Familial Nephropathy (FN)

Familial Nephropathy, an overview of this kidney disease by Addi Pittman

Introduction

Familial Nephropathy (FN) is a recessively inherited (Lees, Macdougall/Cattanach) renal disease that has been recognized in the English Cocker for more than 50 years (Krook 162).  FN is a form of "hereditary nephritis" (Lees 189) which refers to a group of glomerular diseases that are linked to genetic collagen defects.

Onset of renal failure due to FN typically occurs between six and 24 months of age (Lees 189).  Clinical signs may include polydipsia (drinks more), polyuria (urinates more), weight loss, lack of appetite, vomiting, or diarrhea.  These symptoms are commonly associated with any type of renal failure.

Structure/Function

The kidney is an organ made up of hundreds of thousands of tiny structures called nephrons.  Each nephron consists of a glomerulus and a tubule.  Blood flowing through the kidney is filtered by the glomerulus, with the fluid that is filtered out of the blood subsequently passing down the length of the tubule.  Cells that line the inner surface of the tubule process the fluid as it flows along, reabsorbing certain components of the fluid and excreting others. The fluid leaving the tubule at the end of this process is urine, which is a combination of water and waste products.

Dogs affected with FN have a genetic defect within the glomerulus.  This defective glomerulus lacks a certain type of collagen that helps to hold the structure of the filter together.  As a result of this collagen defect, a chain reaction of events takes place. Once the glomerulus begins to loose its ability to function properly, blood proteins leak through the defective filter into the urine.  The glomerular abnormality also leads to subsequent tubular damage, and the chain of events eventually destroys the entire nephron.  Nephrons that are severely damaged or destroyed can’t be replaced.

Since the kidney serves as the main waste-disposal system in the body, it is a master at compensation.   When one nephron dies, another takes over its work.  Over the course of time and with continual compensation the number of functioning nephrons is greatly reduced.  Once at least 75 percent of the nephron population is destroyed, end-stage renal failure occurs.  Since the disease is gradual and progressive, affected dogs do not appear sick until very late in the course of disease.

In the Beginning...

English Cockers affected with FN are born with normally developed kidneys.  Because they lack a certain type of collagen, however, the kidneys begin to deteriorate while the dogs are just a few months old.  As   glomerular damage evolves, the kidneys will first allow protein (proteinuria) to escape into the urine.  Generally, while proteinuria persists, the pup’s growth rate will slow down.  Once the pup begins to spill protein into the urine, the ability of the kidneys to ‘concentrate’ the urine will also diminish.  Finally, as a result of progressive nephron damage, the ability of the kidneys to excrete waste products (eg, urea and creatinine) will become impaired (Lees).  As excretion of waste products by the kidneys progressively diminishes, the severity of renal failure will gradually worsen.

Sequence of Events

The sequence of events is always the same, but the rate of disease progression varies for reasons that are not fully understood (Lees).  As a result, it is difficult to give a specific age when to expect various stages of the disease to take place.  "For example, onset of proteinuria was at 5 to 8 months of age in 3 dogs in which it was carefully studied.  Because we can’t be sure that these 3 dogs are representative of all FN-affected dogs, we are uncertain what age to say is the oldest an FN-affected dog can be when  it first has proteinuria.  Nonetheless, we suspect that all, or almost all, dogs with FN will have proteinuria before a year of age.  The age range for occurrence of renal failure is 6 months to 2 years" (Lees).

Clinical Signs

    One way to identify a pup that might have FN is through observation.  Breeders and owners can watch the voiding patterns of young dogs.  Make it a point to regularly check the color of the urine.  The first morning release (assuming water hasn’t been available during the night) is probably best.  There should be good yellow color (well concentrated).  A youngster that lacks the ability to pass concentrated urine repeatedly should be taken to a veterinarian for a complete urinalysis.  A test called a "specific gravity (SG)" should be performed as well as an analysis for protein (proteinuria).  Usually, protein can be checked by using a color-coded plastic strip (Bili-Labstix).  This strip is merely dipped into a urine specimen and the plastic strip changes color and is checked against a chart on the side of the bottle the strips come in.  This strip will test for several things other than protein.  A pup with a low specific gravity and  excess protein (++) in the urine should be tested using a more specific test.  This test, a ‘protein-creatinine ratio,’ will provide a better estimate of the amount of protein in the urine.  A complete urinalysis should also be done to identify other urinary problems that may be present.  A positive dip-stick for protein does not necessarily indicate that the dog has renal disease or will develop FN.  It’s merely an indication that a more thorough evaluation is needed.  Not all young-age renal failure in this breed is FN; however, the symptoms are the same.

End Stage

 Once it is established that a young dog is consistently passing dilute urine with protein, serum chemistry tests should be performed.  Such tests will only show significant elevations in specific areas once 75% of both kidneys are destroyed.  Elevations in BUN (blood urea nitrogen), creatinine, and inorganic phosphorus suggest kidney disease.  These findings coupled with a low urine specific gravity and proteinuria signal end-stage renal disease.

When the serum chemistry tests show "abnormally high levels of urea (BUN), creatinine, and other non-protein nitrogenous substances, a laboratory term called Azotemia is used to identify these specific abnormal levels (Barrett 1753)."

Generally, once the BUN reaches approximately 120 mg/dl, the dog only has a few weeks before critical illness sets in.  When these animals become critically ill, they will not eat.  If they do eat, they usually vomit.  They may go for two or three days without food, loosing more weight.  They will drink a tremendous amount of water and urinate even more.  Sometimes there will be an ammonia odor from the mouth.  Since the dog sleeps on the ear leathers, this ammonia odor may be apparent on the ear furnishings.  The dog will become very weak, and may tremble as if it’s cold.  They loose the ability to regulate their body temperature.  Since the kidney’s are no longer able to filter the body’s waste products, and regulate many important functions essential for life, the animal is essentially poisoning itself with its own waste products.

Perhaps one of the most frequent questions asked by owners with a young dog in failure is how will they know when it’s time to say good-bye.  Despite being in the critical stage of renal failure, these youngsters can always manage to wag their tail and greet family members, not with the usual exuberance, but the effort is there until the end.  When the time comes to say good-bye you’ll know…

Those that have lost a dog to FN will tell you the loss is more profound with this disease process than any other they’ve experienced.  It’s something no one wants to experience.  Through the efforts of Dr. George Lees and his research team, hopefully in the very near future the mutation will be found.  This will enable the development of a mutation-based DNA test that will unequivocally identify carrier animals.

Currently, a research fund has been set-up at the Texas A&M Development Foundation to honor the memory of Arthur B. Ferguson.  Arthur expressed a desire to help researchers find a means to end this disease.  Appropriately titled, Arthur B. Ferguson Memorial Fund for English Cocker Spaniel Kidney Disease Research. 

Donations to this fund can be made in the following manner;

  1. Make the check payable to: Texas A&M Development Foundation;
  2. In the "For" space write: Ferguson Memorial Fund;
  3. Send your check to: Dr. George E. Lees  Small Animal Medicine & Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 78843-4474.   Donations to the Memorial are the only means we have right now to continue the research until a new grant can be secured. This fund is classified a 501-C3 tax contribution.

Join the fight to end FN in our breed.

Addi Pittman, Chairperson
ECSCA Health Education


 

Works Cited

Lees, George.  Personal correspondence.  25 Sept , 1999.

Lees, George E.  et al.  "Early Diagnosis of Familial Nephropathy in English Cocker Spaniels.  Journal of the American Animal Hospital Association.  May/June 1998, Vol. 34: 189-195.

The Cocker Spaniel Club.  "Familial Nephropathy (FN) of Cocker Spaniels. An advisory leaflet for all Cocker owners."  September 1986.

Krook, Lennart.  "The Pathology of Renal Cortical Hypoplasia in the Dog.  Nord. Vet.-Med. 1957, 9, 161-176.

Barrett, Ralph E.  "Textbook of Internal Veterinary Medicine."  Azotemia and Proteinuria.  Section 11, Chapter 21, 141-145.

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