Colony Dogs Update — July 2009
Shelly Vaden DVM PhD — North Carolina State University
Fifteen years ago, the first dogs were born into our colony. The dogs have been wonderful! They have provided us with great joy as well as a wealth of information. These dogs were bred with several goals in mind. It is time to reflect on what we have accomplished.
The first goal was to determine the mode of inheritance (MOI) of this disorder. In order to do this, one of our male dogs was bred to a Beagle to create Wheagles. These dogs were then sequentially evaluated over time. Some of the Wheagles developed overt disease. This would suggest that the disease is inherited as a dominant trait. However, the prevalence of disease within the colony of purebred dogs is high, supportive of an autosomal recessive mode of inheritance (MOI). Determination of the exact mode of inheritance (MOI) may require a second outcross breeding to a dog of a breed other than a SCWT or a Beagle. At this point in time, we cannot say with certainty that Beagles do not have a similar abnormality that is complicating the phenotypic expression of PLE and PLN in our Wheagles. DNA has been harvested from all of our dogs, and we have supplied any interested researcher with this DNA in hope of facilitating the identification of a genetic marker. Once a genetic marker for this disease is discovered, we most likely will be able to confirm the mode of inheritance (MOI) through application of the marker.
Our second goal was to sequentially evaluate dogs to gain a better understanding of the development of clinical signs of this disease, so that we could make better recommendations for screening SCWTs. We have been able to effectively achieve this goal. We know that increases in fecal API are prevalent throughout the colony (and the general population of SCWTs). These precede the onset of PLE. However, overt PLE, as manifested by decreased serum protein concentrations, does not always precede the onset of PLN. The dogs developing overt PLE have had a greater number of fecal API samples >18.7 ug/g. All affected dogs that have been tested have had enteric food allergies. This information is very useful because it suggests that the enteric disease may have a pathogenic role in the renal disease, as suspected. In order to be an effective screening tool, evaluation of fecal API must be initiated in dogs that are less than 3 years of age and continued annually lifelong. As for PLN, we found that microalbuminuria is highly prevalent in SCWTs of our colony. It often precedes the onset of increased urine protein:creatinine ratios, which is a standard test used to screen dogs for proteinuria. Some dogs of our colony had sporadic microalbuminuria, and some have increased values that are not progressively increasing. However, we know that microalbuminuria that is persistent and of increasing magnitude is the best early predictor of PLN.
We have also been evaluating the therapeutic benefit of sodium cromoglycate administration and hydrolysate diet consumption in the affected SCWTs of our colony. This has been a more difficult study to perform because our other objectives require that we follow the disease to a later stage than which we might generally intervene therapeutically by today's standards. Even in this later stage of disease, there does appear to be some benefit of the therapies in certain dogs. However, some individual dogs have not responded. Some dogs also have responded to the administration of an elemental diet (Vivonex). In clinically affected dogs, providing an elemental diet may give the intestinal tract a period of relative rest, allowing it to regain some function and start to recover. Perhaps this period of rest will give time for other therapeutic agents (e.g., corticosteroids) to be more effective.
As a final part of these studies, we have been feeding a litter of dogs a hydrolysate diet since weaning. It appears that this diet may delay the onset of PLE or at least make the clinical manifestations of it less severe. However, 2 of these 4 dogs have succumbed to PLN. This data is preliminary, because 2 of the dogs are still alive. Absolute conclusions cannot be made at this time. Furthermore, direct applications of these findings to the general population of dogs will be difficult. We are certainly not advising that apparently unaffected SCWTs from the general population be fed a hydrolysate diet.
We have been blessed with 22 dogs: 14 SCWTs and 8 SCWTxBeagles (Wheagles). So how many are still with us? We only have 2 SCWT and 5 SCWTxBeagles (Wheagles) remaining. Of the 2 SCWTs, one has PLE and the other does not have any clinically apparent disease. The 8 SCWTxBeagles (Wheagles) will be 14 years old this October. We are starting to see some geriatric diseases in them that are not related to PLE/PLN. Many of them have mild osteoarthritis. One had a stroke and a rectal tumor but is still living the good life. Two of them have proteinuria that may be unrelated to the disease we are studying. One has PLE/PLN. All dogs appear to still enjoy their daily routine and are free of persistent symptoms.
We are always open to collaborative studies and have many samples that can be shared. To date we have collaborated with investigators from the GI Lab at Texas A&M University, Karin Allenspach of the Royal Veterinary College, Iwan Burgener and other investigators from Bern University, Meryl Littman and Paula Henthorn at Penn, and investigators in the Clinical Nutrition group at NCSU.