Abstract
Two articles provide information about the recent pet food contamination with melamine and cyanuric acid and their effects in cats and dogs. The report by Brown et al. describes histopathologic features in kidneys of 14 cats and dogs involved in the 2007 outbreak and compares these findings with a lesser known outbreak involving two dogs in 2004. Renal lesions included variable numbers of light green to slightly basophilic polarizable crystals in distal tubules and/or collecting ducts. The crystals were round with radiating striations, or small globular aggregates. The crystals can be distinguished from oxalate crystals by their morphology and the fact that oxalate crystals are predominantly found in the proximal tubules. The manuscript by Puschner et al. describes the acute nephrotoxic effects of feeding melamine in combination with cyanuric acid, whereas each compound alone was not associated with altered renal function. As described by Brown et al., kidneys of cats fed the combination had numerous birefringent crystals in the distal tubules and collecting ducts, with sparing of the proximal tubules. It is speculated that renal damage may be due in part to intratubular precipitation and subsequent acute intrarenal obstruction. It should be noted that crystals may dissolve with prolonged formalin fixation.
Brown CA, Jeong K-S, Poppenga RH, et al. Outbreaks of renal failure associated with melamine and cyanuric acid in dogs and cats in 2004 and 2007. J Vet Diagn Invest 19(5):525–531, 2007. Puschner B, Poppenga RH, Lowenstine LJ, Filigenzi MS, Pesavento PA. Assessment of melamine and cyanuric acid toxicity in cats. J Vet Diagn Invest
New research sheds light on the mechanism of development of polycystic kidney disease. Mutations in PKD1 are responsible for polycystic kidney disease in humans and cats, but it is uncertain whether cysts continue to form throughout life or if cystogenesis is restricted to development and early childhood. Using a Pkd1 conditional knockout mouse, Piontek and colleagues show that inactivation of Pkd1 before postnatal day 13 results in severely cystic kidneys within three weeks. This is in contrast to inactivation at day 14 or later, which results in cyst formation after the mice reach five months of age. The authors found that the abrupt change in response to Pkd1 inactivation corresponds to a brake point in renal tissue growth and marked changes in gene expression patterns, indicating that a developmental switch coinciding with Pkd1 inactivation signals the end of renal maturation.
Piontek K, Menezes LF, Garcia-Gonzalez MA, Huso DL, Germino GG. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med
Intraepithelial lesions (IELs) such as atypical hyperplasia and ductal carcinoma in situ (DCIS) are common findings in breast biopsies from women. The authors of this study analyzed mammary tumors from 200 dogs to determine if the canine is an appropriate model for IELs in women, particularly those with estrogen receptor (ER)-negative lesions. Sixty dogs (30%) had mammary IELs and these bore a striking resemblance to the corresponding human histologies. Canine DCIS was strongly associated with malignant tumors, and it is known that DCIS in humans carries a high relative risk for invasive carcinoma. The majority of canine DCIS lesions had a very low percentage (0-5%) of ER-positive cells, and two thirds of high grade DCIS were positive for HER-2 expression based on immunohistochemical staining. Together these results demonstrate that further investigation of canine IELs as a model for humans is clearly warranted, and dogs could play an important role in evaluation of prevention strategies and novel therapeutics.
Antuofermo E, Miller MA, Pirino S, Xie J, Badve S, Mohammed SI. Spontaneous mammary intraepithelial lesions in dogs – a model of breast cancer. Cancer Epidemiol Biomarkers Prev
Tibial dyschondroplasia is seen in rapidly growing birds and is characterized by a focus of avascular cartilage in the proximal metaphysis of the tibiotarsus and tarsometatarsus. The mechanism of formation of the avascular plug is not known, but abnormal angiogenesis has been proposed. The authors of this study examined various molecules involved in angiogenic signaling to determine if these were disrupted during the development of tibial dyschondroplasia in chickens. Vascular endothelial growth factor (VEGF), VEGF receptor Flk-1, matrix metalloproteinase (MMP)-9 and MMP-13 were evaluated by immunohistochemistry. Rachitic tissues from vitamin-D deficient chicks were also examined. The authors found that all gene products were present in normal and diseased cartilage, with only minor differences in distribution and staining intensity. While actual angiogenesis was not evaluated, this study indicates that expression of these angiogenic-related factors is not altered in tibial dyschondroplasia or rachitic cartilage in chickens.
Gay CV, Gilman VR, Leach RM. Immunolocalization of vascularization factors in normal, tibial dyschondroplasia and rachitic cartilage. Avian Pathol