Canine Hyperuricosuria By Donna Patterson
The following is an excellent article regarding Hyperuricosuria by Donna Patterson. This article is reprinted with permission. Thank you Donna.
Big word. Big problem.
Hyperuricosuria means elevated levels of uric acid in the urine. This will predispose dogs to form stones in their bladders and sometimes kidneys. There are several types of stones that can develop in dogs:
1. Struvite Bladder Stones –composed of magnesium, ammonium, and phosphate. More common in female dogs.
2. Calcium Oxalate Bladder Stones - These stones are formed in dogs that have a hereditary condition whereby they lack a calcium binding glycoprotein which inhibits the growth of calcium oxalate crystals in the urinary tract.
3. Uric Acid Bladder Stones - genetic in nature and caused because the liver cannot absorb uric acid.
The type of stones that we are concerned with here are the uric acid bladder stones.
Dalmatians are predominately affected by this disease. In fact, in Dalmatians only the mutant form of the identified gene (the SLC2A9)
occur, so all Dalmatians are affected and susceptible to urate bladder stones. In Black Russian Terriers and Bulldogs the disease is an autosomal recessive, which means that for a dog to be affected with the disease it must have two copies of the mu-tation in SLC2A9, one inherited from each parent.
The gene mutation was discovered by Dr. Danike Bannasch at the University of California (Davis). The complete research paper detailing the genetic identification and abnormality is available at: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000246. It is very detailed….much more than my intent to discuss here, but is interesting to read through.
Although Dalmatians are fixed for Hyperuricosuria (meaning all are affected), that is not the case in the Black Russian Terrier and Bulldog. We are still at the point where genetic testing and selection can eliminate the disease.
My interest in this started several years ago when I learned that UC Davis was conducting free testing on Black Russian Terriers. At that time I tested both of my dogs and found that Luba (Ebonies Pride Moya Lubov) is N/HU...a carrier of the mutation, but not affected. Best Guard Baikal (now deceased) was N/N ...clear of the mutation. Zil (Ch Zilya’s Chicago Blues Fusion at Runes), is N/HU, also a carrier but not affected.
The chart below shows the expected results when breeding nor-mal/carrier/affected dogs. As you can see, breeding normal males to normal females gives 100% normal puppies. Conversely breeding affected to affected will give 100% affected dogs with 2 copies of the genetic mutation that predisposes urate stone development. The breeding of two carriers will result in an expected 25% normal, 50% carriers, and 25% affected litter.
UC Davis has not yet published the frequencies of the mutation in Black Russian Terriers. From the very small sampling of owners who have wished to make their results public, it is fairly easy to see that this mutation is fairly common in the Black Russian Terrier and very careful breeding will be required to keep the BRT from becoming fixed with the mutation as is the Dalmatian. My problem with the studies currently is that there is no assurance that the genetic marker currently being used is really the one that indicates the likelihood of dogs forming stones. There are many, many affected (2 copies of the genetic marker) BRTs that show no problems or symptoms of stone formation. There has to be some other explanation of why only a small percentage of the affected dogs go on to produce stones. Either this is really a polygenic disease (as is hip dysplasia) where several genes have to combine to create the stone formation or there are environmental factors that cause an affected dog to form stones. The HU problem in the breed is a relatively new study and there are currently more unknows about the mechanics of stone formation than there are known factual information presented with studies to back it up. We all know of many instances where medical information was presented to the public (eat eggs/don't eat eggs, drink coffee/don't drink coffee, avoid alcohol/some alcohol is good) as dogma at the time of the initial study which has since been discredited or re-evaluated. UC Davis has not undertaken a long term study of the number of affected dogs that go on to produce stones or why those dogs do develop them. Much more information is required before any decisions can be reached on the breeding of carrier to carrier.
Animals excrete waste products in their urine. When most mammals metabolize compounds, called purines, they produce allantoin as one waste produce in their urine. Purines are natural substances found in all of the body's cells, and in virtually all foods. The reason for their widespread occurrence is simple: purines provide part of the chemical structure of our genes and the genes of plants and animals. Humans, great apes, and Dalmatian dogs produce a different break-down product, uric acid. This leads to high levels of uric acid in the urine and blood. In humans, this can result in diseases such as kidney stones and gout and may cause hypertension. In Dalmatians, and some affected Black Russian Terriers, high uric acid levels result in bladder stones that often have to be removed surgically. The cause of the high uric acid levels in humans and great apes is not the same as in the Dalmatian dog. When cells die and get recycled,the purines in their genetic material also get broken down. Uric acid is the chemical formed when purines have been broken down completely. Since our kidneys are responsible for helping keep blood levels of uric acid balanced, kidney problems can lead to excessive accumulation of uric acid in various parts of the body. Excessive break-down of cells can also cause uric acid build-up. In dogs predisposed to carry this genetic mutation the result will be uric acid stones.
Symptoms of Dog Bladder Stones
Frequent urination with small quantities
Bloody urine
Discomfort and straining while urinating
Dribbling urin (may indicate a
partial blockage of the urethra)
Urinating in inappropriate places.
Diagnosis
Ultrasounds are often performed to determine the size, shape and location of the stones. This will help your veterinarian to determine an appropriate treatment. Blood work will also be performed to determine if there are any underlying medical conditions causing the stones.
Treatment
Stones or sediment in the bladder can cause obstruction of the urinary pathway, i.e. blocking, which is basically the inability to urinate. This is much more likely to happen in males than females as males have a more restricted or constricted urinary track.
When a dog blocks, some form of veterinary intervention is required else the dog will progress to very painful and severe symptoms, including a burst bladder, likely to result in death. Blockage probably would never resolve itself un-treated. A simple procedure that sometimes works is called "back flushing" - inserting a catheter and forcing sterile liquid in an effort to move the stones back into the bladder. If that doesn't work, surgery becomes necessary. Usually this starts with cutting into the bladder and cleaning it out, often requiring incision of the urinary pathway as well (uresthrotomy).
"Sludge" in the bladder is often a pre-cursor to stones. This sludge is not harmless, as it forms clumps of concrete-like material which can also cause blockage, and is some-times more difficult to remove as it becomes enmeshed in the wall of the bladder.
In chronic cases, in males, to avoid the expense and pain of repeated surgery, there is a procedure to permanently re-route the urination tube so it no longer passes through the penis structure (uresthrostomy). Essentially this makes the males urinate like a female.
Prevention Hydration, Diet and Medication
Many breeders feel that risk of blockage can be greatly reduced by being sure the dogs drink plenty of water to dilute the UA in the urine. Low protein/purine diets are highly recommended.
The ideal diet for an affected dog would be low in purines (components of certain foods—primarily found in animal proteins—that metabolize into uric acid in the body), moderate in high-quality protein, high in complex carbohydrates (whole grains, fruits, and low—purine vegetables to help rid the body of extra uric acid), low in fat (fat holds onto uric acid in the kidneys), low in unnecessary fillers, and low in salt.
Low purine foods are: whole grain, yeast free breads and cereals, most vegetables, fruits, nuts, pasta, eggs, cheese, milk. Moderate purine foods would be: most poultry, fish and shellfish, lamb, and pork.
High purine foods which should be avoided with a dog prone to development or uric acid stones are: organ meats (kidneys, liver, brain, heart), game meats such as venison, duck and goose, sardines, mackerel, mussels and scallops and high purine vegetables such as cauliflower, spinach, peas, mushrooms and legumes, and brewer’s yeast.
There is a medication, Allopurinol, that is given commonly. In affected dogs, taking allopurinol is necessary for lifetime. Blockage still happens even when breeders make every effort to prevent it environmentally and nutritionally. In some cases, other life threatening health problems result from vegetarian low protein diets or from Allopurinol, which may cause xanthine stones.
Although Dalmatians are fixed for Hyperuricosuria, and the only way to remove the disease would be to introduce a group of experimental Dalmatians X Pointer backcross dogs into the breed gene pool to try to produce some Dalmatians' who do not carry the gene mutation, this is not true of the Black Russian Terrier. Therefore, genetic testing and selection in our breed can eliminate the disease, or at the very least keep it from becoming a greater problem than it already has. The next question is: are the breeders going to step up and start including genetic testing for Hyperuricosuria when analyzing a breeding pair?
Even if you are not interested in breeding your BRT, the information could provide you with valuable knowledge to be aware of the threat in your dog of the development of stones and to moderate his diet in an effort to try to prevent the stones from developing.
The test is inexpensive and easily obtained from UC Davis http://www.vgl.ucdavis.edu/ I would propose that it be included for CHIC
certification. Being a carrier will not eliminate any dog from the gene pool, since carriers are free of the disease symptoms, they can be freely crossed with dogs which have been DNA tested clear of the mutation, without producing any clinically affected pups. They can also be bred to another carrier with a 75% chance of producing only clear or carriers in their offspring. Careful breeding could eradicate effectively the disease from the Black Russian Terrier.
The one problem with the information provided by UC Davis concerning this genetic mutation is that they cannot provide any data on how many dogs carrying the double copy of the gene (affected dogs) will actually go on to produce dogs with urate stones. Some studies have indicated that there must also be another yet unidentified gene which actually causes the body to produce the stones when present with the currently identifed marker. From the large number of BRTs who are returning carrier and affected results there seems to be a much smaller percentage who actually develop a problem. Although the problem of stones does exist, it is not an extremely high percentage.
Their study has also only involved several breeds and does not indicate that there might not be many additional breeds who present with the genetic marker that they are testing for.
My opinion after a lot of reading is that while I would not breed an affected dog to a carrier, I also would not remove dogs from the gene pool based on the information we have to date, because there are still so many missing pieces to the research.
Copyright 2012 Midnight Rider Black Russian Terriers
Big word. Big problem.
Hyperuricosuria means elevated levels of uric acid in the urine. This will predispose dogs to form stones in their bladders and sometimes kidneys. There are several types of stones that can develop in dogs:
1. Struvite Bladder Stones –composed of magnesium, ammonium, and phosphate. More common in female dogs.
2. Calcium Oxalate Bladder Stones - These stones are formed in dogs that have a hereditary condition whereby they lack a calcium binding glycoprotein which inhibits the growth of calcium oxalate crystals in the urinary tract.
3. Uric Acid Bladder Stones - genetic in nature and caused because the liver cannot absorb uric acid.
The type of stones that we are concerned with here are the uric acid bladder stones.
Dalmatians are predominately affected by this disease. In fact, in Dalmatians only the mutant form of the identified gene (the SLC2A9)
occur, so all Dalmatians are affected and susceptible to urate bladder stones. In Black Russian Terriers and Bulldogs the disease is an autosomal recessive, which means that for a dog to be affected with the disease it must have two copies of the mu-tation in SLC2A9, one inherited from each parent.
The gene mutation was discovered by Dr. Danike Bannasch at the University of California (Davis). The complete research paper detailing the genetic identification and abnormality is available at: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000246. It is very detailed….much more than my intent to discuss here, but is interesting to read through.
Although Dalmatians are fixed for Hyperuricosuria (meaning all are affected), that is not the case in the Black Russian Terrier and Bulldog. We are still at the point where genetic testing and selection can eliminate the disease.
My interest in this started several years ago when I learned that UC Davis was conducting free testing on Black Russian Terriers. At that time I tested both of my dogs and found that Luba (Ebonies Pride Moya Lubov) is N/HU...a carrier of the mutation, but not affected. Best Guard Baikal (now deceased) was N/N ...clear of the mutation. Zil (Ch Zilya’s Chicago Blues Fusion at Runes), is N/HU, also a carrier but not affected.
The chart below shows the expected results when breeding nor-mal/carrier/affected dogs. As you can see, breeding normal males to normal females gives 100% normal puppies. Conversely breeding affected to affected will give 100% affected dogs with 2 copies of the genetic mutation that predisposes urate stone development. The breeding of two carriers will result in an expected 25% normal, 50% carriers, and 25% affected litter.
UC Davis has not yet published the frequencies of the mutation in Black Russian Terriers. From the very small sampling of owners who have wished to make their results public, it is fairly easy to see that this mutation is fairly common in the Black Russian Terrier and very careful breeding will be required to keep the BRT from becoming fixed with the mutation as is the Dalmatian. My problem with the studies currently is that there is no assurance that the genetic marker currently being used is really the one that indicates the likelihood of dogs forming stones. There are many, many affected (2 copies of the genetic marker) BRTs that show no problems or symptoms of stone formation. There has to be some other explanation of why only a small percentage of the affected dogs go on to produce stones. Either this is really a polygenic disease (as is hip dysplasia) where several genes have to combine to create the stone formation or there are environmental factors that cause an affected dog to form stones. The HU problem in the breed is a relatively new study and there are currently more unknows about the mechanics of stone formation than there are known factual information presented with studies to back it up. We all know of many instances where medical information was presented to the public (eat eggs/don't eat eggs, drink coffee/don't drink coffee, avoid alcohol/some alcohol is good) as dogma at the time of the initial study which has since been discredited or re-evaluated. UC Davis has not undertaken a long term study of the number of affected dogs that go on to produce stones or why those dogs do develop them. Much more information is required before any decisions can be reached on the breeding of carrier to carrier.
Animals excrete waste products in their urine. When most mammals metabolize compounds, called purines, they produce allantoin as one waste produce in their urine. Purines are natural substances found in all of the body's cells, and in virtually all foods. The reason for their widespread occurrence is simple: purines provide part of the chemical structure of our genes and the genes of plants and animals. Humans, great apes, and Dalmatian dogs produce a different break-down product, uric acid. This leads to high levels of uric acid in the urine and blood. In humans, this can result in diseases such as kidney stones and gout and may cause hypertension. In Dalmatians, and some affected Black Russian Terriers, high uric acid levels result in bladder stones that often have to be removed surgically. The cause of the high uric acid levels in humans and great apes is not the same as in the Dalmatian dog. When cells die and get recycled,the purines in their genetic material also get broken down. Uric acid is the chemical formed when purines have been broken down completely. Since our kidneys are responsible for helping keep blood levels of uric acid balanced, kidney problems can lead to excessive accumulation of uric acid in various parts of the body. Excessive break-down of cells can also cause uric acid build-up. In dogs predisposed to carry this genetic mutation the result will be uric acid stones.
Symptoms of Dog Bladder Stones
Frequent urination with small quantities
Bloody urine
Discomfort and straining while urinating
Dribbling urin (may indicate a
partial blockage of the urethra)
Urinating in inappropriate places.
Diagnosis
Ultrasounds are often performed to determine the size, shape and location of the stones. This will help your veterinarian to determine an appropriate treatment. Blood work will also be performed to determine if there are any underlying medical conditions causing the stones.
Treatment
Stones or sediment in the bladder can cause obstruction of the urinary pathway, i.e. blocking, which is basically the inability to urinate. This is much more likely to happen in males than females as males have a more restricted or constricted urinary track.
When a dog blocks, some form of veterinary intervention is required else the dog will progress to very painful and severe symptoms, including a burst bladder, likely to result in death. Blockage probably would never resolve itself un-treated. A simple procedure that sometimes works is called "back flushing" - inserting a catheter and forcing sterile liquid in an effort to move the stones back into the bladder. If that doesn't work, surgery becomes necessary. Usually this starts with cutting into the bladder and cleaning it out, often requiring incision of the urinary pathway as well (uresthrotomy).
"Sludge" in the bladder is often a pre-cursor to stones. This sludge is not harmless, as it forms clumps of concrete-like material which can also cause blockage, and is some-times more difficult to remove as it becomes enmeshed in the wall of the bladder.
In chronic cases, in males, to avoid the expense and pain of repeated surgery, there is a procedure to permanently re-route the urination tube so it no longer passes through the penis structure (uresthrostomy). Essentially this makes the males urinate like a female.
Prevention Hydration, Diet and Medication
Many breeders feel that risk of blockage can be greatly reduced by being sure the dogs drink plenty of water to dilute the UA in the urine. Low protein/purine diets are highly recommended.
The ideal diet for an affected dog would be low in purines (components of certain foods—primarily found in animal proteins—that metabolize into uric acid in the body), moderate in high-quality protein, high in complex carbohydrates (whole grains, fruits, and low—purine vegetables to help rid the body of extra uric acid), low in fat (fat holds onto uric acid in the kidneys), low in unnecessary fillers, and low in salt.
Low purine foods are: whole grain, yeast free breads and cereals, most vegetables, fruits, nuts, pasta, eggs, cheese, milk. Moderate purine foods would be: most poultry, fish and shellfish, lamb, and pork.
High purine foods which should be avoided with a dog prone to development or uric acid stones are: organ meats (kidneys, liver, brain, heart), game meats such as venison, duck and goose, sardines, mackerel, mussels and scallops and high purine vegetables such as cauliflower, spinach, peas, mushrooms and legumes, and brewer’s yeast.
There is a medication, Allopurinol, that is given commonly. In affected dogs, taking allopurinol is necessary for lifetime. Blockage still happens even when breeders make every effort to prevent it environmentally and nutritionally. In some cases, other life threatening health problems result from vegetarian low protein diets or from Allopurinol, which may cause xanthine stones.
Although Dalmatians are fixed for Hyperuricosuria, and the only way to remove the disease would be to introduce a group of experimental Dalmatians X Pointer backcross dogs into the breed gene pool to try to produce some Dalmatians' who do not carry the gene mutation, this is not true of the Black Russian Terrier. Therefore, genetic testing and selection in our breed can eliminate the disease, or at the very least keep it from becoming a greater problem than it already has. The next question is: are the breeders going to step up and start including genetic testing for Hyperuricosuria when analyzing a breeding pair?
Even if you are not interested in breeding your BRT, the information could provide you with valuable knowledge to be aware of the threat in your dog of the development of stones and to moderate his diet in an effort to try to prevent the stones from developing.
The test is inexpensive and easily obtained from UC Davis http://www.vgl.ucdavis.edu/ I would propose that it be included for CHIC
certification. Being a carrier will not eliminate any dog from the gene pool, since carriers are free of the disease symptoms, they can be freely crossed with dogs which have been DNA tested clear of the mutation, without producing any clinically affected pups. They can also be bred to another carrier with a 75% chance of producing only clear or carriers in their offspring. Careful breeding could eradicate effectively the disease from the Black Russian Terrier.
The one problem with the information provided by UC Davis concerning this genetic mutation is that they cannot provide any data on how many dogs carrying the double copy of the gene (affected dogs) will actually go on to produce dogs with urate stones. Some studies have indicated that there must also be another yet unidentified gene which actually causes the body to produce the stones when present with the currently identifed marker. From the large number of BRTs who are returning carrier and affected results there seems to be a much smaller percentage who actually develop a problem. Although the problem of stones does exist, it is not an extremely high percentage.
Their study has also only involved several breeds and does not indicate that there might not be many additional breeds who present with the genetic marker that they are testing for.
My opinion after a lot of reading is that while I would not breed an affected dog to a carrier, I also would not remove dogs from the gene pool based on the information we have to date, because there are still so many missing pieces to the research.
Copyright 2012 Midnight Rider Black Russian Terriers
|
N/N (NORMAL)
|
N/HU (CARRIER)
|
HU/HU AFFECTED
|
|
N/N (NORMAL)
|
100% OF LITTER WILL BE N/N
|
50% OF LITTER MAY BE N/N
50% OF LITTER MAY BE N/HU |
100% OF LITTER WILL BE N/HU
|
|
N/HU (CARRIER)
|
50% OF LITTER MAY BE N/N
50% OF LITTER MAY BE N/HU |
25% OF LITTER MAY BE N/N
50% OF LITTER MAY BE N/HU 25% OF LITTER MAY BE HU/HU |
50% OF LITTER MAY BE N/HU
50% OF LITTER MAY BE HU/HU |
|
HU/HU (AFFECTED)
|
100% OF LITTER WILL BE N/HU
|
50% OF LITTER MAY BE N/HU
50% OF LITTER MAY BE HU/HU |
100% OF LITTER WILL BE HU/HU
|