title: Progression of renal fibrosis in congenital CKD model rats with reduced number of nephrons.
abstract: A congenital reduction in the number of nephrons is a critical risk factor for both onset of chronic kidney disease (CKD) and its progression to end-stage kidney disease (ESKD). Hypoplastic kidney (HPK) rats have only about 20% of the normal number of nephrons and show progressive CKD. This study used an immunohistological method to assess glomerular and interstitial pathogenesis in male HPK rats aged 35-210days. CD68 positive-macrophages were found to infiltrate into glomeruli in HPK rats aged 35 and 70days and to infiltrate into interstitial tissue in rats aged 140 and 210days. HPK rats aged 35 and 70days showed glomerular hypertrophy, loss of normal linear immunostaining of podocine, and increased expression of PDGFr-β, TGF-β, collagens, and fibronectin, with all of these alterations gradually deteriorating with age. α-SMA-positive myofibroblasts were rarely detected in glomerular tufts, whereas α-SMA-positive glomerular parietal epithelium (GPE) cells were frequently observed along Bowman's capsular walls. The numbers of PDGFr-β-positive fibroblasts in interstitial tissue were increased in rats aged 35days and older, whereas interstitial fibrosis, characterized by the increased expression of tubular PDGF-BB, the appearance of myofibroblasts doubly positive for PDGFr-β and α-SMA, and increased expression of collagens and fibronectin, were observed in rats aged 70 and older. These results clearly indicate that congenital CKD with only 20% of nephrons cause renal fibrosis in rats.
authors.affiliation: Laboratory of Veterinary Physiology, Unit of Functional Morphology, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yasuda
authors.affiliation: Laboratory of Veterinary Physiology, Unit of Functional Morphology, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tochigi
authors.affiliation: Laboratory of Veterinary Physiology, Unit of Functional Morphology, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Katayama
authors.affiliation: Laboratory of Veterinary Physiology, Unit of Functional Morphology, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan. Electronic address: hiroetsu@nvlu.ac.jp.
authors.forename: Hiroetsu
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis / Q000473:pathology; D008297:Male; D009399:Nephrons / Q000473:pathology; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000151:congenital* / Q000473:pathology*
keywords: Chronic kidney disease; Glomerulosclerosis; Interstitial fibrosis; Myofibroblasts; Renal hypoplasia