Noh J W, Wiggins R, Phan S H
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0602.
Nephron. 1993;63(1):73-8. doi: 10.1159/000187146.
Crescentic nephritis was induced in rabbits by injection of antirabbit glomerular basement membrane (GBM) antibodies. Urine samples were obtained by catheterization and assayed for transforming growth factor-beta (TGF-beta) activity. On day 31, all animals were sacrificed for evaluation of renal cortical histopathology and collagen content. The results show that control rabbit urine contains measurable amounts of TGF-beta. Urine TGF-beta activity was expressed in relation to urine creatinine concentration to correct for variation in urine concentration. When expressed in this manner, urine TGF-beta activity increased from day 2 onwards, peaked on day 7 and returned to normal levels after day 14. This time course is identical to that previously seen for the cortical and glomerular production of TGF-beta in the same model. Furthermore, when the normalized TGF-beta values for each animal were compared to their respective fibrosis parameters on day 31, significant correlations were observed for the values of urine TGF-beta activities on day 7 and all indices of fibrosis. These results suggest that measurements of urine TGF-beta activity at certain critical stages of disease could be useful in predicting the progression to end-stage renal disease with fibrosis and might serve as a helpful noninvasive adjunct in monitoring response to therapy.
通过注射抗兔肾小球基底膜(GBM)抗体在兔体内诱发新月体性肾炎。通过导尿获取尿液样本,并检测转化生长因子-β(TGF-β)活性。在第31天,处死所有动物以评估肾皮质组织病理学和胶原含量。结果显示,对照兔尿液中含有可测量的TGF-β。尿液TGF-β活性以与尿肌酐浓度相关的方式表示,以校正尿液浓度的变化。以这种方式表示时,尿液TGF-β活性从第2天开始增加,在第7天达到峰值,并在第14天后恢复到正常水平。这个时间进程与之前在同一模型中观察到的皮质和肾小球TGF-β产生的时间进程相同。此外,当将每只动物在第31天的标准化TGF-β值与其各自的纤维化参数进行比较时,观察到第7天的尿液TGF-β活性值与所有纤维化指标之间存在显著相关性。这些结果表明,在疾病的某些关键阶段测量尿液TGF-β活性可能有助于预测向终末期肾病伴纤维化的进展,并且可能作为监测治疗反应的有用的非侵入性辅助手段。