Familial Nephropathy
By Addi Pittman,
Chairman, ECSCA Health Education
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.
Lees,
George E. et al. "Early
Diagnosis of Familial Nephropathy in English Cocker Spaniels. Journal of the
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.
Copyright 2001 Addi Pittman. All rights reserved.
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