Pathological correlations between podocyte injuries and renal functions in canine and feline chronic kidney diseases
Osamu Ichii1, Akira Yabuki2, Nobuya Sasaki3, Saori Otsuka1, Hiroshi Ohta4, Masahiro Yamasaki4, Mitsuyoshi Takiguchi4, Yuka Namiki5, Yoshiharu Hashimoto5, Daiji Endoh6 and Yasuhiro Kon1
1Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan, 2Laboratory of Clinical Pathology, Department of Veterinary Sciences, Kagoshima University, Kagoshima, Japan, 3Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan, 4Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan, 5Office for Faculty Development and Teaching Enriched Veterinary Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan and 6Department of Veterinary Radiology, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Ebetsu, Japan.
Offprint requests to: Osamu Ichii DVM, PhD, Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18-Nishi 9, Kita-ku, Sapporo 060-0818, Japan. e-mail: firstname.lastname@example.org
Summary. Podocytes cover the glomerulus and their adjacent foot processes form a principal barrier called the slit diaphragm. Podocyte dysfunctions, including podocyte loss and slit diaphragm disruptions, induce chronic kidney diseases (CKD). In this study, we analyzed the correlations between podocyte injuries and renal dysfunctions in domestic carnivores. Dogs and cats were divided into normal and CKD groups according to renal histopathology and plasma creatinine values. Immunostaining results showed that linear reactions of slit diaphragm molecules, e.g., nephrin, podocin, and ACTN4, were parallel to glomerular capillaries in all animals. However, in dogs, reactions of nephrin and ACTN4 were changed to a granular pattern in the CKD group, and their intensities significantly decreased with the number of podocytes in the glomerulus. Moreover, the expression of nephrin and ACTN4 negatively correlated with creatinine. Real-time PCR analysis showed that nephrin mRNA expression in the kidneys of CKD dogs was significantly lower than that in normal animals, and negatively correlated with creatinine. Although no significant correlation between renal dysfunction and podocyte injury was detected in cats, histoplanimetric scores of tubulointerstitial lesions in CKD cats were higher than those in both normal cats and diseased dogs. Furthermore, mRNAs of WT1 and SD molecules were detected in urine from CKD animals. In conclusion, podocyte injuries such as podocytopenia and decreased expression of nephrin and ACTN4 in the glomerulus were more strongly correlated with renal dysfunction in dogs than in cats. These findings suggest that the CKD pathogenesis, especially susceptibilities to podocyte injuries, differed between dogs and cats. Histol Histopathol 26, 1243-1255 (2011)
Key words: CKD, Podocyte, Dog, Cat