Hood Jennifer C, Dowling John, Bertram John F, Young Richard J, Huxtable Clive, Robinson Wayne, Savige Judy
Section of Pathology, Division of Veterinary and Biomedical Sciences, Murdoch University, Western Australia, Australia.
Nephrol Dial Transplant. 2002 Nov;17(11):1897-908. doi: 10.1093/ndt/17.11.1897.
Bull terrier hereditary nephritis represents a model for autosomal dominant Alport syndrome, as affected dogs have the characteristically lamellated glomerular basement membrane and demonstrate vertical male-to-male disease transmission.
This study compared the histopathological features in kidneys from affected Bull terrier neonates, puppies, and adult dogs with normal or impaired renal function, with the histopathological appearance of kidneys from age- and size-matched normal dogs.
There were fewer glomeruli per unit area of cortex in kidneys from affected neonatal kidneys (P<0.05), increased numbers of fetal glomeruli in affected puppy kidneys (P<0.05), and a separate population of glomeruli with larger renal corpuscles and glomerular tufts in kidneys from affected adult dogs with normal renal function (both P<0.0001) compared with normal dogs. Other histological features that are characteristic of human X-linked and autosomal recessive Alport syndrome and that were present included hypercellular glomeruli, occasional crescents, segmental and global glomerular sclerosis, periglomerular fibrosis, interstitial fibrosis without significant cellular infiltrates and cystic dilatation of Bowman's capsular space and tubules. In dogs with renal impairment, the tubular index was the best predictor of increased urinary protein:creatinine (r=0.92) compared with glomerular, interstitial and vascular indices (r=0.77, 0.88 and 0.81), and medullary fibrosis correlated best with serum creatinine (r=0.72, P=0.0002).
The demonstration in Bull terrier kidneys of fewer nephrons in neonates increased fetal glomeruli, and a separate population of glomeruli with larger corpuscles and tufts reflects the effects of the underlying genetic mutation that are first manifest antenatally. The major determinant of renal impairment in adult affected Bull terriers is, however, progressive tubulointerstitial damage after birth.
牛头梗遗传性肾炎是常染色体显性遗传性奥尔波特综合征的一种模型，因为患病犬具有特征性的分层肾小球基底膜，并表现出垂直的雄传雄疾病传播。
本研究比较了患肾功能正常或受损的牛头梗幼犬、幼崽和成年犬肾脏的组织病理学特征，以及年龄和大小匹配的正常犬肾脏的组织病理学表现。
与正常犬相比，患病幼犬肾脏单位皮质面积的肾小球数量较少（P<0.05），患病幼崽肾脏的胎儿型肾小球数量增加（P<0.05），而肾功能正常的患病成年犬肾脏中有一群独立的肾小球，其肾小体和肾小球丛较大（均P<0.0001）。其他存在的、人类X连锁和常染色体隐性遗传性奥尔波特综合征所特有的组织学特征包括肾小球细胞增多、偶尔出现新月体、节段性和全球性肾小球硬化、肾小球周围纤维化、无明显细胞浸润的间质纤维化以及鲍曼囊腔和肾小管的囊性扩张。在肾功能受损的犬中，与肾小球、间质和血管指数（r=0.77、0.88和0.81）相比，肾小管指数是尿蛋白：肌酐升高的最佳预测指标（r=0.92），髓质纤维化与血清肌酐的相关性最佳（r=0.72，P=0.0002）。
牛头梗肾脏中新生儿期肾单位较少、胎儿型肾小球增加以及有一群独立的肾小体和肾小球丛较大，这表明潜在基因突变的影响在出生前就已首次显现。然而，成年患病牛头梗肾功能损害的主要决定因素是出生后进行性的肾小管间质损伤。
