Urine Transforming Growth Factor-β Activity is Related to the Degree of Scarring in Crescentic Nephritis in the Rabbit

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Abstract
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-β (TGF-β) 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-β. Urine TGF-β activity was expressed in relation to urine creatinine concentration to correct for variation in urine concentration. When expressed in this manner, urine TGF-β 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-β in the same model. Furthermore, when the normalized TGF-β values for each animal were compared to their respective fibrosis parameters on day 31, significant correlations were observed for the values of urine TGF-β activities on day 7 and all indices of fibrosis. These results suggest that measurements of urine TGF-β 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.

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