Role of proteinases in renal hypertrophy and matrix accumulation

Graded compensatory renal growth was induced either by unilateral (UNX) or 5/6 nephrectomy (5/6-NX). Over the experimental period of 16 weeks, kidney weight increased by 59% in SHAM animals, while the remaining kidney in UNX rats more than doubled its initial weight. The hypertrophic response was most pronounced in the remnant kidney after 5/6-NX with a four fold increment in kidney weight. Morphologically glomerular volume increased moderately after UNX (+27%), while 5/6-NX was associated with marked glomerular hypertrophy (+87%). Significant focal sclerosis was found in 11% of glomeruli in the remaining kidney after UNX. By contrast 83% of glomeruli wre sclerosed in the remnant kidney after 5/6-NX. In parallel, there was a significant increase in the glomerular protein/DNA ratio (+23%) in 5/6-NX but not in UNX animals. These glomerular alterations were associated with lower glomerular cysteine and metalloproteinase activities (collagenase, -57%; gelatinase, -49%) in 5/6-NX rats, while UNX rats had normal glomerular proteinase activities. In terms of tubular proteinases, cathepsin activities were significantly lower in UNX rats (cath. L+B, -38%; cath. B, -37%; cath. H, -27%) and more so after 5/6-nephrectomy (cath. L+B, -72%; cath. B, -73%; cath. H, -73%), while metalloproteinase activities were only reduced in 5/6-NX rats (collagenase, -35%; gelatinase, -58%). These findings demonstrate that kidney hypertrophy is associated with reduction in renal proteinase activities.(ABSTRACT TRUNCATED AT 250 WORDS)