Attention Breeders: Ultrasound PKD clinics for disease severity coming soon!

Background

Polycystic kidney disease (PKD) is a well documented abnormality in domestic cats. Cystic kidneys can sporadically occur in any population of cats, but early onset and bilateral presentation is a hallmark to the hereditary form. PKD is not a new disease and has been reported for over 30 years in the literature. The heritable form of PKD may not have initially occurred in Persians as a new mutation, but perhaps in random bred cats. The breeding practices for any breed often cause strong line or inbreeding, founder effects from the use of popular studs or queens, reduced influx of new genes due to closure to outcrossing. All these normal breeding practices can unwittingly allow a deleterious gene to increase in frequency in a population. Unfortunatley, PKD does not have strong clinical presentations until the cats have been used for breeding and the presentation is similar to one of the most common causes of death for any cat, renal failure. Thus, PKD has easily gone unnoticed for many years and has spread throughout the unlucky Persian breed. Any breed that has purposely or accidently used Persians in their foundation or propogation should have the same concerns for PKD.

In Persians, the condition has been shown to be inherited as a single autosomal dominant gene. It is estimated over 37% of Persians have PKD, a breed that accounts for nearly 80% of the cat fancy. But many lines and catteries have been able to greatly reduce this frequency by using ultrasound screening methods and improved breeding practices.

Genetics

Early onset, bilateral presentation (both kidneys), and multiple cysts are all hallmarks of a heritable disease. The kidney cysts for PKD present early, generally before 12 months, but renal failure generally occurs at a later time, thus is considered a late onset renal disease. In the fancy cat breeds, PKD is inherited as an autosomal dominant condition. This implies that one one copy of the gene is required to produce PKD. Generally, 50% of a PKD postive cats' offspring will inherit PKD. A postive cat could potentially be homozygous for PKD, thus all offspring produced would have PKD. It is suspected that cats that are homozygous for PKD are not abundant and the homozygote form could be lethal in utero or present very severly and at a very early age. Further research is required to prove the effects of the homozygote condition.

Although the PKD gene is dominant, the entire genetic make-up of the cat will still influence the disease. It is not know why some cats are more severe than others and why mildly affected cats can produce severly affected cats and visa versa. Certain lines and the study of families will help to answer these questions.

For some reason, certain cats may have inherited the defective gene but not express the condition. This is likely due to the interaction of other genes in the cat. But, we do not have a good estimate of how frequently this occurs in cats, if truly at all. The human condition has 100% penetrance.

Affected cats should not be produced from cats that are negative for PKD. Several situations must be considered prior to questioning the heritability or penetrance of PKD.

1. Is the sire and dam absolutely correct?

DNA testing can be used to confirm parentage.

2. Was the ultrasound screening performed accurately:

a. Was the cat over 6 - 8 months of age?

b. Was the cat sitting still for the examine?

c. Was the person performing the ultrasound very well qualified?

d. Was the correct equipment used?

3. Do you have the correct test results for the correct cat?

(top)

Human & Mice PKD

Several forms polycystic kidney disease are known in humans and mice. An excellent site to use to research PKD in "Mendelian Inheritance in Man". A search here will present all the known heritable conditions in humans and extensive background information and references for each type of kidney disease. The four conditions most suspect for being similar to the cat condition are listed below. Whether a condition is dominant in humans, as in cats, may be a good indication of which gene to examine, but all genes should be considered.

POLYCYSTIC KIDNEY DISEASE 1; PKD1

This was the first gene found for PKD and resides on human chromosome 16p13.3-p13.12, mouse chromosome 17. This locus is also referred to as ADPKD (autosomal dominant PKD). This gene has been isolated in humans and mice and the exact mutations are known.

POLYCYSTIC KIDNEY DISEASE 2; PKD2

This was the second gene found for PKD and resides on human chromosome 4q21-q23, mouse chromosome 5. This condition is also autosomal dominant in humans. The PKD2 gene has been isolated in humans and mice and mutations causing the condition are known.

POLYCYSTIC KIDNEY DISEASE 3, AUTOSOMAL DOMINANT; PKD3

Less is known about this presentation of PKD. The location of the gene has not been determined and the gene has not been isolated in any species.

POLYCYSTIC KIDNEY AND HEPATIC DISEASE 1; PKHD1

This for of PKD is autosomal recessive in humans (ARPKD) and is found on human chromosome 6p21.1-p12. This gene has not yet been found in humans or mice.

(top)

Breeds

PKD is most common in the Persian breed and breeds that are related to Persians or have used them in their breeding programs. Examples include: Exotics, Himylayans, American Shorthairs and Scottish Folds. Others breeds could have accidently picked-up PKD from an accidental use of either a purebred or random bred, that had the heritable form of PKD. Rcently, we have discovered Ragdolls that are positive for PKD. We have not found PKD in Norwegian Forest Cats, Chartreux, American Wirehairs, Maine Coons and Birmans, but we have screened a limited number of cats from only a single or few catteries.

Clinical Presentation

Cysts can be present in the developing fetus. Cysts can range in size from 1 mm to over 1 cm and become larger and more abundant with age. The presence of cystic kidneys can be determined by 6 to 8 months of age by ultrasonic techniques and affection diagnosis is generally certain by one to two years. These ultrasonic evaluations have a 91% sensitivity and 99% specificity at 9 months.This means that there is some error if determining if a cat is postitive, but if ultrasound imaging indicates that the cat is positive, these results should be extremely accurate. Some cysts can be detected in utero!

Average age for renal dysfunction, not failure, is 7 years for cats with PKD. Thus, with out imaging techniques, cats would go undiagnosed for PKD for many years. Other clinical findings have included hepatic cysts.

Clinical signs are nonspecific but common to cats experiencing renal dysfunction, including: depression, anorexia, reduced appetite, polyuria, polydypsia, and weight loss.

Exterior Kidney with moderate presentation	Exterior Kidney with advanced PKD	Interior kidney with moderate PKD presentation

US of Kidney with PKD (Courtesy Dr. D. Biller)	US of Kidney with PKD (Courtesy Dr. D. Biller)

(top)

Clinical Management

No cure is available and clinical management is designed to prevent or minimize kidney failure and secondary conditions arising from poor kidney function. Diets that are less taxing to kidney functions can be considered. Drugs and clinical treatments that are taxing to the kidneys should be minimized. We have clearly seen from the PKD clinics that breeders are able to maintain a strong cattery while slowly eliminating PKD. Many of the returning catteries are drasxting reducing the incidence of PKD.

Humans also experience PKD, thus research in humans should be closely monitored for suggested new therapies. Tyrosine kinase inhibitors are currently being closely examined.

Gene Hunting and PKD Research

Extensive clinical diagnostics and managements have been under investigation on a large cat colony of Persian origin at Ohio and Kansas State Universities for nearly a decade. These studies have been lead by Drs. David Biller and Stephen DiBartola and have lead to reliable and robust diagnostic methods and standards. Drs. Biller and DiBartola have been involved with researchers (Drs. Leslie Lyons and Marilyn Raymond) at the Laboratory of Genomic Diversity (LGD) of the National Cancer Institute for several years regarding the identification of candidate genes for feline polycystic kidney disease. Blood samples, pedigree information and disease status has been relayed to the LGD to develop linkage studies and mutation screening of candidate genes. Dr. Lyons initiated a research grant to the Winn Foundation in 1999 and received the funding for the research in March 2000, after her move to UCDavis. Recently, the Lyons' laboratory at UC Davis has been successful with identifying the mutation that causes feline PKD. Please see testing information below.

Focus on continued feline PKD research at UC Davis

Copy of the Winn Foundation Research Grant

Copy of 6 months report and renewal grant to the Winn Foundation

Join the Project!

Breeders and cat owners cat assist the research for PKD in various ways. Some breeders have donated blood samples, PKD status and pedigree information for family studies. Others have donated blood samples from affected cats for mutation screening. Kidneys of deceased cats can be donated for analysis by researchers involved with human PKD studies. Collaborating owners can attend PKD clinics and have a majority of their cats screened for free or for a minimal cost. Some individuals choose to donate money to the Winn Foundation that is specifically marked for PKD research.

This research is not breed or association specific!

(top)

Contact the laboratory at UCDavis if you are interested in participating at: felinegenome@ucdavis.edu.

Information for sending samples can be found on this website at: DNA Sampling and Shipping Protocols

PKD References

Other useful links:

Veterinary Genetics Laboratory (VGL)

Center for Companion Animal Health (CCAH)

California National Primate Research Center (CNPRC)

Center for Equine Health (CEH)

Department of Population Health & Reproduction (VM:PHR)

Last update: November 30, 2004 This site is under continual development. Please visit again soon! Many of the current pages are the place holders for future information. Please provide suggestions to the webmaster: felinegenome@ucdavis.edu