RENAL BIOPSY COLLAGEN-I MESSENGER-RNA PREDICTS SCARRING IN RABBIT ANTI-GBM DISEASE - COMPARISON WITH CONVENTIONAL MEASURES

Progressive loss of normal structure associated with scarring is the h allmark of chronic diseases of most organs. To test the hypothesis tha t measurement of interstitial collagen mRNA levels would be a useful i ndex to predict future scarring, we developed an assay to quantitate a lpha 1(I) procollagen mRNA factored for GAPDH mRNA using RT-PCR (the ' 'CI:G ratio''). We first defined conditions under which the assay coul d be used for analysis of renal biopsy samples. The CI:G ratio was the n used to determine whether mRNA measurements performed at an early st age of inflammation (day 7) in a model of anti-GBM disease in the rabb it would predict outcome at day 30 as measured by interstitial and glo merular scarring and renal cortical hydroxyproline accumulation. The p redictive value of this assay was compared to functional (serum creati nine and urine protein:creatinine ratio) and histologic (glomerular an d interstitial scoring) parameters also measured at day 7. We found th at the CI:G ratio alone provided a sensitive and discriminating assay over a wide range of renal injury that predicted various parameters of scarring with an average coefficient of determination (r(2)) of 0.69. This predictive power was higher than that found for conventional mea sures, which tended to have good discriminatory capacity over limited ranges of renal injury. The CI:G ratio provided significant additional predictive power over and above that available from combinations of c onventional functional or histologic parameters. We conclude that meas urement of the CI:G ratio in biopsy samples deserves further assessmen t as a potentially useful quantitative predictor of outcome that could lead to improved clinical decision-making.