Hengtrakul Nuttha, Furrow Eva, Borofsky Michael, Toth Ferenc, Lulich Jody P
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota, USA.
Department of Urology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
J Vet Intern Med. 2025 Jan-Feb;39(1):e17278. doi: 10.1111/jvim.17278.
Nephrocalcinosis is a common pathological finding in cats with chronic kidney disease and nephrolithiasis. Understanding its pathogenesis may identify future therapeutic targets.
Nephrocalcinosis is associated with expression of an osteogenic phenotype.
Kidneys with medullary mineralization were obtained from 18 cats (10 with and 8 without nephroliths) undergoing necropsy.
Cross-sectional study. Microradiography and histopathology (modified von Kossa stain) were used to confirm parenchymal mineralization. Immunohistochemistry for 5 osteogenic markers was performed to determine their co-localization with nephrocalcinosis. The proportion of kidneys with stronger immunointensity in mineralized versus non-mineralized regions was analyzed using 1-tailed sign tests. The proportion of kidneys with co-localization of nephrocalcinosis and each marker was compared between kidneys with and without nephroliths using Fisher's exact tests.
Nephrocalcinosis co-localized with osteopontin immunoreactivity in all 18 cats (100%) and with osteocalcin in 12 cats (67%). Both osteogenic markers had stronger immunointensity in mineralized regions compared with non-mineralized regions. Limited co-localization was observed with other markers: bone morphogenic protein-2 in 2 kidneys (both with nephroliths) and tissue non-specific alkaline phosphatase in 1 kidney (without nephroliths); runt-related transcription factor-2 was undetected. No statistically significant differences were found in the co-localization of nephrocalcinosis with osteogenic proteins between kidneys with and without nephroliths.
Expression of osteogenic proteins in areas of nephrocalcinosis indicates that nephrocalcinosis is associated with the development of an osteogenic phenotype. Targeting these processes could offer a novel approach to prevent nephrolithiasis at its origin.
肾钙质沉着症是患有慢性肾病和肾结石的猫常见的病理表现。了解其发病机制可能有助于确定未来的治疗靶点。
肾钙质沉着症与成骨表型的表达有关。
从18只接受尸检的猫（10只患有肾结石，8只未患肾结石）获取有髓质矿化的肾脏。
横断面研究。使用微射线照相术和组织病理学（改良冯科萨染色）来确认实质矿化。对5种成骨标志物进行免疫组织化学检测，以确定它们与肾钙质沉着症的共定位情况。使用单尾符号检验分析矿化区域与非矿化区域免疫强度更强的肾脏比例。使用费舍尔精确检验比较有肾结石和无肾结石的肾脏中肾钙质沉着症与每种标志物共定位的比例。
在所有18只猫（100%）中，肾钙质沉着症与骨桥蛋白免疫反应性共定位，在12只猫（67%）中与骨钙素共定位。与非矿化区域相比，两种成骨标志物在矿化区域的免疫强度更强。与其他标志物的共定位有限：2只肾脏（均患有肾结石）中有骨形态发生蛋白-2，1只肾脏（未患肾结石）中有组织非特异性碱性磷酸酶；未检测到 runt 相关转录因子-2。有肾结石和无肾结石的肾脏中，肾钙质沉着症与成骨蛋白的共定位无统计学显著差异。
肾钙质沉着症区域中成骨蛋白的表达表明肾钙质沉着症与成骨表型的发展有关。针对这些过程可能提供一种从源头上预防肾结石的新方法。
