Familial renal disease in soft-coated wheaten terriers

To review what is known about the familial renal diseases in soft-coated wheaten terriers (SCWT), provide an update in developments in this field including the relationship with protein-losing nephropathy (PLN) and the potential association with protein-losing enteropathy (PLE).

Information was derived from studies of dogs maintained in the North Carolina State University colony, information contained within an open registry of affected dogs, and data gathered from the general population of wheaten terriers at risk as well as studies performed on banked DNA samples from affected SCWT in the general population and normal geriatric dogs seen at the University of Pennsylvania (PennVet).

A two-hit pathogenesis has been proposed in some types of human focal segmental glomerulosclerosis, specifically the subset of cases that are associated with a podocytopathy. At risk podocytes may be predisposed to injury by disease processes that would be reversible in other patients.

Mutations were found in association with PLN in SCWT, indicating a podocytopathy that causes a change in glomerular permselectivity. This podocytopathy leads to the development of lesions resembling focal segmental glomerulosclerosis. There is also strong evidence supporting a high prevalence of food hypersensitivity reactions in SCWT, although it is unclear if these reactions have a primary or secondary role in the development of PLE. There are also suggestions of immunodysregulation in affected SCWT.

PLN in SCWT is due to a podocytopathy. The cause of PLE has not been identified; however, it is possible that PLE develops from a functional-structural abnormality in the intestines and food allergies develop as secondary phenomena. It is also possible that inflammatory events that are the result of either immunodysregulation or food allergies might lead to the development of PLE. In either case, PLE most likely exacerbates PLN in affected SCWT.