Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder in humans, occurring in 1 in 200 to 1 in 100 people. The disease occurs in all races, affecting as many as five million people worldwide, and accounts for approximately 10% of renal dialysis patients. A form of ADPKD similar in clinical features to human ADPKD occurs in Persian and Persian crosses.

In approximately 85% of human patients with ADPKD the disease is caused by a mutation in the PKD1 gene located on chromosome 16p13.3. The remaining 15% of affected ADPKD patients were discovered to be a result of a defective PKD2 gene on chromosome 4q21-23 or an unidentified, but suspected third genetic locus. Similar to PKD1, PKD2 encodes for 'an integral membrane protein', and the homology between the two proteins exists. There are additional genes that are known to cause different types of polycystic kidney conditions in humans. The clinical signs of this disease often overlap, therefore in humans DNA testing is required to determine which gene is causing the clinical presentation. Diseases that have similar clinical presentation are called heterogenous diseases. Because of the disease heterogeneity in humans it was difficult to find out which gene caused polycystic kidney disease in cats.

Study of the pathogenesis of cyst formation and growth in ADPKD has been limited because of the lack of availability of animal models that closely mimic the human disease. Several models of autosomal recessive polycystic kidney disease (ARPKD) that closely mimic human ADPKD have been described. In addition, the pcy mouse model of ARPKD shows some similarities in clinical features to human ADPKD but differs in morphology and inheritance. The clinical and morphological similarity of ADPKD in Persian cats to human disease and the autosomal dominant pattern suggest that this disease represents a good model for ADPKD in humans.

Autosomal dominant polycystic kidney disease (PKD) is a progressive, inherited condition which causes multiple fluid filled cysts on the kidneys of Persians/Exotic cats and other long haired breeds. The latest studies reveal the prevalence of PKD in Persian cats to be very high (37-49%) compared with approximately 5% in non-pedigree cats. No sex predilection has been recorded. 

Cysts are present in the renal cortex and medulla and occasionally in the liver, pancreas and uterus. Although the dysfunction of the kidney does not occur until mid to late in life, the cysts are present from birth, starting out as small cysts and slowly increasing in size. Cysts can range from very small to several centimetres in diameter, and may affect one or both kidneys, with older animals having larger and more numerous cysts. The number of cysts also varies from one to more than 200 per kidney. There is a marked difference in when and how quickly cats succumb, with the possibility of a long enough life that a PKD cat can die of other causes before kidney failure. However, it is never certain when the cysts will grow and cause problems. 

A parallel disease in humans can also cause systemic hypertension, cysts in the pancreas and uterus, cerebral and intracranial aneurisms and cardiac valvular dysplasia. These manifestations can also occur in cats with PKD as the similarities between the two diseases is striking. Severely affected kittens may die at 8 weeks of age; however, the disease is usually subclinical (not noticed) for several years.

The increasing size of the cysts damage the normal kidney tissue, eventually causing kidney failure. The number of cysts and the speed and size in which they grow varies from cat to cat. The average age of kidney failure in cats with PKD is 7 years, but some cats will suffer from kidney failure at an earlier age and some cats much later, and in fact succumb to something other than PKD. 

Clinical Symptoms

Polycystic disease is a disease that shows up later in life (late onset) with enlarged kidneys and kidney dysfunction occurring between three and 10 years of age (on average at seven years of age). The condition is inherited and cysts are present from birth, but are smaller in younger animals. Cyst size can vary from less than 1 mm to greater than 1 cm in size, with older animals having larger and more numerous cysts. Problems occur when these cysts start to grow and progressively enlarge the kidney, reducing the kidney's ability to function properly.

Symptoms of PKD are usually related to acute renal failure and include weight loss, lethargy, vomiting, increased thirst (polyuria), increased frequency of urination and sometimes a strong urine-like breath. The ultimate end is kidney failure. Some of the clinical signs are depression, lack of or reduced appetite, excessive thirst, excessive urination and weight loss. There is a marked difference in when and how quickly individual cats succumb, with the possibility of this developing late enough in life that the cat can die of other causes before kidney failure. However, kidney failure is certain when the cysts can grow and cause problems. Rarely, cysts are also seen in other organs such as the liver and uterus. 

Figs. 1-3 showing disease progression of PKD from normal (left) to end stage disease (right)

Diagnosis

PKD is most easily diagnosed by ultrasound. Ultrasound is a non-invasive imaging technique that can identify the disease very early in its course. All that is required is a mid-ventral abdominal area hair clip and a short time period for imaging to detect the presence of cysts. With the proper equipment and experienced personnel, this can be done as early as eight weeks of age. Usually, the older the cat the larger the cysts and the easier to detect. Ultrasound diagnosis is 98% accurate after approximately 10 months of age¹. 

The sonographic features of renal cysts include: a round-to-ovoid contour; anechoic contents; smooth, sharply demarcated thin walls with a distinct far-wall border, and strong distal acoustic enhancement. Cysts may deform the kidney outline if they are large. High frequency transducers are required to give sufficient resolution and a 7.0 MHz transducer, or higher should be used. The medulla is hyperechoic to the renal cortex; therefore it is easier to detect cysts in the cortex in comparison to the medulla. Ultrasonography has a sensitivity of 75% when performed at 16 weeks of age and a sensitivity of 91% when performed at 36 weeks of age. Research has shown that the absence of cysts on ultrasound examination at 6 months of age was correlated with absence of PKD at necropsy.

PKD can be diagnosed genetically. In Australia, most veterinary pathology laboratories, such as IDEXX and Gribbles, provide the test directly to cat breeders. Animal DNA laboratory also tests for PKD. Samples are taken via a buccal (mouth swab). A positive test infers that the cat has the genes predisposing to PKD. In breeding queens, a positive test necessitates desexing so as to stop spreading the disease. PKD is caused by an autosomal dominant gene (one which shows itself if it is present, even if inherited only from one parent). This means that a PKD-free cat is also genetically PKD-free. If a cat is PKD positive, then it must be either heterozygous (inherited the gene from one parent) or homozygous (inherited the gene from both parents).

Treatment

There is no specific treatment for this disease. Supportive therapy is similar to treatment of chronic kidney failure of any cause. This includes moderate dietary protein restriction using high biological value protein (e.g. Hills K/D diet), dietary phosphorus restriction, providing fresh drinking water at all times, use of phosphate binders, and treatment of the anaemia if necessary. Peritoneal dialysis has been used as an adjunct therapy that will help prolong some cats. Euthanasia is usually elected when quality of life deteriorates to the point where the cat is no longer eating.

Elimination of PKD from a cattery

As PKD is the result of an autosomal dominant gene, it is relatively easy to track and eliminate. All breeding animals need to have an ultrasound to detect the presence of kidney cysts. It takes a few minutes with little or no sedation needed. If positive, then go back (if possible) and check parents. The quickest way to eliminate the problem is to neuter and spay these individuals. Littermates and parents of affected cats should have sonograms because asymptomatic disease may be present for many months and years. Early detection permits early therapy to support renal function and recommendations against breeding of affected individuals.

If a particular breeding stud or queen is extremely valuable, then it is still possible to produce kittens that are PKD negative (if the other parent is PKD negative and the PKD positive parent is heterozygous). When the kittens are old enough, an ultrasound can be performed to determine their PKD status. This way a replacement of the concerned bloodline can be chosen and the affected parent neutered. It is theorized that PKD is far more common in Persians than is currently diagnosed.

1. www.catworld.com.au