Active Studies for Bladder & Kidney Disease

Click to view the current studies:

• Bladder Cancer
• Kidney Disease

Bladder cancer – Urothelial cell carcinoma (UCC), previously known as transitional cell carcinoma (TCC)

There are 2 active research groups that have studies in which Shetland Sheepdog owners can participate.

Research Group 1: Ostrander Laboratory at the National Human Genome Research Institute at NIH

Because the observed differences in breed susceptibility to UCC is strong evidence of a genetic predisposition, the Ostrander laboratory has been looking for inherited genetic variants underlying this risk.

They analyzed 100 Shelties (49 cases and 51 apparently healthy controls aged 10 years or older) and 55 dogs from related breeds (collie, border collie, Australian shepherd; 21 cases and 34 controls). The researchers identified a mutation in the NIPAL1 gene on chromosome 13 that they suspect is a major risk locus for UCC in dogs (Parker et al., 2024). It is associated with an approximately 3-fold increase in risk of UCC when present in a single copy (heterozygous) and an approximately 8-fold increase when present in two copies (homozygous). They found six additional risk loci on chromosomes 1, 4, 9, 21 (two loci), and 28. All told, the seven loci account for about three quarters of the risk of UCC in the dogs they studied. Evaluations of additional dogs will be needed to validate their findings.

This study is ongoing and more participants (healthy dogs over 10 years old and dogs with confirmed bladder cancer) are needed. Also, if you have entered your dog into the study, updated health information is requested. See information about the findings of this study and how to participate.

Reference:

Parker, H.G., Harris, A.C., Plassais, J. et al. Genome-wide analyses reveals an association between invasive urothelial carcinoma in the Shetland sheepdog and NIPAL1. npj Precis. Onc. 8, 112 (2024). https://doi.org/10.1038/s41698-024-00591-0

Research Group 2: The NC State University College of Veterinary Medicine is currently recruiting dogs for 2 clinical studies:

Principal investigators: Drs. Shelly Vaden and Matthew Breen

Be advised that for both studies, dogs selected for inclusion will need to be brought to the NC State University College of Veterinary Medicine periodically.

Clinical Study 1. Early Detection Screening of Dogs for Bladder and Prostate Cancer

This study is screening urine samples from clinically healthy dogs of breeds with an increased risk of bladder/prostate cancer, to identify those that test positive for a genetic marker of the disease (a specific mutation in the dog BRAF gene). This test was developed at North Carolina State University (NCSU) and is referred to as the NCSU BRAF mutation detection test. The goal of the study is to determine the time period between detection of the genetic marker in urine of healthy dogs and the development of clinical signs of bladder/prostate cancer.

Clinical Study 2. Therapeutic Trial for Dogs with Bladder Cancer

This study is a double-blinded therapeutic trial of a nutritional supplement for dogs commencing treatment following a recent diagnosis of bladder cancer. The goal is to determine whether the addition of the supplement to a conventional treatment regimen improves survival for dogs diagnosed with bladder cancer.

Read more about these studies at https://www.breenlab.org/early-detection-of-canine-urothelial-carcinoma  

Please complete the following questionnaire to register your interest in participating. https://redcap.link/NCStateUCStudyQ1

Contact UCClinicalTrials@ncsu.edu  with any questions.

Update: The recruiting phase of the studies at NC State has ended. Data analysis is in progress. The researchers reported “tremendous engagement with Sheltie owners and fascinating results. Links to study results will be posted when available.

Characterization of Kidney Disease in Shetland Sheepdogs

Do you own a Shetland Sheepdog that has been diagnosed with kidney disease or is related to one with kidney disease? The American Shetland Sheepdog Association and its charitable Foundation are sponsoring a study which might help determine if there is an inherited link to kidney disease in Shetland Sheepdogs.

How you can help

PHASE 1- Collection of Historical Data

1. Provide a complete pedigree of your pet, which includes identification of any relative with a diagnosis of kidney disease.
2. Share all medical records from those individuals diagnosed with kidney disease.
3. Provide access to any kidney tissue and/or laboratory values (e.g., bloodwork) which might have been previously tested.

PHASE 2- Sample Collection from Pedigreed Families where Kidney Disease is Prevalent (Concurrent with Phase 1)

1. Kidney samples via biopsy or autopsy (dogs with kidney disease): If your veterinarian recommends performing a kidney biopsy to determine the cause of your Sheltie’s kidney disease, or if your dog has a diagnosis of kidney disease and is euthanized for any reason, kidney samples can be submitted to the International Veterinary Renal Pathology Service (IVRPS) at Texas A&M University for evaluation. Biopsy samples should be collected early in the disease process to provide the best interpretation and guidance for treatment of the disease. A particularly good opportunity for collection of a kidney biopsy is at the time of spay. *  Monetary support for the cost of kidney biopsies may be available from the ASSA Foundation (see below).
2. Blood and urine (dogs with kidney disease or related unaffected dogs): If kidney tissue is provided, blood and urine should be submitted concurrently for additional analyses and isolation of DNA. DNA would be used to search for causative gene(s) and ultimately development of a DNA test if a hereditary cause is found. If kidney tissue is not provided, then blood and urine can be submitted for evaluation, which can help determine the extent to which your dog’s pedigree is affected. Evaluations of all submitted samples will be performed at no cost to the owners and all results will be provided through their veterinarians.

*The owner’s veterinarian should obtain a free biopsy collection kit prior to the biopsy procedure as specialized tissue fixatives are needed.

For more information, go to the Texas A & M study website at https://studypages.com/s/characterization-of-kidney-disease-in-shetland-sheepdogs-973053/ or contact:

Dr. Mary Nabity, IVRPS, mnabity@tamu.edu – 979-845-9172
Dr. Jessica Hokamp, IVRPS, jhokamp@tamu.edu – 979-845-9192
Or send an email to: IVRPS@tamu.edu, attention: Drs. Mary Nabity & Jessica Hokamp

Monetary support for the cost of kidney biopsies from the ASSA Foundation

The determination of whether or not an inherited kidney disease process is likely in the Shetland Sheepdog will depend upon the analysis of kidney tissue obtained from as many affected dogs as possible. Kidney biopsies can be helpful to determine diagnosis and guide treatment in dogs with kidney disease, as we currently lack non-invasive diagnostic tests to accurately identify most types of kidney disease. Kidney samples obtained early in the disease process are more likely to yield helpful information than that obtained late in the process when much of the tissue has been scarred. However, tissue obtained shortly after death will still be useful and when possible, biopsy collection kits should be requested in advance.

When biopsies are considered diagnostically appropriate for an affected dog based on evaluation by a veterinarian, the cost may be partially subsidized by the ASSA Foundation. Up to $500 each for the first 10 Shelties biopsied has been reserved for that purpose*. Applications for subsidies must be approved by either Dr. Nabity or Dr. Hokamp prior to collection of tissue. Because the cost of obtaining kidney tissue in a live dog is greater than that obtained after death, subsidy funds are reserved for tissue obtained from live dogs.

Procedure:

1. The dog’s veterinarian or owner must contact either Dr. Nabity or Dr. Hokamp to determine if the biopsy procedure would be eligible for subsidy and to arrange for delivery of a kit to the veterinary clinic if the biopsy is intended to proceed (regardless of subsidy eligibility).
2. If eligible, a form will be sent to the veterinarian to complete and return with the biopsy sample.
3. After the biopsy sample, blood and urine have been received by the laboratory, the completed form will be sent to the ASSA Foundation Treasurer who will issue a check for up to $500 to the veterinarian. Because of IRS rules, the Foundation cannot issue checks directly to the owner.

*Kidney biopsies from many more affected Shelties will be needed for evaluation of kidney disease in this breed.  Funds for additional subsidies may or may not be available.

Approval will be based on the following:

• Purebred Shetland Sheepdogs.
• Pedigrees and medical records have been received by the researchers.
• Blood for DNA, serum, and urine is intended to be collected and sent with the kidney biopsy.