Frequently Asked Questions about Boxer JKD
BoxerJKD has been called other names - is it all the same disease?
The scientific name for JKD - 'Juvenile Kidney Disease' in Boxers the disease has had several
proposed names - reflux nephropathy with segmental hypoplasia or Progressive/Juvenile
Nephropathy (PNP), the disease falls under the umbrella of a Renal Dysplasia. Renal Dyplasia is when the kidneys do not develop correctly during gestation. In Boxers the disease appears to
be different from dyplasias that have been identified in other breeds. All dyplasias so far identified appear to have differing inheritances - and appear to be caused by different genes - some recessive some dominant. The word Juvenile is only used to show that the dogs are born with the condition as it happens during gestation - it does not
mean that the dogs will only develop the condition as a Juvenile - many cases are diagnosed later in
life. The term JKD was being used several years ago in the UK - boxerJKD did contemplate using the
other names but as JKD was already in common usage - there did not seem a reason to confuse
things further by changing the name. Sweden has already dropped the Juvenile completely.
The scientific name for JKD - 'Juvenile Kidney Disease' in Boxers the disease has had several
proposed names - reflux nephropathy with segmental hypoplasia or Progressive/Juvenile
Nephropathy (PNP), the disease falls under the umbrella of a Renal Dysplasia. Renal Dyplasia is when the kidneys do not develop correctly during gestation. In Boxers the disease appears to
be different from dyplasias that have been identified in other breeds. All dyplasias so far identified appear to have differing inheritances - and appear to be caused by different genes - some recessive some dominant. The word Juvenile is only used to show that the dogs are born with the condition as it happens during gestation - it does not
mean that the dogs will only develop the condition as a Juvenile - many cases are diagnosed later in
life. The term JKD was being used several years ago in the UK - boxerJKD did contemplate using the
other names but as JKD was already in common usage - there did not seem a reason to confuse
things further by changing the name. Sweden has already dropped the Juvenile completely.
What is a really simple explanation of BoxerJKD?
JKD - simple definition - a developmental familial chronic kidney disease in Boxers. Diagnosed by vets when all other known causes have been excluded, other causes of kidney disease could be secondary to other diseases, various infections, several different parasites, some toxins etc. etc. . Ultra Sound of such dogs has often shown poorly developed kidneys. Kidneys develop in the womb and in the first few weeks of life - these dogs do not appear to develop normal kidneys. These abnormal kidneys do not produce and clear the urine normally - they fail to concentrate
the urine and suffer from a 'reflux action' inside the kidney- this leaves the dogs vulnerable to infections and subsequently further secondary changes to the kidney. The disease is progressive. By the time the dog has died - and IF the kidneys are harvested for a Post mortem - the primary reasons why the kidney did not function correctly in the first place could of been lost in some individuals. The damage in many kidneys by the time of death is extensive. Post Mortems can therefore be inconclusive due to the inability to identify the primary causes. The primary cause is what the gene test is aimed at – this is the genetic aspect of the disease - not the secondary disease processes that take place as the disease progresses.
From the Merck Manual
Specific renal function tests and renal biopsy may be helpful to identify the exact cause in Stages 1–3, but the presence of advanced pathologic changes in Stage 4 is nonspecific and often precludes identification of an underlying cause by histologic studies. This condition in late Stage 4 is often described as end-stage renal failure clinically and as chronic, generalized nephritis pathologically.
JKD - simple definition - a developmental familial chronic kidney disease in Boxers. Diagnosed by vets when all other known causes have been excluded, other causes of kidney disease could be secondary to other diseases, various infections, several different parasites, some toxins etc. etc. . Ultra Sound of such dogs has often shown poorly developed kidneys. Kidneys develop in the womb and in the first few weeks of life - these dogs do not appear to develop normal kidneys. These abnormal kidneys do not produce and clear the urine normally - they fail to concentrate
the urine and suffer from a 'reflux action' inside the kidney- this leaves the dogs vulnerable to infections and subsequently further secondary changes to the kidney. The disease is progressive. By the time the dog has died - and IF the kidneys are harvested for a Post mortem - the primary reasons why the kidney did not function correctly in the first place could of been lost in some individuals. The damage in many kidneys by the time of death is extensive. Post Mortems can therefore be inconclusive due to the inability to identify the primary causes. The primary cause is what the gene test is aimed at – this is the genetic aspect of the disease - not the secondary disease processes that take place as the disease progresses.
From the Merck Manual
Specific renal function tests and renal biopsy may be helpful to identify the exact cause in Stages 1–3, but the presence of advanced pathologic changes in Stage 4 is nonspecific and often precludes identification of an underlying cause by histologic studies. This condition in late Stage 4 is often described as end-stage renal failure clinically and as chronic, generalized nephritis pathologically.
What does Juvenile mean in BoxerJKD - does it mean that it only effects young dogs?
Juvenile means that the disease starts during the development of the puppy, it means that the kidneys did not develop properly. Many cases of BoxerJKD are picked up in young puppies and dogs but many more cases do not get identified till much later. Often bitches develop symptoms after or during pregnancy.
Juvenile means that the disease starts during the development of the puppy, it means that the kidneys did not develop properly. Many cases of BoxerJKD are picked up in young puppies and dogs but many more cases do not get identified till much later. Often bitches develop symptoms after or during pregnancy.
Are all reported cases of BoxerJKD in the UK confirmed? How do we know that this is really JKD?
How about substituting the word Unexplained for your insistence of using the word confirmed - see how that sits - then we have many boxers dying of unexplained kidney disease. The interesting thing is that all these dogs are related - the only connection between these unexplained chronic kidney failures is their shared genetics and family history. So we now have a familial inherited ‘unexplained’ kidney disease that kills Boxers
How about substituting the word Unexplained for your insistence of using the word confirmed - see how that sits - then we have many boxers dying of unexplained kidney disease. The interesting thing is that all these dogs are related - the only connection between these unexplained chronic kidney failures is their shared genetics and family history. So we now have a familial inherited ‘unexplained’ kidney disease that kills Boxers
How can we be sure that this is a genetic disease - we know so little about the disease?
Just because a disease has not been adequately defined does not mean that it is in anyway
misunderstood. Many many diseases both in human and animal species will never be fully defined.
Not many of the genes that cause any of the genetic disease have ever been identified - that does
not mean that the disease is not inherited – or that it cannot be controlled. The chances of closely
related dogs from all over the world all developing a developmental chronic kidney disease is minute
Just because a disease has not been adequately defined does not mean that it is in anyway
misunderstood. Many many diseases both in human and animal species will never be fully defined.
Not many of the genes that cause any of the genetic disease have ever been identified - that does
not mean that the disease is not inherited – or that it cannot be controlled. The chances of closely
related dogs from all over the world all developing a developmental chronic kidney disease is minute
How useful is USG testing - what do you recommend?
USG screening is all about trying to identify sub clinical cases that have a reduced renal function - all puppies bred should be tested from 4 months on - maybe every couple of months - if the USG is below 1.030 then the tests need to be repeated, any dog consistently having low readings or readings of 1.020 and below is suspicious and should be investigated in depth - then keeping a check on all the breeding adults - screening any dog intended for future
breeding – holding off breeding till 3 years old might also help - as JKD is a progressive disease - USG screening picks up dogs unable to concentrate their urine. USG screening will not pick up carriers of the genes but will help identify producers of the disease - so if all possible JKD cases are identified by their breeders then this information can be used to prevent further matings of sub clinical dogs or producers. USG screening will not identify carriers - but will identify cases and might identify sub clinical (homozygotes), then once these are identified you have identified the producers
USG screening will identify dogs with insufficient renal function - these will be either dogs before the disease progresses to kidney failure or dogs that will never progress to kidney failure – either way the genetics will still be there - so identifying them and removing them and maybe the immediate siblings and parents from breeding will reduce the incidence of the disease and in time will reduce the frequency of the gene in the population
USG screening is all about trying to identify sub clinical cases that have a reduced renal function - all puppies bred should be tested from 4 months on - maybe every couple of months - if the USG is below 1.030 then the tests need to be repeated, any dog consistently having low readings or readings of 1.020 and below is suspicious and should be investigated in depth - then keeping a check on all the breeding adults - screening any dog intended for future
breeding – holding off breeding till 3 years old might also help - as JKD is a progressive disease - USG screening picks up dogs unable to concentrate their urine. USG screening will not pick up carriers of the genes but will help identify producers of the disease - so if all possible JKD cases are identified by their breeders then this information can be used to prevent further matings of sub clinical dogs or producers. USG screening will not identify carriers - but will identify cases and might identify sub clinical (homozygotes), then once these are identified you have identified the producers
USG screening will identify dogs with insufficient renal function - these will be either dogs before the disease progresses to kidney failure or dogs that will never progress to kidney failure – either way the genetics will still be there - so identifying them and removing them and maybe the immediate siblings and parents from breeding will reduce the incidence of the disease and in time will reduce the frequency of the gene in the population
Can infections such as Ecoli cause JKD?
E.coli is just an opportunistic infection. Kidneys with the JKD defect do not clear the urine from the kidneys - this sort of backs up - called reflux, this then increases the risk of UTI infections - the UTIs do not cause the primary kidney defect, repeated UTIs will cause the disease to progress more quickly - the kidney suffers further secondary damage - scarring, fibrosis tissues, cysts, tubule destruction etc. - it is progressive - hence the many different scientific disease names given to it already – progressive/juvenile nephropathy, reflux nephropathy with segmented hypoplasia etc. etc. This is what the UK kidney specialist is itching to do - BoxerJKD is not a simple renal dysplasia - it falls under the umbrella of a dysplasia but will be unique from other known dysplasias
E.coli is just an opportunistic infection. Kidneys with the JKD defect do not clear the urine from the kidneys - this sort of backs up - called reflux, this then increases the risk of UTI infections - the UTIs do not cause the primary kidney defect, repeated UTIs will cause the disease to progress more quickly - the kidney suffers further secondary damage - scarring, fibrosis tissues, cysts, tubule destruction etc. - it is progressive - hence the many different scientific disease names given to it already – progressive/juvenile nephropathy, reflux nephropathy with segmented hypoplasia etc. etc. This is what the UK kidney specialist is itching to do - BoxerJKD is not a simple renal dysplasia - it falls under the umbrella of a dysplasia but will be unique from other known dysplasias
Do UTI's cause the development of JKD? Why is JKD more common in bitches?
Urinary tract infections are NOT a cause of JKD, but are a consequence of the disease and the malformed kidney structure. The kidneys do not clear the urine efficiently, the urine can reflux and make the urine tract prone to infection. These infections can ascend the ureters and cause damage to the kidney themselves. Persistent and frequent UTIs in a dog can aid detection of JKD.
The urinary tract in bitches is much shorter than that of dogs and therefore their kidneys are at greater risk of infection. This is one reason why JKD is seen more frequently in bitches compared to dogs. Bitches will often be put under the stress of pregnancy - this can cause the onset of symptoms as BoxerJKD kidneys can not cope with the added physiological stresses caused by pregnancy
Urinary tract infections are NOT a cause of JKD, but are a consequence of the disease and the malformed kidney structure. The kidneys do not clear the urine efficiently, the urine can reflux and make the urine tract prone to infection. These infections can ascend the ureters and cause damage to the kidney themselves. Persistent and frequent UTIs in a dog can aid detection of JKD.
The urinary tract in bitches is much shorter than that of dogs and therefore their kidneys are at greater risk of infection. This is one reason why JKD is seen more frequently in bitches compared to dogs. Bitches will often be put under the stress of pregnancy - this can cause the onset of symptoms as BoxerJKD kidneys can not cope with the added physiological stresses caused by pregnancy
Do all dogs with BoxerJKD have smaller kidneys on Ultrasound?
Most BoxerJKD cases can be confirmed by ultrasound as they have smaller odd shaped kidneys. But some cases that appeared normal by ultrasound proved to have JKD under post mortem examination.
While malformed, scarred, or even a missing kidney may be observed with ultrasound, a failure to observe such does NOT mean that the kidneys are functionally normal.
Most BoxerJKD cases can be confirmed by ultrasound as they have smaller odd shaped kidneys. But some cases that appeared normal by ultrasound proved to have JKD under post mortem examination.
While malformed, scarred, or even a missing kidney may be observed with ultrasound, a failure to observe such does NOT mean that the kidneys are functionally normal.
Does Post Mortem always prove a diagnosis of BoxerJKD?
Histopathology of kidney samples from post mortem samples of kidney tissue are looking for the presence of juvenile undifferentiated tissues such as undifferentiated mesenchyme, primitive ducts, primitive glomeruli. The presence of these cells will prove a diagnosis of Renal Dysplasia. The absence of these cells does not disprove the diagnosis of BoxerJKD. Due to the progressive nature of BoxerJKD sometimes the kidneys are so badly damaged by the secondary disease processes that the primary lesions and juvenile cell types can not be found. Another reason is that the sample taken did not contain these cell types.
While the detection of immature cells on kidney histo-pathology is taken to be the key diagnostic evidence for what is defined as renal dysplasia(RD), failure to detect these cells does NOT refute an RD diagnosis. The pathology uses only samples of kidneys; the immature cells of even affected regions of the kidney may be missed. Alternatively, the kidneys may be too damaged by the disease process for critical analysis to find these cells.
From the section in the Merck Manual by the time that many dogs have entered into Stage 4 kidney failure the undifferentiated tissues will most likely impossible to find it states.
Histopathology of kidney samples from post mortem samples of kidney tissue are looking for the presence of juvenile undifferentiated tissues such as undifferentiated mesenchyme, primitive ducts, primitive glomeruli. The presence of these cells will prove a diagnosis of Renal Dysplasia. The absence of these cells does not disprove the diagnosis of BoxerJKD. Due to the progressive nature of BoxerJKD sometimes the kidneys are so badly damaged by the secondary disease processes that the primary lesions and juvenile cell types can not be found. Another reason is that the sample taken did not contain these cell types.
While the detection of immature cells on kidney histo-pathology is taken to be the key diagnostic evidence for what is defined as renal dysplasia(RD), failure to detect these cells does NOT refute an RD diagnosis. The pathology uses only samples of kidneys; the immature cells of even affected regions of the kidney may be missed. Alternatively, the kidneys may be too damaged by the disease process for critical analysis to find these cells.
From the section in the Merck Manual by the time that many dogs have entered into Stage 4 kidney failure the undifferentiated tissues will most likely impossible to find it states.
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Specific renal function tests and renal biopsy may be helpful to identify the exact cause in Stages 1–3, but the presence of advanced pathologic changes in Stage 4 is nonspecific and often precludes identification of an underlying cause by histologic studies. This condition in late Stage 4 is often described as end-stage renal failure clinically and as chronic, generalized nephritis pathologically.
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Can we just stop breeding from dogs that have carriers in the pedigree?
A decision was made by BoxerJKD team early on not to report any cases earlier than 10 years ago. The disease has been with the breed for a very long time and it was not thought to be beneficial to look back too far as it is the current dogs that are important to the future of the breed. We also decided not to comment on the potential line of inheritance of the disease within the published pedigrees. A pedigree study easily identifies the common ancestors. Only producers of confirmed cases of BoxerJKD are shaded in blue. It is worth noting that many dogs in the published pedigrees could be shaded as being deduced carriers or as siblings to cases or other confirmed JKD carriers. So a dog being unshaded in a published pedigree does not mean it is completely without risk.
The gene responsible for JKD is widespread and appears in almost all of the current breeding lines in the UK. There will be 'clear' dogs in those lines too. We just need to reduce the risk of using the sub clinical and carrier dogs and increase the chance of breeding to the clear dogs.
To preserve the genetic diversity you can not simply exclude all dogs with carriers or deduced carriers in their pedigrees.
To decrease the current risks, it is suggested that breeders screen all their stock for low USG readings, reduce the inbreeding in their planned litters, not to double up on pedigrees containing carriers.
Any new cases of JKD found by the screening process needs to be reported and the information shared with other breeders, the parents of all JKD cases need to be immediately removed from breeding programmes.
For the overall genetic health of the breed, breeders need to use as many different stud dogs as possible rather than giving only one or two dogs all the stud work nationally. A 'popular sire' effect can be very detrimental to the genetic health of the breed in more ways than just the risks of JKD.
If breeders become more acceptable to the recommendations and problems of BoxerJKD, then we may consider publication of the deduced carriers and full JKD inheritance history. But in the current climate it is hard to see the benefit of doing this.
The solution to the problem is working with the current dogs, having an efficient USG screening programme of all puppies and breeding stock, together with the effective sharing of all of the available information with all Boxer breeders worldwide.
Unfortunately, there is still much more to do, as only the pedigrees that have been shared to BoxerJKD team are available in the public domain. This is still is not the full current available picture. The incidence of JKD is relatively low due to the low penetrance and the over capacity of the kidneys. It is therefore extremely important that all BoxerJKD cases should be reported and the pedigree information shared. Too many cases are being lost to the study for many different and diverse reasons. But the open reporting and the sharing of all available pedigree information is fundamental to continuing to reduce the frequency of the JKD gene within the population.
A decision was made by BoxerJKD team early on not to report any cases earlier than 10 years ago. The disease has been with the breed for a very long time and it was not thought to be beneficial to look back too far as it is the current dogs that are important to the future of the breed. We also decided not to comment on the potential line of inheritance of the disease within the published pedigrees. A pedigree study easily identifies the common ancestors. Only producers of confirmed cases of BoxerJKD are shaded in blue. It is worth noting that many dogs in the published pedigrees could be shaded as being deduced carriers or as siblings to cases or other confirmed JKD carriers. So a dog being unshaded in a published pedigree does not mean it is completely without risk.
The gene responsible for JKD is widespread and appears in almost all of the current breeding lines in the UK. There will be 'clear' dogs in those lines too. We just need to reduce the risk of using the sub clinical and carrier dogs and increase the chance of breeding to the clear dogs.
To preserve the genetic diversity you can not simply exclude all dogs with carriers or deduced carriers in their pedigrees.
To decrease the current risks, it is suggested that breeders screen all their stock for low USG readings, reduce the inbreeding in their planned litters, not to double up on pedigrees containing carriers.
Any new cases of JKD found by the screening process needs to be reported and the information shared with other breeders, the parents of all JKD cases need to be immediately removed from breeding programmes.
For the overall genetic health of the breed, breeders need to use as many different stud dogs as possible rather than giving only one or two dogs all the stud work nationally. A 'popular sire' effect can be very detrimental to the genetic health of the breed in more ways than just the risks of JKD.
If breeders become more acceptable to the recommendations and problems of BoxerJKD, then we may consider publication of the deduced carriers and full JKD inheritance history. But in the current climate it is hard to see the benefit of doing this.
The solution to the problem is working with the current dogs, having an efficient USG screening programme of all puppies and breeding stock, together with the effective sharing of all of the available information with all Boxer breeders worldwide.
Unfortunately, there is still much more to do, as only the pedigrees that have been shared to BoxerJKD team are available in the public domain. This is still is not the full current available picture. The incidence of JKD is relatively low due to the low penetrance and the over capacity of the kidneys. It is therefore extremely important that all BoxerJKD cases should be reported and the pedigree information shared. Too many cases are being lost to the study for many different and diverse reasons. But the open reporting and the sharing of all available pedigree information is fundamental to continuing to reduce the frequency of the JKD gene within the population.
