typically caused by a blood clot traveling to the lungs (pulmonary embolism).
• Paraparesis (Rare): Sudden weakness or partial paralysis of the hind limbs, caused by a blood clot blocking blood flow to the legs.

Pets in the advanced stages of chronic kidney disease associated with PLN may also display a poor body condition, a dull or dry haircoat, dehydration, oral ulceration, and small, irregular kidneys felt during a physical exam.

Peripheral edema, or swelling of the limbs, occurs when fluid leaks from blood vessels due to low protein levels.

How vets diagnose it

Diagnosing PLN requires a systematic approach to confirm that protein is indeed leaking from the kidneys and to rule out other potential causes. As a leading veterinary internal medicine reference notes:

"A diagnosis of protein-losing nephropathy (PLN) is made by documentation of persistent proteinuria that cannot be explained by inflammation of the lower urinary tract or blood contamination of the urine."

Your vet will begin with a comprehensive physical exam and a series of core diagnostic tests:

• Urinalysis: This is the first step. The vet will use a urine dipstick to estimate protein levels. However, because dipstick results can be influenced by how concentrated the urine is, they must be interpreted alongside the urine's specific gravity and sediment. The vet must ensure there is no active infection, inflammation, or blood in the urinary tract that could falsely elevate protein levels.
• Urine Protein-to-Creatinine (UPC) Ratio: Once persistent proteinuria is confirmed, the vet will order a UPC ratio to precisely quantify the protein loss. To get the most accurate picture, your vet may recommend pooling three separate urine samples collected over different days. This is often a highly cost-effective alternative to running multiple individual tests.
• Blood Pressure Measurement: Because high blood pressure is a common and dangerous complication of PLN, regular blood pressure monitoring is essential.
• Renal Biopsy: This is the gold standard diagnostic test. A biopsy is the only way to determine the exact type of glomerular disease affecting your pet (such as amyloidosis versus glomerulonephritis). Knowing the specific pathology helps your vet tailor the treatment plan.

Regular blood pressure monitoring is essential to detect and manage systemic hypertension in pets with PLN.

It is important to note a clinical paradox regarding the UPC ratio. As glomerular disease advances and the kidneys lose their filtering capacity, the overall glomerular filtration rate decreases. Because less blood is being filtered, the total amount of protein leaking into the urine may actually decrease, causing the UPC ratio to drop. As a leading veterinary textbook warns:

"As glomerular disease advances and glomerular filtration rate decreases, less protein is filtered and the UPC ratio may decrease, usually as the azotemia worsens. Such a decrease does not necessarily indicate clinical improvement and is a poor prognostic sign."

Treatment options

Treatment for PLN is multi-faceted, focusing on reducing protein loss, managing blood pressure, preventing blood clots, and controlling fluid retention.

First-Line Therapies

The primary goal of initial treatment is to lower the pressure within the glomerular filters, which helps reduce the amount of protein leaking into the urine.

• Angiotensin-Converting Enzyme (ACE) Inhibitors: Medications such as Enalapril or Benazepril are the standard first-line treatments. These drugs dilate the blood vessels leaving the kidneys, reducing filtration pressure and protecting the remaining kidney tissue.

Second-Line Therapies

If first-line medications are not enough to control high blood pressure, additional medications are introduced.

• Calcium Channel Blockers: Medications like Amlodipine are highly effective at dilating systemic blood vessels to bring severe high blood pressure down to a safe range, protecting the eyes, brain, and heart.

Supportive and Preventive Medications

• Antithrombotics: Because pets with PLN are at a high risk of developing life-threatening blood clots, your vet may prescribe Aspirin (a nonsteroidal anti-inflammatory drug that acts as a platelet aggregation reducer) to help keep the blood flowing smoothly.
• Diuretics: If your pet has significant fluid retention, an aldosterone antagonist and potassium-sparing diuretic like Spironolactone may be used to help the body eliminate excess fluid without depleting vital potassium.
• Anti-inflammatory / Antifibrotic Drugs: For pets diagnosed with amyloidosis, medications like Colchicine may be prescribed to help reduce inflammation and slow the deposition of abnormal proteins, though its effectiveness is highest when started early in the disease process.

Prognosis

The long-term outlook for pets with PLN varies significantly depending on the underlying cause of the disease.

• Amyloidosis: This form of PLN is progressive and carries a poor prognosis. Despite treatment, survival times are generally less than one year from the time of diagnosis.
• Glomerulonephritis: The course of this disease is highly variable. Some pets experience spontaneous remission or remain stable with mild, manageable proteinuria for years. Others may experience a progressive decline, eventually leading to chronic kidney disease and kidney failure.

Because feline PLN is relatively rare, long-term prognosis data specifically for cats is limited, and veterinary guidance is often extrapolated from canine cases. Regular monitoring of blood pressure, kidney values, and urine protein levels is essential to adjust treatments and maintain your pet's quality of life for as long as possible.

Prevention

Because most cases of PLN are caused by genetic predispositions or unpredictable immune-mediated responses, the disease is generally not preventable.

However, for breeds known to be at high risk, proactive screening is the best defense. Regular urinalysis and blood pressure checks during annual veterinary exams can detect early-stage proteinuria before clinical symptoms appear. Early detection allows for prompt intervention with ACE inhibitors, which can significantly slow the progression of the disease and extend your pet's life.

When to call your vet

If your pet has been diagnosed with PLN or belongs to a predisposed breed, you should monitor them closely for any changes in behavior or physical appearance. Contact your vet if you notice gradual weight loss, a dull coat, decreased appetite, or mild swelling in the paws.

EMERGENCY RED FLAGS: Seek immediate, emergency veterinary care if your pet displays any of the following signs:

• Sudden onset of difficulty breathing (dyspnea), which may indicate a blood clot in the lungs.
• Sudden weakness or inability to use the hind legs (paraparesis), which may indicate a blood clot blocking blood flow to the limbs.
• Sudden blindness or dilated pupils, which can occur due to retinal detachment from a sudden spike in blood pressure.

For specific breeds

Several breeds have unique genetic links to PLN:

• English Cocker Spaniel: Inherited as an autosomal recessive trait.
• Samoyed: Inherited as an X-linked dominant trait, meaning males are often more severely affected at a younger age.
• Soft-Coated Wheaten Terrier: Often associated with an abnormal immune response to dietary antigens.
• Brittany Spaniel: Associated with a hereditary deficiency of the third component of complement (a part of the immune system).
• Bernese Mountain Dog: Frequently associated with positive serology for Borrelia burgdorferi (the bacteria that causes Lyme disease), suggesting an infectious or immune-mediated trigger.
• Chinese Shar-Pei, Siamese Dog, Oriental Shorthair, Doberman Pinscher, Bull Terrier, Beagle, English Foxhound, and Abyssinian Sand Terrier: These breeds have suspected or documented familial predispositions to glomerular disease, requiring careful monitoring throughout their lives.

As noted in a leading veterinary internal medicine reference:

"Any breed can be affected by glomerular disease but familial forms of membranoproliferative GN have been reported in softcoated Wheaten Terriers (thought to be associated with abnormal processing of dietary antigens), Brittany Spaniels (associated with hereditary deficiency of the third component of complement), and Bernese Mountain Dogs (often associated with positive serology for Borrelia burgdo"

Sources

• Textbook of Veterinary Internal Medicine, 5th Edition, pages 692, 693, 696, 1469.